If we learned anything from 2020, it is that we cannot control everything. For instance, we can’t control the weather, but we can work to control the mycotoxin risk it presents. Weather is the main influencing factor when it comes to mycotoxin risk, leading to a variation in risk levels across the U.S. This year is no exception to that trend, with mycotoxin levels having a wide distribution in the U.S. corn harvest. Mycotoxins can be responsible for the loss of production and efficiency in our animals — a duo we are not interested in.

What are mycotoxins?

Molds and fungi on crops naturally produce mycotoxins. Mycotoxins are ever-present on-farm but can vary in severity based on feed sources, storage and growing conditions. The three most common types of mycotoxins include Aspergillus, Fusarium and Penicillium. Aspergillus is responsible for aflatoxin B1, which can be more abundant with increased drought stress and dry field conditions. Trichothecenes and zearalenone are related to Fusarium. Trichothecenes are common field toxins in grain and silage, and swine are particularly impacted by this mycotoxin because they are considered a more sensitive species to deoxynivalenol (DON). T-2/HT-2 toxins and other trichothecenes are the most toxic for most species, while ochratoxins and citrinin are related to Penicillium. When an animal consumes mycotoxin-contaminated feed, there is risk of reduced production, immune suppression and decreased overall efficiency.

Learn more about mycotoxins at knowmycotoxins.com.

2020 Harvest Analysis

Dr. Max Hawkins, Alltech’s mycotoxin and harvest expert, presented his analysis, giving an insider’s view on this year’s crop, during the 2020 U.S. Harvest Analysis.

Crops are influenced by weather as we go through the growing season, leading to regionalized mycotoxin risk based on weather patterns. The Corn Belt had moderate to severe drought conditions throughout the growing season, in addition to wind-storms, which also affected corn crops. The Eastern U.S. saw above-normal rainfall on heat-stressed and dry crops. It should be noted that while the overall risk is normal this year, where the risk is high, it is notably high. These risks can be manageable if we are able to feed the average, which is why we need to do testing to evaluate what the potential maximum levels are.

Mycotoxin risk breakdown by species:

The 120 corn samples that were analyzed by Alltech 37+ contained an average of 5.9 mycotoxins per sample, with 50% of these samples considered moderate- to high-risk and 50% low-risk. While corn in general is relatively low-risk, pockets of high-risk samples could be an increasing concern with lower corn yields. If we are not able to be as selective when feeding corn, we may get into feeding higher-risk corn, or higher-risk feed ingredients may be used to compensate for less corn in the diet.

• Swine

The mycotoxin risk for sows is moderate to high, specifically related to DON and zearalenone, both of which present risks high enough to impact sow reproduction and performance. Grow-finish pigs are also affected by DON, which can impact gains, gut health and feed efficiency.

• Poultry

Overall, the samples showed a low to moderate mycotoxin risk for poultry, with the risk increasing the farther East the samples came from. Compared to swine, poultry are projected to have a lower risk from DON, but the risk presented by mycotoxins is still high enough to impact gains/feed efficiency and gut health.

• Ruminants

The 273 samples of corn with a high moisture content (HMC) included an average of 6.1 mycotoxins per sample, creating a distribution of 60% low-risk and 40% moderate- to high-risk samples. On average, there is a low risk for beef and cattle; while the presence of mycotoxins has the potential to affect performance, overall, this risk is very manageable. Producers in the East and upper Midwest are projected to have the highest risk due to dry conditions followed by heavy rainfall.

The data from 2020 suggests much more prevalent and higher levels of aflatoxin B1, which should be of particular interest to dairymen. Dairy producers should monitor and test for mycotoxins in corn silage, especially if their operations are located in high-risk areas. Additionally, aflatoxin B1 can convert to aflatoxin M1, which can be excreted in the milk, leading to food safety concerns.

Managing mycotoxins

There will always be mycotoxins in feed, but knowing what they are and what risk level they pose is critical to mycotoxin management. The Alltech 37+ mycotoxin analysis test provides a realistic picture of the mycotoxins in feed ingredients or TMRs. This comprehensive test allows for quick diagnosis, effective remediation and planning for future control measures. To learn more about having a 37+ test completed on your farm, please visit the Alltech 37+ mycotoxin page.

Dr. Hawkins recommends testing each time you change your feed or introduce a new feed ingredient in order to properly measure your mycotoxin risk. Going forward, risk levels can change based on fermentation, and we need to watch out for “storage mycotoxins.” There have been forecasts of a dry spring, but the mycotoxin risk is fluid and always changing.

To watch the complete 2020 U.S. Harvest Analysis, click here.

Have a question or comment?

An international research team at the University of Surrey in the United Kingdom has established a link between the outcome of COVID-19 cases and the regional selenium status of people in China. The data was based on the real-time numbers of confirmed cases, recovery rates and mortality rates in each province or city. When analyzing these populations, researchers observed an association between the population’s selenium status (based on hair samples) and the rates of recovery (Figure 1).

In the Hubei province, whose capital is Wuhan, it was found that Enshi City had recovery rates that were 36.4% higher than other cities within the region, where the overall recovery rate was 13.1%. Enshi City is known for its high selenium status. Outside of Hubei, in the Heilongjian province of north-eastern China, where the selenium status is notoriously low, a 2.4% increase in mortality rates was observed.

China is home to people with both the lowest and highest selenium statuses in the world. Geographical differences across the country result in varied soil compositions, which can alter selenium levels. It is these differences in soil selenium levels that influence how much of the trace mineral enters the food chain from livestock feed, meat, milk and eggs, and the end consumer. Therefore, human selenium intake is very much dependent on the environment in which the crops, plants and livestock are raised.

Figure 1: Correlation between COVID-19 recovery rate in 17 cities outside Hubei, China, on February 18, 2020, and city population selenium status (hair selenium concentration) analyzed using statistical methods (mean ± SD = 35.5 ± 11.1, R2 = 0.72, F test P < 0.0001) Copyright ^© Rayman et al., on behalf of the American Society for Nutrition, 2020.

