Adisseo

HOW CAN WE MAXIMISE BUTYRATE EFFICACY?

To profit from butyrate supplementation, the molecule needs to be at the right place and in the right quantity. In this second article of three, we explain why precision delivery is so important to maximise butyrate efficacy.

When butyrate is added to the diet, it triggers several beneficial effects in the digestive tract of animals (as described in our first article). There are different forms on the market, based on distinct production processes. In animal feed, butyrate salts or butyrins are used.

  • Butyrate salts: Available in the form of pure butyrate salts (powders or in a granulated form) or with a coating. Different processing techniques influence the level of odour and the target release capabilities of the butyrate.
  • Butyrins (glycerides of butyric acid): Butyrins are molecules where 1, 2 or 3 butyrate side chains are bound to a glycerol backbone, forming mono-, di- or triglycerides, respectively. They are liquids with a reduced odour, compared to pure butyrate, and can be put onto a silica carrier to create a dry product.

Target delivery of butyrate

As butyrate can trigger different mechanisms throughout the entire digestive tract, it is of paramount importance to study how this molecule can be delivered in specific intestinal segments, and what the consequences of different release profiles are.

It is indeed essential that butyrate is released along the intestinal tract for it to express its full potential. However, butyrate is a small molecule that is easily absorbed and metabolised in the first part of the digestive tract, the stomach. This not only reduces the bioavailability of the product further in the gut, but can also induce an inflammation and/or a dysbiotic response in some cases.

Two main approaches have been developed to tackle the challenge of enteric butyrate delivery: the use of butyrate derivatives such as butyrins and the coating of butyrate.

In the case of butyrins, the lipase, secreted from the pancreas into the first part of the intestine, will cleave the bonds on the outside of the glycerol molecule, resulting in a target release response, mainly in the first part of the small intestine (Figure 1).
Butyrate salts are often further processed with encapsulation techniques such as spray-cooling/chilling, to give embed the molecule in a protective matrix.

  • A coating supports a target release (precision) delivery of the butyrate along the whole digestive tract, including lower gut.
  • A coating reduces the unpleasant odour of butyrate, hence improving handling specifications.

The coating of most commercial butyrate salts is in the form of a protective fat matrix – usually hydrogenated palm oil. This fat-coating makes sure that most of the butyrate salt content will only be released once the lipase will break down the fat.

Figure 1 – Lipase, secreted by the pancreas, will break down the protective fat matrix of coated butyrate, and two butyrate side chains of tributyrin. Both mechanisms result in intestinal butyrate release.

Not all coatings are equal

The value of butyrate products is determined by its capacity to delivery butyrate critical gut regions, rather than its butyrate concentration. However, we found that the coatings of different commercial butyrate products vary greatly in quality, which has a profound effect on their release characteristics. New techniques are available to better assess the quality of the coating (see box below).

Do you see the cracks and holes in the coating with the human eye?

An experiment showed that while fat coated butyrate products might look the same on paper, they can differ when you zoom in. Differences can be caused by the raw material used and/or production settings (e.g., speed of mixing) employed.

At the experimental facilities of Capsulae (France), two different prototypes of butyrate salts with the same composition (30% sodium butyrate embedded in a 70% hydrogenated palm fat-based protective matrix) were analysed using electron microscopy (EM) imaging and in vitro digestion assays.

This experiment showed that, when zooming in on the molecule after incubation in acid (to mimic the digestion process), the two prototypes showed:

  1. Differences in pores and cracks in the surface of the particle and number and size of holes on the inside of the particle. This influences the protective properties of the fat coating.
  2. Differences in resilience to gastric conditions, shown by differences in the amount of butyrate released during the first incubation step between the two prototypes. This has an effect on the quality of target (precision) release of the butyrate.

These differences are hard to spot with the human eye, but are crucial for quality of the end product, product performance and customer satisfaction.

Do you see the cracks and holes in the coating with the human eye?

Maximising performance with Adimix Precision

Adimix Precision is a precision delivery coated butyrate salt, developed by Adisseo. The functional superiority and differences in protective characteristics of Adimix Precision, compared to other coated butyrate products are the result of the following:

→ Optimised spray-cooling coating techniques

Adimix Precision is embedded in a special coating, applied using spray-cooling techniques. As pioneers in butyrate coating, Adisseo products have benefitted from a long initial optimisation process.

The coating protocol was adjusted based on the characteristics of the sodium butyrate produced in Adisseo’s factory, resulting in functional superiority and differences in protective features compared with other coated butyrate products on the market.

→ High Target Release Capacity

The variety in capacity between different products is measured by Adisseo using the Target Release Capacity (TRC). The TRC is the amount of butyrate that still can be detected in the product after in vitro incubation mimicking gastric conditions. As such, the TRC is an estimate of the relative amount of butyrate that is protected from gastric absorption and that has the capacity to be target-released in the intestinal tract.