Selenium and its role in immune defense

Selenium is an essential trace element for both humans and animals and is required in small amounts for normal health, growth, reproduction and immune defense. It also provides a source of antioxidants, which help to address diseases related to oxidative stress.

Previous studies have shown the antiviral effects of selenium and have linked the evolution and spread of viral infectious diseases, such as swine flu and bird flu, to areas where soil selenium levels are lower (Harthill, 2011). Other studies have observed more severe viral symptoms and infection rates when dietary selenium is low (Beck et al., 2001).

Viruses produce reactive oxygen species (ROS) as part of their biological makeup. These ROS are believed to be combated by glutathione peroxidase, an important antioxidant for cellular defense in which selenium plays a major role. As such, it is believed that several cellular and viral mechanisms involving selenium and selenium-containing proteins can influence the outcome of viral infections.

Selenium and functional food: What do these findings mean for human health?

It is important that we consume a well-balanced diet that incorporates adequate amounts of selenium to maintain our antioxidant capacity and immune defense. According to U.S. standards, the recommended dietary allowance (RDA) for selenium in humans is 55 micrograms a day.

Dietary sources of selenium include nuts, grains and vegetables, with Brazil nuts being the richest source of selenium. However, their content is highly variable and can range from 0.03 to 512 micrograms, the latter level being potentially harmful. In vegetables, up to 40% of selenium can be lost through cooking.

Highly bioavailable and organic forms of selenium have kick-started a new era in the availability of selenium-enriched products. Enriched meat, milk and eggs that contain up to 35 micrograms of selenium (more than 50% of the RDA) have been successfully developed and tested using SEL-PLEX^®, Alltech’s proprietary selenium-enriched yeast (Surai et al., 2009). Livestock that are supplemented with selenium-enriched yeast show improved health, disease resistance, fertility and antioxidant capacity. Due to the high bioavailability of organic selenium-enriched yeast, the trace mineral is effectively transferred to subsequent animal products. The result is meat, milk and eggs with consistently higher selenium levels that are available to us for consumption.

As we can see from this population study, organic selenium-enriched yeast could provide a promising development in functional food for human immunity and general health.

References are available upon request.

The rise of insulin prices over the last decade, plus the cost of pumps and syringes, has made treatment for diabetes more expensive than ever. Will a cost-effective insulin replacement ever exist? Dr. Ronan Power discusses Alltech Life Science's breakthrough in insulin pills for diabetes.

The following is an edited transcript of Tom Martin’s interview with Dr. Ronan Power. Click below to hear the full audio.

Tom:            Insulin prices have more than tripled in the last decade, and because insulin cannot be taken orally, pumps and syringes can add significantly to the cost. The result? This treatment is quickly becoming unaffordable for many diabetics, but insulin therapy is critical for most of them, and there's a search for options. One might have been found.

                     Dr. Ronan Power, vice president of Alltech's Life Sciences division, joins us to talk about something of a revolution in the treatment of diabetes. Thanks for joining us, Dr. Power.

Ronan:          Thank you, Tom.

Tom:            Tell us why, first of all, there is this need. I kind of described it in the introduction, but diabetes is a huge problem in this country, I assume.

Ronan:          Absolutely. It's a huge problem not only in the Western world, but it's becoming more and more of a problem in countries that have, if you like, found affluence in the last two to three decades and are adopting more and more of a Western-style diet and lifestyle. It's becoming a really, really big problem. I think one of the figures I saw most recently was an estimated 360 million sufferers worldwide, but that's only diagnosed cases.

                     Of the subtypes of diabetes, the two main ones, of course, people will be familiar with are Type 1 and Type 2. Type 1 typically hits younger people, and that is a type of diabetes where the cells in the pancreas that produce insulin are destroyed, and that can be an autoimmune-type disease or a reaction to a virus, in some cases. The most prevalent form is Type 2, which used to be called “adult-onset diabetes,” but now, it's creeping downwards in the age group and it's hitting people as young as four years of age — even younger — and that's part of the associated obesity epidemic or pandemic that we see in the world today.

Tom:            We're seeing studies that are projecting that if these rates, these obesity rates, continue at current trends, more than half the population of almost 40 states in the United States will be obese in 2030. What are the implications of failing to stop and reverse that trend?

Ronan:          I think they're absolutely massive — and I would say 50% is a conservative estimate. If you look at the implications of obesity as they relate to diseases like diabetes, there is a condition known as metabolic syndrome that precedes the development of diabetes. This is a condition which is characterized by not just obesity, but high blood pressure, high cholesterol or dyslipidemia. That's abnormal blood profiles, high triglycerides and so on and so forth. That can predispose people to many, many diseases, particularly coronary vascular disease or cardiovascular disease and pulmonary disease. That's even before you hit any diabetes threshold. Once people develop diabetes, there's a whole range of attendant problems that come with that, as people are aware of, but one of the larger problems, in my opinion, is the state of insulin resistance that begins to develop in people who tend to be overweight or have a higher-than-normal body mass.

                     Insulin resistance in itself can cause huge problems. Let me just mention an example. One of them is called PCOS, or polycystic ovary or ovarian syndrome. That's becoming a huge problem in the female population in terms of reduced fertility, inability to conceive and inability to sustain a pregnancy. That's a direct implication of insulin resistance. So, we're not just talking diabetes here; we're talking much broader, more debilitating conditions of life, if you will.

Tom:            We're here to talk about something that you're working on, which is an alternative to insulin that you have in development now. Can you tell us about this?