A product with a high TRC can trigger more beneficial gut health effects in animals, compared to products with a low TRC. In comparative evaluations, the TRC values of Adimix Precision were higher than most chemically similar fat-coated butyrate products.

→ High Stability during processing

Adimix Precision has been shown to be very stable during feed processing, with butyrate recovery values higher than 95% after pelleting, both at moderate and high temperatures. The product’s recovery was at least 84% following both extrusion and expansion.
This superior stability enables Adimix Precision to act in all parts of the gut, even after feed processing. Trials in broilers showed a higher butyrate concentration in the caecal contents with the Adimix Precision supplemented in pelleted feed, compared to unprotected butyrate and tributyrin.

Conclusion

Different commercial butyrate products liberate butyrate in different parts of the digestive tract. This has an important impact on their functionality. In the case of butyrate, it is essential that butyrate is released in regions in the digestive tract where it can be most most effective, for it to express its full potential. And this is exactly what Adimix Precision does. In the next article we delve into more trials that confirm the efficacy of Adimix Precision.

 

Learn more about the benefits of precision delivery in the comprehensive technical booklet

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Booklet

3 reasons why you should be using butyrate in pig and poultry diets

Butyrate is a molecule with high potential for humans and animals. In this first article of three, we explain what butyrate is and give three solid reasons why it is a crucial element in pig and poultry diets.

Butyric acid is a short-chain fatty acid that is naturally produced in the hindgut of monogastrics and the rumen of ruminants. It has the potential to trigger several beneficial effects in the digestive tract of humans and animals.

In humans, butyrate has been studied as a tool in the prevention and treatment of inflammatory bowel diseases and colon cancer. In animal production, butyrate is added to the feed to improve the digestive tract development and maintenance, which is crucial to prevent disturbances linked to the challenges faced by the animals. This purpose of prevention makes it a perfect fit in today’s approach to animal production and diet formulation.

Butyric acid itself is a volatile and corrosive liquid, with a very pungent smell and is therefore very rarely applied in animal feed in this form. This is one of the reasons why derivatives of butyric acids are used, most commonly salts (coated butyrates) and glycerides (butyrins). Innovations made over the years in coated butyrate products have increased precision delivery of the molecule, enhanced product stability and reduced odor associated with the product.

Here are 3 reasons why the momentum is right to start using butyrate:

1. Butyrate improves gut health

A healthy gastrointestinal system (gut) is important for animals to achieve their maximum production potential, to increase feed efficiency and prevent intestinal infections and disease. And this is especially important for young animals, where the digestive tract is immature and not all feed ingredients can be digested well.

Butyrate promotes gut health in different ways, such as:

  • Butyrate stimulates cell renewal and differentiation of the cells of the intestinal wall (the enterocytes). This will increase gut barrier function and gut integrity and promote mucosal healing; all needed for an efficient absorption of nutrients from the diet and to prevent gut wall infections.
  • Butyrate modulates the thickness of the mucus layer of the intestinal wall. A healthy mucus layer forms a protective barrier between the underlying epithelium and the lumen containing toxins and bacteria amongst others.
  • Butyrate is a regulator and a key signaling molecule of the intestinal microbiome. It improves beneficial bacterial populations (such as Lactobacilli and Bifidobacteria) and reduces the colonization of harmful bacteria (such as Salmonella, Campylobacter and E. coli) in the digestive tract of animals. More beneficial bacteria means less chance for the pathogenic ones to proliferate and cause infections or disease.
  • Butyrate increases the villus height to crypt depth ratio. This increased ratio leads to increased absorptive capacity of the intestinal wall, which will benefit nutrient digestibility and optimized nutrient utilization (for e.g. proteins). In addition, butyrate stimulates the release of digestive enzymes, needed for optimum nutrient digestibility and feed efficiency.

2. Butyrate helps the immune system

A strong immune system in farm animals is important to prevent diseases (and antibiotic use), animal welfare and to reach the animal’s full genetic potential. The gut is an organ that has the most immune cells in the body (approximately 70%) and is part of the first line of active defense against pathogens.

Butyrate promotes the immune system in different ways, such as:

  • Butyrate reduces a range of pro-inflammatory cytokines (through the inhibition of the so-called nuclear factor kappa B (NF-κB) pathway). Reducing these types of cytokines helps to reduce the damage caused by oxidative stress and inflammation.
  • Butyrate increases anti-inflammatory cytokines (such as interleukin-10). Butyrate also modulates lymphocyte proliferation and macrophage activity and activation and stimulates the secretion of antibodies. These positive effects of butyrate will prevent oxidative stress and inflammation and create a faster and stronger immune response.
  • Butyrate is an inducer of the enzyme intestinal alkaline phosphatase (IAP). This enzyme is a potent anti-inflammatory enzyme that removes a phosphate group from toxic products such lipopolysaccharide (LPS) or endotoxins that are present in the gut. This will stop inflammation cascade and the release of inflammatory cytokines.