Ronan:          Sure. This is, I guess, the culmination of about 12 years of work in our labs here at Alltech. This started off as a plant-based or a botanical-based compound we found which was able to increase energy production in cells, or seemingly increase energy production in cells. Actually, it turned out to be that it improved energy consumption. So we've been studying this for quite some time, and we actually have made a lot of variance of this particular compound. We isolated it. We synthesized it. We made variations on a theme, as it were. Today, we have a compound, which we call Compound 43 — obviously a very imaginative name, the number 43, the variation of the compound which we developed. So, Compound 43 has got a very unique ability in being able to bind to insulin receptors and activate that receptor in the absence of insulin.

                     In effect, if you want to view the action of insulin on a cell as a lock and key mechanism, imagine that insulin is the key. It fits into a lock, which we shall call the insulin receptor. When both lock and key are working correctly and the mechanism is turned appropriately, that opens a glucose channel and allows glucose to enter the cell and be used properly.

Tom:            Let me make sure I understand up to this point. The compound that you're working on replaces that key.

Ronan:          It replaces the key. It can activate the lock even when the lock is broken, because in Type 1 diabetes, you're missing the key. In Type 2, there's something wrong with the lock mechanism; it doesn't work properly, or not at all, in some cases. But what this compound does is it binds to the insulin receptor (i.e., the lock) and can open it.

Tom:            So, it's doing the work of the insulin.

Ronan:          It's doing the work of the insulin. What we have, in effect, is an insulin replacement. It doesn't bind to the insulin receptor in the same place as insulin. It binds at different locations. Its purpose, simply, or what it does, is it brings the two arms of the insulin receptor together, and once they join together, it activates the insulin cascade inside the cell, which then allows that glucose door to open and allow glucose in.

Now, it's not a runaway reaction, by any means. It does stop, so there is a finite half-life of this compound, which we've determined to be about eight to ten hours. It doesn't crash the blood glucose. It takes it down, but it doesn't bottom it out at a dangerous level.

Tom:            Now, as I understand it, this would be administered orally as opposed to a shot.

Ronan:          Absolutely. This is our big breakthrough in the last year. When we initially tested this compound, we were using it in the traditional insulin-type way, of a subcutaneous injection, or even an IP, an intraperitoneal injection, but we've now developed a formulation which can be taken orally in tablet form, pill form, which works very well indeed. We have actually tested that in mouse models of diabetes, several different mouse models of diabetes, and it works perfectly well. The compound itself, we've also tested in human cell lines — liver, skeletal muscle, all of the major organs that are impacted by diabetes — and find that it works beautifully.

                     It can even be used in concert with insulin, in some cases, because when I describe the Type 1 and Type 2 diabetes, especially for Type 2, there are various levels of it. For some people, insulin works, but not as well as it does in the normal case. That's what we term “insulin resistance.” Insulin resistance can be a graded or a gradated type of resistance. That's why some diabetics, Type 2 diabetics, still take insulin, but this can actually help insulin action, so it works in concert with insulin, in some cases. Because it doesn't share the same binding site, it can be an additive or synergistic effect.

Tom:            I'm sure that anybody who is suffering from diabetes and hears this is going to be quite excited and quite hopeful.

Ronan:          Yes.

Tom:            How should they temper that hope? How far off are you, do you believe, from going to market with this?

Ronan:          First of all, I wouldn't be sitting here if I didn't believe this was a breakthrough. I believe that we can get this out through what we call a phase-one clinical trial in humans within about three years. If it shows promise there, we hope to go right ahead and follow with phase two or three. Best-case scenario, Tom: we're probably looking at six years to market, but I think that's a fast track. That will be a fast track, but I'm hopeful that when we approach FDA with this, they may, in fact, look upon it and say, “Okay.” This type of compound is not unknown, so it has a pretty good historical safety profile.

I believe that there is an urgent need to come up with alternatives to insulin. For whatever reason, Tom, there is some egregious price gouging going on in that market, and people are dying as a result, and I'm not being overdramatic in saying that. You can look at the press, the news, a whole variety of states, and see that people are actually rationing their insulin, using less-effective forms. People have to decide between groceries and insulin, and in some cases, it costs people more than their monthly mortgage, so it's a desperate situation for something that was sold — the patent for this — a lot of people aren't aware that the patent for insulin was sold in 1923 to the University of Toronto for the princely sum of CAN$3.

Tom:            And I understand, now, that a vial of insulin can be manufactured for about $7.

Ronan:          Yes, it is, depending on the grade and the type. It can vary from a very low price like that up to — I'm not sure of the final cost, but certainly, I would guess, no more than $20 or $30, but it's selling for people without insurance — I hear horror stories of people paying $400 to $500 a vial for the material, and that's something that, when you open it, you have to refrigerate it, and it's active for 28 days. What we're looking at is a tablet or a pill, and it's stable for two to three years.

Tom:            I believe I heard you say that a dose, let's put it that way, would last eight hours or so.

Ronan:          Yes.

Tom:                          So, theoretically, a person could take two of these pills a day.

Ronan:                       Theoretically, yes. Yes. It will vary per individual. And obviously, that would have to be determined medically by a person's physician, but I would think that, under normal circumstances, two pills per day, based on our studies, our modeling so far.

Tom:                          When you think beyond FDA approval and marketing and use, Ronan, what do you see out there as the implications for how this impacts the quality of life of diabetes patients?

Ronan:                       Well, if you look upon it this way, you'll see people in public and in restaurants looking at their little glucose pumps. You know, people still, every morning, come along and take that pinprick on their finger and look at the glucose strip and so forth. So, there’s a whole lifestyle associated with living with diabetes. Probably the biggest drawback I see for people is, you know, having to use all of the paraphernalia — the syringes, the needles, the phobia about the needle itself, even though, nowadays, it's tiny. Very thin needle indeed. But there’s so much that goes along with using insulin. I mean, having to refrigerate it, which is no problem in the West, but think about countries where refrigeration is not an option. Think about Africa.

Tom:                          Oh, it can limit your mobility too.

Ronan:                       Of course. Of course it can. And you know, we've done our stability testing on this. I mean, some of the models we use are mice. And can you imagine — we can put this compound into a mouse diet, right? Into a laboratory mouse diet, and retrieve it, fully active, 1 year later. We can pull it back out. So, it's an extremely stable compound.

                                    Now, insulin is basically a protein, so it will degrade. And that's why you have to refrigerate it, and it loses potency after a very limited period indeed. I think 28 days is the expiration on it. So, there are huge benefits for something like this, and indeed, companies have been struggling to develop an oral insulin preparation for decades, but I don't think anybody has ever looked at an alternative to actually physically activating the receptor.

Tom:                          Since this compound is being designed to treat a disease, I assume it would have to be approved and marketed as a pharmaceutical.

Ronan:                       Oh, absolutely, yes.

Tom:                          And that has implications for the company.

Ronan:                       Uh-huh. Yes.

Tom:                          Tell us about the discussions around that topic, because I know it's a very complicated one.

Ronan:                       Oh, it is. It's certainly a departure for Alltech. We have always been — well, apart from our beverage division and crop science — we've been very much associated with animal feed supplements and health supplements for animals. So, our dealings with regulatory bodies have been with the European Food Safety Authority in Europe (and) the Center for Veterinary Medicine branch of the FDA here, which deals with all of the ag products, if you will. We've had little or no dealings with the FDA itself, even though we did have initial discussions with them concerning a supplement we have called AT-001 some years back. But I think that while it will be a departure, it's an exciting new horizon for the company to actually get into something. We launched Alltech Life Sciences for that very purpose probably 8 or 9 years ago, to try to transfer some of our technology and products from the animal health arena to the human health area.

Tom:                          And it does seem to complement an announcement made at (ONE: The Alltech Ideas Conference) about the establishment of an Alltech foundation in partnership with UK Healthcare, which, of course, is human-oriented.

Ronan:                       Yes. Yes. I think that's an exciting prospect also. There are many, many excellent researchers and research laboratories at (the University of Kentucky), as you know. And many of those are active in the diabetes area, and I look forward very much to perhaps collaborating with them in the future. This may just be the first of many such preparations that we develop.

                                    We have other products in the pipeline, some of them related to diabetes. And as you know, we're also interested in neurodegenerative diseases. And we're also interested very much in intestinal health for humans. And by that, I mean, you know, trying to prevent this condition that is becoming quite pervasive in the U.S. and, indeed, in the West, which is sparked by what's called — I guess, rather unsavorily —  leaky gut syndrome. So, that leads, in turn, to a nonalcoholic fatty liver disease, and that's a condition that afflicts perhaps 20% of the adult population in the U.S., to varying degrees. So, that’s the third area: digestive health. So, neurodegenerative health, digestive health and, also, the diabetic care or, if you like, metabolic health. That will be our three areas of focus.

Tom:                          Well, I know that you’re a consummate professional, but I also have to believe that, on a personal level, that this accomplishment feels like a pretty good achievement for you.

Ronan:                       It has been a long road. I have been very, very fortunate, Tom, in having some excellent colleagues working with me, many of whom have what I call “green fingers” in the laboratory — excellent scientists. Dr. ZJ Lan is one. I have two very good ladies working in the lab, Katie Eastridge and Hayley Kincaid. I’ve got Dr. Rijin Xiao, who works on the bioinformatics side of things, all the data collation. And Ryan Goettl is a young man who’s also working on bioinformatics. We’re all held in check and held together by Ms. Jeannie Francis, who herds us wherever we need to go, but I’ve been very fortunate, and our outside collaborations have also been excellent. It’s 12 years. It seems like a long road, but it has gone in a flash. So, it has —

Tom:                          As these things have a way of doing.

Ronan:                       Indeed.

Tom:                          Well, Ronan, good luck with this. Congratulations as well. And we will be anxious to follow your progress.

Ronan:                       I look forward to updating you as we go along, Tom. Thank you very much.

Tom:                          Dr. Ronan Power, vice president of Alltech’s Life Sciences division, we thank you very much.

Dr. Ronan Power spoke at ONE: The Alltech Ideas Conference (ONE). Click here to learn about ONE and how you can access innovation on demand.

EINVU project sees Alltech collaborate with leading institute for applied research, Nofima

[BERGEN, Norway] – Developing more robust and sustainable salmon through nutritional product innovations and associated scientific documentation is the aim of Alltech’s latest aquaculture collaboration. Global nutrition company, Alltech has teamed up with leading fisheries, and the institute for applied research, Nofima, on six research licences for salmon farms Blom Fiskeoppdrett, SalmoNor and Salten FoU. As part of this series of large-scale experiments; industrial production, organic minerals and heterotrophic microalgae will be tested.

The project has been named EINVU, a Norwegian acronym that stands for “Nutritional Innovations” — the key to solving major welfare challenges. Over the next three years, trials will be conducted on each farm responsible for operating the licenses. Alltech will supply products for testing, as well as overseeing the management of the projects. Nofima will be responsible for trial design, analysis, interpretation of data and reporting.

“In the project, we want to investigate whether we can achieve positive performance results, similar to what we have seen in small scale trials. It will be very exciting because that’s where fish really get challenged,” said Elin Kvamme, project manager at Alltech.

Farms have been chosen to represent three different parts of Norway, all with different operational challenges. During the trial period, the effect of various levels of organic trace minerals and microalgae will be sampled and tested to monitor progress. From small-scale to commercial production, many factors like operational management and environmental conditions can cause stress for salmon. For example, if temperature fluctuations, oxygen and sea lice infestation occur concurrently, the salmon can become weak, leading to disease and, in some cases, increased mortality.

“In small scale experiments with organic minerals, we see that the mineral deposit in the fish is higher and the fish can better withstand stress,” explained Ms. Kvamme. “Growth is also better; we see a lower mortality rate and reduced gaping. When it comes to the use of microalgae in the feed, we have seen increased growth, better pigmentation and improved EPA + DHA levels.