3. Butyrate suppresses intestinal Salmonella and Campylobacter growth

Worldwide there is increased consumer and governmental focus on food safety. The European Union for example has set clear targets to combat Salmonella. Strict regulations have been implemented, which have brought added costs to control and monitoring programs for animal production.

Livestock producers are trying to control Salmonella load on-farm in order to reduce (cross-) contamination in slaughterhouses, thereby decreasing the risk to humans. Besides biosecurity measures and vaccination programs, producers are using feed additives as part of a holistic control program.

Butyrate helps to control Salmonella in different ways, such as:

  • Butyrate can down regulate Salmonella virulence, both by direct effects on virulence gene expression and by modulating activity of host cells. Studies have shown that precision-delivery coated butyrate is able to decrease Salmonella or Campylobacter colonization in broilers and swine.
  • Butyrate triggers the expression and secretion of antimicrobial host defense peptides in the digestive tract of animals, thereby limiting the growth of several enteric bacterial genera, including Salmonella.

Conclusion

The focus on and research around gut health in farm animals has accelerated in the last few years, due to stricter regulation on antibiotic use and the ban on therapeutic levels of zinc oxide in swine diets amongst others. Butyrate has the capacity to positively trigger different mechanisms in the gut of monogastrics. A healthy gut – in turn – is a prerequisite to improvements in growth, performance, feed efficiency and animal health.

 

Learn more about butyric acid and
butyrate in the technical booklet

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Booklet

ADIMIX PRECISION: LARGE BODY OF TRIAL DATA CONFIRMS VALUE FOR MONEY

Different commercial protected butyrate products liberate butyrate in different parts of the digestive tract. This has an important impact on their functionality. The efficacy and performance of Adimix Precision has been confirmed in many trials and clearly shows its premium position in the market.

Butyrate is a molecule with high potential for farm animals and thus part of the nutritional toolbox to help producers cope with challenges, ranging from tight margins to antibiotic reduction and complying with food safety measures.

The most value for money

Like with any feed additive and with the current high feed prices, you want to make sure that the product does what it is supposed to do. Adimix Precision is a precision delivery coated butyrate salt, developed by Adisseo and produced in the company’s own facilities. It is based on many years of expertise and knowledge on butyrate production. Because of its high target release capacity, this protected butyrate brings the most value for money for poultry and pig producers. This is reflected in:

  • Intestinal function and nutrient utilisation. Adimix Precision has a positive effect on the microbiota, gut barrier and immunity, all ingredients for a healthy working gut and good digestion and uptake of nutrients.
  • Food safety. Adimix Precision participates in the reduction of the risk of Campylobacter and Salmonella contamination, two important zoonotic bacteria to prevent throughout the whole production chain of pigs and poultry products.
  • Animal resilience to deal with challenges. Adimix Precision helps to overcome intestinal damage caused by bacterial, viral, parasites and toxins challenges.

Reliable and predictable results

Adisseo has performed a large number of trials to confirm the results of Adimix Precision related to zootechnical performance and food safety issues. Here we discuss a few of the major effects shown in poultry and pigs.

POULTRY

Young animal nutrition is key. Adding protected butyrate to the starter diet (day 0-14) increases bird performance. Adimix Precision showed:

  • Significant higher body weight at day 7 and day 14
  • Improved FCR at day 42
  • Better intestinal developments

In a meta-analysis of 62 trials, protected and unprotected butyrate were compared under challenging conditions. In broilers, Adimix Precision showed:

  • Higher average daily gain (+4%), without significantly affecting the feed intake (+0.6%).
  • Lower FCR (-3%)

In a trial with 1,440 broilers, protected butyrate was compared with antibiotic growth promoters during an E. coli challenge. At day 42, Adimix Precision showed:

  • Higher final weights (+6.1% vs control, +7.5%vs Bacitracin, +5.7% vs Halquinol)
  • Lower FCR (- 7.5% vs control, -8.4% vs BMD and vs Halquinol)

Can we reduce performance losses when soybean meal is exchanged by rapeseed meal (RPM)? Adding Adimix Precision to a RPM diet showed:

  • Significant increase in body weight gain and FCR
  • Greater duodenal villus height: crypt depth ratio

In a trial with 50 one-day old chicks, the effect on protected butyrate was evaluated on Salmonella enteritidis shedding after inoculation of the bacteria, compared to adding no butyrate to the diet. Adimix Precision showed:

  • Almost half the number of positive Salmonella test results, compared to the control group (48% against 97%) at day 20
  • Significant drop of positive Salmonella test results, compared to the control group (6% against 36%) at day of slaughter (day 42)

Follow up trials confirmed that coated butyrate induces a beneficial shift in hindgut microbiota composition, compared to unprotected butyrate or no butyrate at all. Adimix Precision showed:

  • Higher Firmicutes:Proteobacteria ratio
  • Increased relative abundance of beneficial butyrate-producing Lachnospiraceae + Ruminococcaceae
  • Lower levels of potentially harmful Enterobacteriaceae
  • Higher resilience against Salmonella colonisation in the gut

In two trials, it was further investigated whether caecal Campylobacter colonisation can be reduced in broilers using coated butyrate at different inclusion levels. Adimix Precision showed:

  • Significant reduction of Campylobacter caecal counts at day 29 and 39 for both inclusion rates (3g/t and 5g/t)
  • Strong reduction in caecal Campylobacter counts when coated butyrate is fed throughout the whole life of the bird (from day 1 to day 39)

In a trial with 800 birds, the zootechnical and intestinal health promoting effects of coated butyrate was evaluated during a subclinical (without mortality) necrotic enteritis (NE) model with Clostridium perfringens. Compared to unsupplemented group, Adimix Precision showed:

  • Reduction of number of lesion scores 2 and 3 on day 21
  • Increase of number of birds with zero lesion scores at day 28
  • Higher final live weights
  • Better feed intake, FCR and EPEF

PIGS

The sow’s diet is of utmost importance, as she needs enough nutrients for maintenance, milk production and piglet growth. A trial looked at the effect of adding protected butyrate or unprotected butyrate to the sow diet. Adimix Precision showed:

  • Positive effect on feed intake sows, shown in maintained weight during lactation
  • Heavier piglets at birth and at weaning
  • Higher IgG and IgA levels in colostrum

A trial with 300 high-health grower pigs looked at the effect of protected butyrate on performance and carcass characteristics in grower and finisher pigs. Pigs received either a diet with an antibiotic growth promoter (AGP) or not. Adimix Precision showed:

  • Highest carcass weight
  • Improved final weight and FCR, both with or without AGP
  • Increased profits for swine producers (ROI between 8:1 and 20:1)

A meta-analysis of 52 trials evaluated the effect of protected and unprotected butyrate under, both standard and challenging, conditions. Adimix Precision showed:

  • Increased ADG (+24%) at day 14 post weaning
  • Improved FCR and feed average daily feed intake

In a trial with pigs from different ages, the effect on protected butyrate was evaluated on Salmonella, and in particular the Sample-to-Positive (S/P) ratio. Adimix Precision showed:

  • Consecutive low S/P values (lower than 0.6, meaning the farm is not in the risk status)

To prevent the spread of PEDv, the virus that causes porcine epidemic diarrhoea, a trial was set up to evaluate the effect of protected butyrate on piglets and sows that were infected with the virus. Compared to no butyrate supplementation, Adimix Precision showed:

  • More viable offspring
  • Havier piglets from day 14 onwards

Can protected butyrate further increase the post weaning performance of piglets that receive a diet with organic acids? A trial with 383 Duroc piglets showed that Adimix Precision:

  • Improved growth rates of weaned piglets, on top of organic acid supplementation (biggest effect for youngest and smallest piglets)
  • Improved daily feed intake levels

Conclusion

Pig and poultry producers are continuously seeking to improve performance and use less medication, while they also face increasing pressure to increase food safety measures and deal with tight margins. Different commercial butyrate products are available on the market to help producers with these challenges. However, the value for money can be quite different between them. Adimix Precision is the result of Adisseo’s expertise on butyrate production and years of fine-tuning of the production process and a large number of trials.

This protected form of butyrate is released along the whole digestive tract, and especially in the hind gut, for it to express its full potential. Using Adimix Precision helps to gain control over animal performance, young animal development, gut health and bacterial colonisation. All of this has positive effects on animal health, farm profitability, margins, dependence on antibiotics and food safety.

Learn more about the details of the trials in the comprehensive technical booklet

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Booklet

SANACORE® GM FOR GUT INTEGRITY AND PROTECTION AGAINST THE INTESTINAL MYXOSPOREAN ENDOPARASITE ENTEROMYXUM LEEI

Gut health is a fundamental element for the optimal growth and performance of cultured fish, while it is inextricably linked with the health of the entire organism. Temperature shifts, high stocking densities, transport, handling and the increasing inclusion of plant-based ingredients in diets may contribute to the disruption of gut integrity and trigger chronic inflammation which synergistically undermine performance and pave the way for opportunistic pathogens. Enteromyxum leei, an endoparasite which colonizes the intestine, is a case in point which is typically illustrated with anorexia, weight loss, muscle reduction and eventually death.