“The future supply of fish oil is uncertain, and alternatives must be sourced. Heterotrophic microalgae have high levels of omega-3, and it is, therefore, appropriate to study the effects of replacing marine raw materials with this sustainable source.”

In 2012, Alltech entered into a strategic collaboration with Nofima to document the effects Alltech products and solutions have on salmon. “We are very pleased that Nofima, a respected research organisation, has partnered with us on this journey. All products have been carefully tested and published in reputable journals,” added Mr. Kvamme.

For more information click here.

There are an estimated 450 million people living with diabetes worldwide according to the International Diabetes Federation (IDF), with a staggering 53% increase expected by 2045. In a breakthrough that may offer hope to those affected by the chronic disease, researchers with Alltech Life Sciences have developed a possible alternative to current insulin treatments. The compound, called NPC43, is effective when administered either orally or by injection.

The results from 12 years of scientific research were recently published in the peer-reviewed journal Cellular and Molecular Life Sciences. The paper details the development of the novel treatment for both Type 1 and Type 2 diabetes. NPC43 works by reactivating dormant insulin receptors, thereby allowing blood glucose to enter cells. Furthermore, it inhibits glucose production from diabetic liver — a condition associated with insulin resistance that worsens the problem of having excess glucose in the bloodstream.

“Imagine insulin to be a key and an insulin receptor to be a lock that allows glucose to enter cells,” explained Dr. Ronan Power, chief scientific officer at Alltech. “Type 1 diabetics can’t produce keys and, although Type 2 diabetics can, they possess broken locks. The result of either type is that the glucose door remains shut. What we have discovered is a way to open the lock without a key, even if the lock is broken.”

In addition to enduring the pain and anxiety of injections, those living with diabetes are often faced with limited access to affordable treatment. Insulin prices have more than tripled in the last 10 years, becoming unattainable for most underinsured patients.

“The compound has the potential to be revolutionary,” said Dr. Zi-Jian Lan, senior research scientist with Alltech Life Sciences. “Since it works when administered orally, this could mean the elimination of injections, pens and pumps, and provide an affordable alternative to insulin.”

The implications for NPC43 could extend beyond diabetes to any syndrome or disease associated with insulin resistance. That may include polycystic ovary syndrome (PCOS), cardiovascular disease, obesity and non-alcoholic fatty liver disease.  

The research was conducted in cultured human cells and in animal models of severe Type 2 diabetes. The next milestone in the development of NPC43 will be clinical trials.

Alltech, Inc. has filed an international patent application covering this technology (PCT/US18/30371).

Download image: https://photos.alltech.com/pf.tlx/sVsSMsWfaWo

Caption: In a breakthrough that may offer hope to the millions of people affected by diabetes, Dr. Zi-Jian Lan and his research team with Alltech Life Sciences have developed a possible alternative to current insulin treatments.

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press@alltech.com

Tests of varying scientific nature and credibility are widely alleged to have the ability to differentiate between good and bad organic trace minerals (OTMs). The basic parameters that can be analyzed include mineral percentage, nitrogen-to-mineral ratio, percent of bound mineral, molecular weight, bioavailability and stability. While some of these analyses can provide meaningful and valuable information about defined or individual products, understanding the limitations of these tests is critical if they are to be successfully applied in the assessment of OTMs.

Mineral percentage

Accurate quantification of the total mineral content of OTMs is routinely used by all manufacturers, and cost comparisons between OTMs will consider this when calculating their relative value. Total mineral content, however, gives no information regarding OTM bioavailability and, as such, is limited in terms of calculating the true relative value of a product.

Nitrogen-to-metal ratio

Calculating the molar ratio of nitrogen to metal can be a useful way to assess glycine-based chelates. When assessing more complex products, such as proteinates, the nitrogen-to-mineral ratio will not give an accurate reflection of the true potential for mineral bonding. More complex amino acids can bind metal atoms through their side chains via sulfur and oxygen atoms. As there is no involvement of nitrogen in this side chain bonding, it is possible to underestimate the potential for binding by only considering the nitrogen-to mineral ratio. The nitrogen content of various products can also be artificially inflated, giving the false impression of a product with high nitrogen-to-mineral ratio.

Solubility

It is often asserted that an OTM must be soluble to be bioavailable, but many peer-reviewed publications have shown that insoluble OTMs have the potential to be more bioavailable than their soluble counterparts. An evaluation of OTM solubility will be of little benefit unless one considers the effects of the digestive processes and the changing pH environment within the GI tract.

Molecular weight

Numerous claims have been made about comparing OTMs based on size, and these claims erroneously indicate that a smaller-sized bonding group creates a more stable and more bioavailable OTM. Correlating the molecular weight of an OTM with its stability constant indicates quite clearly that, rather than size being of critical importance in generating a stable OTM, the type of bonding group is of far greater significance.  

Bioavailability

In vitro lab-based assays, which attempt to assess bioavailability, have been developed, making use of cell culture-based assay systems that can determine the transfer and uptake of minerals across cellular membranes. These techniques, however, can’t accurately reflect the influence of digestion on the OTM. As such, their value when comparing different products is limited.

Stability

When we talk about the stability of OTMs, we are referring to the bond strength that exists between the bonding group and the mineral; the greater the bond strength, the more stable the product. Polarography can be used to assess the bond strength of OTMs — but polarography is only suitable to test materials in solution and can only assess the soluble fraction of organic mineral products. OTMs are increasingly solubilised as a result of the in vivo conditions of the GI tract, so the results of the polarographic tests alone should be interpreted with caution.

Percent of bound mineral

Historically, determining the percent of bound mineral required utilizing filtration through a low-molecular-weight membrane. The mineral retained behind the filter was assumed to be bound, while the mineral in the filtrate (solution) was assumed to be unbound. Such methods, however, are subject to manipulation, as changing the pH of the buffer can cause precipitation and lead to false estimates of the true bound mineral percentage.