The present article demonstrates the efficacy of SANACORE® GM, a broad spectrum health-promoting additive, on supporting gut integrity, eliciting anti-inflammatory activity and protecting the fish from the infestation of E. leei.

 

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Adisseo announces the laureates of the first Adisseo Research Grant (2021-2024).

Selenium and immunity: food for thought

Banner Selenium and immunity: food for thought

A balanced diet is key for human health promotion. Among essential nutrients Selenium is shown to be deficient in many countries worldwide.

In animals as well as in humans, Selenium deficiency is associated with a compromised immunity and increased susceptibility to various diseases including the recent epidemic caused by COVID 19.

Production of Se-enriched eggs, meat and milk could be an important approach to deal with human Selenium deficiency.

 

Prof Peter SURAI

Prof Peter SURAI
Feed-Food Ldt, UK

Dr. Michele DE MARCO

Dr. Michele DE MARCO
GlobalScientific and Technical Manager
ADISSEO

 

Introduction

Many centuries ago, Hippocrates’ observations on the relationship between health and nutrition led to the beginning of a discussion about the factors that influence our health.

However, over the last few decades, it has become obvious that although our lifestyle, with reference to our diet, stress, smoking, medical attention, exercise and genetics, is a major determinant of our health status, our diets also play a pivotal role. Nutritional practices in most developed countries have recently changed the focus from fighting nutrient deficiencies to addressing nutrient requirements in order to maintain good health throughout ones’ life.

However, people do not all consume the same food, and they meet their nutritional needs in many and various ways. Food is the major source of micronutrients and natural antioxidants, including vitamin E, vitamin C, carotenoids, flavonoids, selenium (Se), etc.

It is necessary to take into account that all antioxidants in the body play very important functions and are key to maintaining the redox balance of the body, to preventing oxidative stress and to maintaining good health status, all of which help to prevent disease.

The main antioxidants in the body work as a “team”, which is responsible for antioxidant defense.

In this team, which is better known as the antioxidant system, Se, in the form of selenoproteins, plays a pivotal role and has been defined as the “chief executive” of antioxidant defense.

Global Se deficiencies & human Se requirements

Deficiencies of micronutrients, including essential trace elements, affect up to 3 billion people worldwide.

The dietary availability of trace elements is determined to a great extent by their soil concentrations. One such micronutrient is Se, and up to 1 in 7 people are affected by an inadequate dietary intake of Se, which is also known to affect the health of livestock.

The main problem with Se nutrition is the great variability of Se concentrations in various foods, which is directly correlated to the Se concentration in the soil where crops and vegetables are grown, and livestock are raised.

Furthermore, the availability of Se to plants depends on many factors, including the soil pH, the oxidation-reduction potential and the mineral composition of the soil, the artificial fertilization rate and rainfall. Since the Se content in plant and animal-based feeds depends on its availability in the soil, the level of this element in human foods varies to a great extent from region to region.

In this regard, higher levels of rainfall and lower soil pH have been predicted, due to the ongoing climate change, thereby increasing the likelihood of a poor Se status for both livestock and humans.

A climate change projection has recently predicted future global Se soil losses in which 66% of croplands could lose up to 8.7% of Se. These losses will further increase the worldwide deficiency of Se.

The World Health Organization (WHO), USDA and EFSA have recommended a human dietary intake of Se of 55–85 μg/day for adults (the EU Recommended Dietary Allowance – RDA of Se is 55 μg/day, while the USA RDA varies from 55 up to 70 μg/day for various categories of people;.

Selenium deficiency and a low daily Se dietary intake can cause endemic diseases or other significant environmental health problems, such as Keshan disease (a degenerative heart disease frequently observed in Keshan, China) and Kaschin–Beck disease (a form of osteoarthropathy that causes deformity of the joints). The daily dietary intake rate of Se varies considerably between countries/regions.

Se deficiency has been reported in parts of China (Keshan disease areas), Saudi Arabia, the Czech Republic, Burundi, New Guinea, Nepal, Croatia and Egypt for daily Se intake rates <30 μg/day.

In addition, many other countries, such as India, Belgium, Brazil, the UK, France, Serbia, Slovenia, Turkey, Poland, Sweden, Germany, Spain, Portugal, Denmark, Slovakia, Greece, the Netherlands, Italy, China, Austria and Ireland, have been identified as having Se deficient areas, because the daily Se intake levels are below the WHO recommended amount of 55 μg/day.

About 76% of the countries throughout the world are located in Se-deficiency regions, where the daily Se intake level is lower than 55 μg/day for adults.