The only validated assays that fully quantitate the bound mineral level of an OTM utilize techniques known as ATR-FTIR (attenuated total reflectance Fourier transform infrared) and PXRD (power X-ray diffraction) and were developed by researchers at Alltech’s European Bioscience Centre.

The first assay uses a form of infrared (IR) spectroscopy to measure the bound mineral percentage, whereas the second assay uses a form of crystallography to measure the unbound mineral level. These two assays are complementary to each other, and both are peer-reviewed and published. In the case of the IR assay, this was independently validated and verified by the Central Reference Laboratory (CRL), which reports directly to the European Food Safety Authority (EFSA).

Conclusion

While simple tests based on mineral percentage, nitrogen-to-mineral ratio, molecular weight, bioavailability and stability are used by different manufacturers, these tests only provide limited information about individual products and are not suitable for comparing different classes of product. If products will continue to be compared through these tests, understanding their limitations is critical.

The only validated assays to assess mineral chelation are based on the use of techniques known as ATR-FTIR and PXRD and were developed and validated by researchers at Alltech’s European Bioscience Centre. 

Click here for more information on Alltech's Mineral Management program. 

References:

Byrne, L. A., Hynes, M.J., Connolly, C.D. and Murphy, R.A. (2011) 

Analytical determination of apparent stability constants using a copper ion selective electrode. Journal of Inorganic Biochemistry, 105(12):1656-1661.

Byrne, L.A. (2010) Analytical assessment of peptide-metal interactions and subsequent stability. Ph.D. Thesis. Dept. of Biology, National University of Ireland, Maynooth, Ireland.

Cantwell C, Byrne L, Connolly C, Hynes MJ, McArdle P, Murphy RA. (2017)

Quantitative assessment of copper proteinates used as animal feed additives using ATR-FTIR spectroscopy and powder X-ray diffraction (PXRD) analysis. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2017 Aug;34(8):1344-1352.

Murphy R.A. (2018) Organic Trace Minerals: Optimised Stability Enhances Bioavailability International Animal Health Journal Vol 5 (2) 28-32

Murphy, R.A. (2018) Minerals, Meals and Molecular Malnutrition: How Mineral Form Can Impact Feed Quality and Cellular Health. International Animal Health Journal Vol 5 (1) 42-46

Murphy R.A. (2015) OTM bond strength, relative stability

Feedstuffs July

Murphy, R.A. (2010) Drilling into mineral analysis – structure and stability explained. All about feed Vol 1 (4) 21-23

Murphy, R., (2009).  Chelates: Clarity in the confusion. Feed international January/February 22-24.

The following is an edited transcript of Tom Martin's interview with Dr. Karl Dawson, co-director of Alltech’s Center for Animal Nutrigenomics and Applied Animal Nutrition. Click below to hear the full interview:

Tom:            Over the last 10 years, scientists at Alltech have been using nutrigenomics to develop new feeding strategies and, ultimately, redefine animal nutrition. What are the practical applications of this science, and what does it mean for the future of aquaculture specifically? Joining us to explore these questions and more is Dr. Karl Dawson, vice president and chief scientific officer at Alltech. Thanks for being with us, Dr. Dawson.

Karl:             It's a pleasure, Tom.

Tom:            Let's begin with a fundamental question: What is nutrigenomics, and why is it such a valuable tool?

Karl:             Well, nutrigenomics is really one of the new tools or sciences that we can use to evaluate what specific nutrients or the nutrition of an animal, or a human, is doing to the process of gene expression. Today, we're looking at many different tools that are from this molecular-based science. We can use nutrigenomics, which looks at the transcription or expression of genes, and there are other things, for example, like metabolomics, which looks at the ability of a nutrient to influence the metabolites that are developed in the bloodstream. These are different tools that we're using today that give us a much deeper view of what nutrition does in an animal's body.

Tom:            In a recent panel discussion, Farming the Future, you said that nutrigenomics is really going to redefine things, if it hasn't already. Can you elaborate on that?

Karl:             Yes. We are using nutrigenomics to find new concepts and challenge the nutritional concepts that are out there today. We are just answering such questions as “What does an antioxidant do, what does it do in the animal's body and to improve animal health?” We can find substitutes for the traditional antioxidants that are out there.

                    We've done other things, for example, like defining trace mineral requirements in animals. We've used nutrigenomics to redefine what we thought was the expected or needed levels of minerals in an animal's diet. Many of these things are changing what we think about in terms of the way a nutrient will interact with the animal, providing for their health and well-being.

Tom:            The name of the field, “nutrigenomics,” might lead someone to believe that it's limited to exploring how nutrition influences the expression of individual genes. But it's more than that, isn't it?

Karl:             Yes. Well, nutrigenomics is really built around the nutrition concept — that's the nutrient or nutrigenomics part of it. The term that's probably more appropriate is the term “transcriptomics,” which is measuring gene expression overall. We can look at such things as the effects of a disease process on gene expression, or how a change in environmental temperature affects gene expression. All of these factors influence gene expression; nutrigenomics is just focusing on what the nutrients in the animals’ diets are doing.

Tom:            Okay. Let's turn our nutrigenomics focus over to aquaculture. How is this tool being used to define new feeding strategies for fish?

Karl:             Well, we have lots of examples of things that we're doing today. Nutrigenomics — or this gene expression measurement — is something that is fairly new in fish, but it is becoming a very popular tool. In the last seven or eight years, there's been a surge of scientific interest in looking at gene expression and what influences gene expression. We've been particularly interested in looking at such things as “How does nutrition influence fillet quality from a fish?” We can identify the specific gene markers that are correlated with such things as the firmness of a fish fillet. Those things are highly correlated. Now, that's very interesting because that's not something we've been able to do in the past — to go in and find specific markers. That doesn't mean the fish does not have those genes. It means it does not have the ability necessarily to express those genes. So, it's not just genetics here. We're talking about the way genes are turned on and turned off.