Negative effect of Se deficiency on human health

Selenium is an essential element for humans and animals in order to have adequate bodily functions.

The beneficial effects of Se on health are well known, and they include the protection of body tissues against oxidative stress, the maintenance of defense against infection by modulating the immune and inflammatory responses of the body, the modulation of growth and development, as well as having possible anti-carcinogenic properties.

Se deficiency is associated with a decreased expression of various selenoproteins in human tissues, which in turn affects the major metabolic processes, including antioxidant defense and redox homeostasis, and these are major factors that are involved in the immunocompetence and prevention of different diseases.

Therefore, an extreme Se deficiency is associated with the development of Keshan disease and Kashin-Beck disease. Furthermore, a low Se status of the general population is believed to increase the risk of developing cancer, cardiovascular disease (CVD), Alzheimer’s, cognitive decline/dementia, thyroid autoimmune disease, problematic fertility/reproduction, rheumatoid arthritis and a variety of other diseases.

An insufficient dietary selenium intake has also been shown to impair immune competency, to reduce defense against various viral and bacterial diseases and to diminish the resistance to toxic heavy metals.

Selenium and immunity

The information that has been accumulated actively over the last 20 years indicates that Se is among the major immunomodulating agents.

Selenium affects all the components of the immune system, including the development and expression of natural nonspecific and specific humoral and cell-mediated responses.

In general, a deficiency in Se appears to result in immunosuppression, whereas an optimal Se supplementation appears to result in augmentation and/or restoration of the immunologic functions.

In fact, a deficiency in Se has been shown to inhibit resistance to microbial and viral infections, to compromise the neutrophil function, antibody production, and the proliferation of T and B lymphocytes in response to mitogens, and cytodestruction from T lymphocytes and NK cells.

The relationship between nutrition and viral infection has also been studied.

It seems likely that a deficiency in Se could be an important factor in the increased susceptibility of animals and humans to viral and bacterial diseases.

Indeed, as a result of Se deficiency, the consequent high production of reactive oxygen species (ROS) and increased oxidative stress of a host can lead to an increased virus mutation rate ( Figure 1), which in turn can result in the emergence of viral pathogens with new pathogenic properties.

Therefore, Se deficiency is associated with a mutation of the viral genotype, whereby a virus can be converted from a benign strain to a highly virulent one.

Such RNA viral mutations have been reported to be faster and longer-lived in Se-deficient individuals than in healthy ones both in animals and humans.

Figure 1

Figure 1. Effects of Se on viral diseases

As mentioned above, viral infections normally compromise antioxidant defense by simultaneously increasing the generation of ROS with downregulation of the biosynthesis of antioxidant enzymes in the infected cell.

Some of the viruses that are associated with ROS production are the human immunodeficiency virus (HIV), the hepatitis B virus (HBV), the hepatitis C virus (HCV), the Epstein-Barr virus (EBV), herpes simplex virus type 1 (HSV-1), the vesicular stomatitis virus (VSV), the respiratory syncytial virus (RSV), human T cell leukaemia virus type 1 (HTLV-1) and influenza viruses.

Immune responses are intimately linked to inflammatory processes, and these in turn are inter-related to the production of ROS and redox control processes.

Furthermore, viral infections are often correlated with macronutrient and micronutrient deficiencies.

In fact, a selenium deficiency is common among patients infected with viruses.

For example, ROS production can increase the expression of inflammatory cytokines through an increased NF-κB activity, and it seems likely that Se modulates inflammatory and immune processes through redox functions.

An excessive body production of ROS causes damage of all biological molecules, including polyunsaturated fatty acids, proteins and DNA, thus causing protein aggregations and gene expressions errors.

For example, coxsackievirus is an enterovirus that causes Keshan disease.

Evidence suggests that Se supplementation could prevent the development of Keshan disease by enhancing viral immunity and by preventing genetic adaptations in the viral genomic RNA, which together result in a reduced virulence and cardiac pathology.

Heart damage has been observed in animal studies upon infection with a non-cardiovirulent strain of coxsackievirus B, albeit only in Se-deficient mice, whereas mice fed Se-adequate diets showed no evidence of such heart damage.

This deficiency was reflected in a higher viral load on the heart of the Se-deficient mice as well as in a lower antigen-specific T-cell response, compared to that of the Se-adequate littermates.

In fact, benign forms of both Coxsackievirus B3 (CVB3) and influenza virus type A can rapidly mutate to virulence in hosts with an Se-deficient status. Similarly, a recent study has demonstrated that Se supplementation in chickens challenged by a low pathogenicity avian influenza virus (H9N2) increases the expression of antiviral response genes, which can lead to a reduction of virus shedding from infected birds.