                    We've used this very specifically in recent months, or in the last two years, to look at some very specific feed additives that we might use in salmon diets. One of the big problems for the salmon industry today is the problem with sea lice. We've come up with ways to influence the infestation of fish with these sea lice by changing what those fish are receiving. We did that by taking specific feed materials that we had identified and had some history with, and we looked at how they influence gene expression. We tried to find feed materials that would enhance things such as mucin production on the surface of the fish and the innate immunity of the fish. That gave us a lot of clues before we had to do any real animal experimentation to find materials that were very effective.

Tom:            Are these salmon now better able to resist sea lice?

Karl:             That's the point we've made in the last six months or so. We do have some fish that, while they will still be infested, the infestation rate tends to be much lower. So, if we look at the number of fish that have fewer than 20 lice, for example, we'll see that we can change that distribution and find a lot more fish that have fewer lice. It's not a total resistance to infestation, but it changes the ability of the fish to support this parasite.

Tom:            How long does it take for a sample from the herd, the flock or the school, in this case, to yield useful data?

Karl:             This is usually a fairly quick thing. Typically, we look for gene expression changes within a matter of days. It can be within a matter of hours. One of the most interesting studies we reviewed just recently was one where we looked at how the sea lice themselves influence the gene expression in the fish. It's very interesting to see, but within three days, those sea lice would change the immunity of those fish, and it’s not by increasing it — they tend to depress it.

                    They also depress such things as the ability of the fish to respond to wounds and wound-healing mechanisms. This is a very unique observation because we're actually saying that this lice — or this louse — is changing the ability of that fish to recover and is influencing the fish gene expression just by attaching to the fish.  

Tom:            What are some specific ways aquaculture producers can use the information that you're gleaning from this nutrigenomics research?

Karl:             Well, we know quite a bit about specific nutrients today. For example, mineral supplementation is one that we have worked with quite a bit. We do know that if you provide selenium in a very rich organic form such as selenium yeast, you can change the genes, or the expression of genes, that result in immunity and such things as mucin production on the surface of fish.

                    Those are things that are real, that are being used today, but probably not attributed directly to nutrigenomics. We don't go out and measure the gene response. But, as a result of what we know from gene expression, we can predict what's going to happen in the animal. We can do that quickly, too, because our turnaround time on understanding gene responses is a matter of days instead of waiting for a full production cycle.

Tom:            So, it's fair to say that this science is really bringing a new level of precision.

Karl:             Right, absolutely.

Tom:            What are some new commercially useful feeding concepts that have come directly from the use of this molecular tool?

Karl:             Well, as I indicated, minerals are one that is very much being used today — sources and types of minerals that are being used and actual levels of minerals. Mineral supplementation is a common one. We're doing quite a bit of research right now using yeast cell wall components to address what's happening within the fish in terms of disease resistance and, most recently, in terms of nutrient absorption. It appears these materials are also influencing the tight junction proteins that make up the intestinal tract and change the way the fish absorbs its nutrients.

                    Those are real things that are happening today that will change how we think about providing nutrition to fish.

Tom:            Can this tool be used to quickly determine the value of newly developed feed supplements, and how?

Karl:             Yes. That's really the approach we use right now. One of the interesting models that we're using today is nutrient injection. If we want to test out a new product or nutrient, we can inject the fish with small amounts of that material and evaluate what's happening with gene expression.

                    As we do this more and more, we're building a pattern, or an encyclopedia, of responses that we would like to see. We've already done that to some extent with some of our yeast products and some of our minerals. So, we're starting to understand what those responses have to be to speed up the time it takes to evaluate new nutrient concepts.

Tom:            How will the tool be used to demonstrate the effects of maternal nutrition on the growth, development and disease resistance of offspring?

Karl:             That's getting into another term, “epigenetics,” the concept of being able to pass on traits that aren't really related to the actual genetic material. We don't have a lot of experience in fish. Although we know that a healthier mother tends to have healthier offspring in fish, we've never been able to measure that directly. However, in some of the other livestock species we're working with, it is a very important tool.

                    One of the observations we've made in pigs, for example, is that by feeding a mother a very specific prebiotic late in pregnancy, we can completely change the gene expression in a young piglet, even at weaning. This is after the pig is quite developed. You're working with a new piglet that has a completely different nutritional set of requirements — it is something totally different.

                    It is something that we're using a lot more in livestock species than aquaculture species, although we have some ideas in the next couple of years that we're going to try out and see how we can make that work in fish.

Tom:            Dr. Karl Dawson directs activities at Alltech’s bioscience centers around the world, including the Alltech Center for Animal Nutrigenomics and Applied Animal Nutrition, where he is the co-director. Thank you for being with us.

Karl:             Thank you.

Dr. Karl Dawson spoke at ONE: The Alltech Ideas Conference. Click below to view presentations from ONE18:

The following is an edited transcript of Tom Martin's interview with Dr. Gregory Jicha, chief clinician and professor at the University of Kentucky Alzheimer's Disease Center. Click below to hear the full interview:

Tom:              According to the Alzheimer's Association, an estimated 47 million people are living with dementia worldwide, and this number will triple by 2050. With a new case diagnosed every three seconds, can we stop the clock on dementia? It’s one of many questions we have for Dr. Gregory Jicha, chief clinician and professor at the University of Kentucky Alzheimer's Disease Center. Thank you for joining us, Dr. Jicha.

Gregory:         Thank you for having me.

Tom:              Given what you know from your research, are you optimistic that we can indeed stop the clock on dementia?

Gregory:         I am an incredibly optimistic person, but my thoughts are based in reality, and, yes, indeed, they are optimistic. We have discovered what causes Alzheimer's disease at almost every level. We have almost every piece solved, and we know how to go about attacking each of those targets with a set national plan in the U.S. of having a cure or medicine for the prevention of Alzheimer's by 2025. That means the medicines we hold in our hands today are the cures of tomorrow.