A large number of micronutrients in the diet, including Se, play a fundamental role in maintaining an “optimal” immune response. As a component of selenoproteins, Se is required for the effective functioning of the main immune cells, including neutrophils, macrophages, NK cells and T lymphocytes.

A high intake of selenium may help relieve oxidative stress and prevent an uncontrolled immune and inflammatory response.

An epidemic caused by a novel coronavirus (COVID-19 or SARS-CoV-2) belonging to the same group of β-coronaviruses as the severe acute respiratory syndrome (SARS) that appeared in 2002 and in the Middle East Respiratory Syndrome (MERS), is currently spreading throughout the world and threating human health and the world’s economy.

The occurrence, development, duration and severity of SARS-CoV-2 have been shown to depend on the interaction between the virus and the individual’s immune system.

SARS-CoV2, just like other RNA viruses [4], can probably trigger oxidative stress and this in turn leads to an elevated and uncontrolled production of ROS, which seems to cause a cytokine storm, that is, a deadly uncontrolled systemic inflammatory response resulting from the release of large amounts of pro-inflammatory cytokines and chemokines from immune effector cells during SARS-CoV2 infection, and with hyper inflammation in patients affected by SARS-CoV2.

As elderly people and people suffering from various diseases, including diabetes, hypertension and cardiovascular diseases, are already in a state of oxidative stress, such a viral infection will increase this stress, and this is one possible explanation of the severity of COVID-19 in these categories of patients.

At present, there is no effective treatment for SARS-CoV-2, but high immunocompetence is considered to be the most important contributor to decreasing the risk of this disease.

In this regard, an optimal nutritional status is of paramount importance and various nutritional deficiencies increase the risk of SARS-CoV-2.

In fact, a Se dietary deficiency is considered to be an important risk factor for SARS-CoV-2 infection and for the outcome of the therapies.

The effect of the Se status on the cure rates of COVID-19 has recently been shown in China. Indeed, a significant association between cure rate and background selenium status in cities outside Hubei (R2 = 0.72, F test P < 0.0001) has been reported.

Another similar study, carried out in Germany, reported that patients suffering from COVID-19 display a deficiency in the essential trace element Se in their blood, together with low concentrations of the Se transporter selenoprotein P (SELENOP) and low enzymatic activity of the secreted selenoprotein glutathione peroxidase 3 (GPx3).

This Se deficiency was found to be particularly marked in comparison with healthy European adults, and it was concordantly reflected in relatively depressed readings of all three of the different determined Se status biomarkers.

The observation that Se deficiency is more severe in the samples obtained from non-survivors than those from the survivors of COVID-19 may suggest some relevance of Se in coping with the virus and for a successful convalescence.

Strategies to deal with Se deficiency in the human diet: from farm to fork

Several potential options are available to improve the intake of selenium by humans.

These include direct supplementation, in tablet form (as inorganic salts, but the most common supplement uses high-Se yeast that contains SeMet and some other organic selenocompounds), soil fertilization, the supplementation of staple foods, such as flour, and the production of Se-enriched functional foods, such as Se-enriched eggs, meat and milk.

Several important factors should be considered when choosing the best food supplementation strategy for a given population.

In general, the main sources of dietary Se differ from country to country.

For example, in the UK, meat and meat products provide 32% of the required daily consumption of Se, and dairy products and eggs are responsible for 22% (Figure 2).

Figure 2

Figure 2. Estimated intake of Se from different foods in the UK in 1997.

On the other hand, about 50% of the Se in the diet in Russia originates from bread and cereals, while meat, milk and eggs provide about 20%, 10% and 5% of the daily Se consumption, respectively.

White bread, pork, chicken and eggs account for half of the Se in the diet in the USA. Meat and meat products (30%), bread and rolls (24%), fish/fish products (11%), and milk and yoghurt (9%) are the main contributors to the mean daily Se intake in Ireland.

Fish makes the largest contribution to dietary Se intake in alpine communities in Japan (48% of the daily total), and this is followed by eggs (24%) and meat (17%).

Fish accounts for 58% of the total daily Se intake in coastal communities, followed by meat (18%) and eggs (16%). In both districts, the total contribution of rice and wheat products is around 10%.

Among the animal-derived products, Se-enriched eggs are ideally suited to meet the daily requirements, as they are an important source of Se for the general population for the following reasons:

  • eggs are a traditional and affordable food in most countries and are consumed, more or less regularly, by people of all ages, without presenting social and religious obstacles;
  • they are a particularly safe vehicle for Se supplementation, given that a toxic dose of Se from eggs would require the consumption of more than 25 eggs per day over time, which is a highly unlikely situation;
  • options are available for the simultaneous enrichment of eggs with several important key nutrients, including omega-3 fatty acids, vitamin E and carotenoids;
  • generally speaking, with a single Se-enriched egg, it is normally possible to deliver (25-35 μg Se) i.e. around 50% of the human RDA for Se (55 to 70 μg Se/day).

Before the advent of commercially available organic selenium for animal diets, the main problem, as regards the enrichment of eggs with selenium, was the low transfer efficiency of inorganic selenium (the selenite or selenate forms) to the egg. In fact, even high doses of selenite in the diet of laying hens were not able to substantially enrich eggs with this trace element. It is interesting to note that practically all of the Se-enriched egg brands are produced using organic selenium as the major source of Se for laying hens at a level of 0.3-0.5 mg/kg in the feed.

Se-enriched eggs, as a rule, contain up to 30 µg Se per egg.

Since the maximum safe dietary Se intake (average NOAEL: ‘no observed adverse effect level’) is 819 µg, in order to have any detrimental effect from a Se overdose, it would be necessary to consume more than 25 eggs a day for a long period of time.

If we take into account the maximum safe dietary intake of Se identified by the Food and Nutrition Board (2000), that is, of 400 µg, it would be necessary for a person to consume 13 eggs a day for a long period of time, a situation that is difficult to imagine.

Fewer than one egg per day is generally consumed in most European and other developed countries, and the safety margin in such a condition is more than 10-fold.

Observations of Se-egg production in various countries indicate the following:

  1. The costs involved in Se-egg production do not normally exceed 2-5% of the total feed costs.
  2. An organic Se supplementation of laying hens is associated with the maintenance of a higher egg production in aging layers, better eggshell quality and internal egg quality (Haugh Units) as well as an improved FCR. These parameters pay money back and give profit at the level of 1:3-5. Therefore, the production technologies of “Se-enriched” products allow high-value end-products to be produced, which can be used as an effective promotion tool that translates into a free-of-charge investment for the producers.
  3. The additional inclusion of Se to already existing modified eggs (omega-3, vitamin E-enriched, iodine-enriched, etc.) can further enhance their quality and marketing potential, without any substantial increase in price.
  4. Labeling regulations differ substantially from country to country; however, a two-fold increase in Se content of eggs would fit the “Se-enriched” category of most countries.
  5. Some countries (e.g. Eastern European and Asian) allow claims to be made about the health benefit of Se, but in most areas it is only possible to put the level of Se on the label and give a comparison to the RDA. Even such a limited labeling would be a great advantage for producers.

There are great prospects of an increased production of Se eggs worldwide. However, an important limitation to the production of Se-eggs is a lack of public knowledge concerning the beneficial effects of Se in relation to animal and human health. Indeed, the companies that produce Se-eggs should invest more in educating the public in order to widen the market for Se-eggs.

Various types of meat (pork, beef and chicken meat), as well as milk and milk products are also important natural sources of Se in human nutrition. However, the Se concentration in meat varies substantially, depending on the geographical origin of the country and the Se supplements used. Indeed, it is well known that selenite or selenate dietary supplementation is not effective in increasing the Se concentration in meat, and only organic Se, in the form of SeMet, in the diets of chickens, pigs or cattle, can substantially increase the Se concentration in meat.

It has been shown that when organic Se is used at a dosage of 0.3-0.5 mg/kg in the diet of chickens, pigs and cattle, it is possible to produce meat containing at least 25-30 μg/g (100 g meat can provide >50% RDA). There is also substantial evidence that organic Se in the diets of dairy cows, goats and sheep can also help produce Se-enriched milk and milk products (milk powder, cheese, yoghurt etc).

Therefore, using organic Se in livestock diets offers a great opportunity of improving the Se status of the general population and of bringing it up to the RDA levels.

Indeed, most diets already contain at least 50% RDA selenium, and, the global problem of Se deficiency could be solved by adding eggs, meat or milk and milk products enriched with Se to the daily diets of people. This would help to improve the antioxidant status and immunocompetence of the general population and increase resistance to various pathogens/diseases. However, such benefits still require further support from medical institutes.

In conclusion, it should also be mentioned that the usage of organic Se in livestock diets would enhance the health of mankind as a whole, while, at the same time, lead to economic and welfare benefits in livestock production, in terms of a better animal disease resistance, improvement and/or maintenance of the productive and reproductive performances of animals reared under stressful commercial egg, meat and milk production conditions.

Moreover, there are also indications that product quality can also be improved, as a result of Se enrichment, in terms of quality traits, freshness and shelf-life.

Therefore, the organic Se concept in livestock production could become a holistic approach to avoid the risk of worldwide Se deficiencies and lead to different and diversified benefits being obtained from farm to fork, with free-of-charge investments.

Indeed, the diet cures more than the lancet.

Reference available upon request

 

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