Tom:              You and your team are actively engaged in several state-of-the-art clinical trials in an effort to find better treatments and investigate potential cures for Alzheimer's disease and other forms of dementia. Can you tell us what you're looking into?

Gregory:         We're looking into a variety of different mechanisms, and what we know about Alzheimer's is it is a long process that begins about 20 years before the first complaints of memory loss. There is a slow buildup of amyloid in the brain, inflammation and oxidative damage, eventually leading to neurofibrillary tangles, cell death and dementia. So, we are looking at a variety of agents that may prevent the disease initially, and that once it's begun, may abort it at many of the different time points along that pathologic spectrum. The excitement is quite high. We do think that our best opportunities, the most promising medications that we're using currently, are in early prevention or in aborting the process very early on.

Tom:              Some time ago, Alltech and the University of Kentucky Sanders-Brown Center on Aging began partnering on research into the properties of the selenium-based Alltech product AT-001. A 2009 study using a mouse model found that the supplement significantly reduced the levels of amyloid plaques associated with Alzheimer's. The U.S. Food and Drug Administration approved the Phase I trial. That study confirmed that the AT-001 seemed to be preventing these plaques from migrating from the spinal fluid to the brain. You now have a Phase II trial underway focusing on volunteers who are at risk for Alzheimer's. Can you bring us up to date on the study?

Gregory:         That's correct. We've had a long-standing relationship with Alltech in moving AT-001 forward from the early animal preclinical studies, which not only have shown an impact on reducing amyloid plaques, suggesting a role in the early prevention and/or treatment of Alzheimer's, but even later stage changes like neurofibrillary tangles.

The Phase I study that we performed was really looking primarily at safety: How high could we push the dose of AT-001 safely in humans? We found no ceiling on that. We went up to 800 milligrams a day — that's 400 micrograms of selenium — and that is much higher than the U.S. RDA (recommended dietary allowance) for selenium. But in this particular form — the form produced by Alltech in the compound AT-001 — safety was not an issue at any dose. We were able to show in that study that we could use the high dose successfully over 12 weeks, and in that 12-week period, we saw tremendous changes in the research participants.

We saw an overall reduction in systemic inflammation — that's inflammation throughout the body — and we also saw very positive trends for reduction of Alzheimer's proteins in the spinal fluid. We've carried that forward now in conjunction with Alltech in a Phase II study. We have a large number of subjects receiving the supplement. Many folks have finished a one-year duration of high-dose treatment with AT-001.

Again, we're not seeing any signals suggestive of any safety concerns whatsoever. I am “blinded,” of course, during the course of the study, so I can't comment on outcome measures as of yet, but I will tell you the last subject out of that study will be December 2018. We hope to have data available by late winter or early spring 2019, which will hopefully confirm everything that we saw in the Phase I study and pave the way not only for AT-001 to make its mark as a supplement for brain health and the potential prevention of Alzheimer-like changes in the brain, but also as the scientists at Alltech move forward, trying to identify the active compounds to purify, to improve the efficacy, the ability of this supplement to promote brain health. I think we have a long road ahead of us with lots of discovery, and it's a very exciting time for us at the University in this partnership with Alltech.

Tom:              We would very much like to follow you on that. When the second phase is over, perhaps we can revisit and see where you are at that point.

Gregory:         Absolutely.

Tom:              Alltech founder Dr. Pearse Lyons was a major proponent of these studies. What do you recall about Dr. Lyons' enthusiasm and support?

Gregory:         Well, Dr. Lyons had inexhaustible energy, in my opinion. I never saw him moving at less than 180 miles an hour — that’s in brain thought processes, not in the rate at which he operated his car. Dr. Lyons was incredibly excited about the potential of AT-001 to impact humans. It's a supplement that's been used in the animal husbandry business for many, many years, and Alltech scientists have noted profound benefits on brain health in those animals. As the first endeavor to move Alltech discoveries directly into human care and disease prevention, this was something that Dr. Lyons really championed and maintained his enthusiasm for throughout the entire project.

Tom:              On another subject, you've noted that what we eat today can affect our cognition in the future. There is recent research that demonstrates that people who follow a Mediterranean-style diet enjoy a high level of protection against age-related cognitive decline. What components of this diet contribute to these benefits?

Gregory:         That is the million-dollar question when it comes to diet in humans. We know that composite diets like the Mediterranean diet, and the modified version that's become quite popular — the MIND diet — are certainly associated with better brain health outcomes. Unfortunately, we're currently lacking data on which of the components are most beneficial in that regard. Is it a potential combination of components where we need certain ingredients or certain food types to promote brain health, and the others are simply things that are carried along? I think that looking at the individual nutrients — much the way that we're doing with studies of AT-001, studies of omega-3 fatty acids and of other nutritional compounds —is someday going to unlock that mystery. We may find the ideal diet, where each of the components is based on science rather than our current coarse understanding of dietary needs for brain health.

Tom:              What additional lifestyle changes, cognitive exercises or dietary supplements might be of further use in preserving brain health and cognitive ability as we age?

Gregory:         I think that there are several areas of our lifestyles that do need to be modified for brain health, the first of which is cognitive exercise. I hear frequently from folks as they age that they can't wait to retire and do absolutely nothing. That may be great for relaxation, but that is the worst thing in the world for your brain. We know that if you don't use it, you will lose it.

                        Recently, the National Academy of Sciences had an advisory panel looking at brain health and prevention, and their number one recommendation was cognitive activity. That was followed by management of medical issues such as blood pressure control throughout middle age and later years.

                       We know that negative impacts on the body are also reflected through negative impacts on the brain. If you're not seeing a doctor and have those medical problems, get out there and get those problems addressed.

                      The third is physical activity. We're not talking about devoting your entire life to becoming a gymnast or a heavyweight champion; what we're really talking about here is a simple 30 minutes, three days a week, of high-intensity exercise. It reduces your risk for a disease like Alzheimer's to almost one-third. That's a 300 percent improvement in your brain health through that single activity.

                      What we don’t yet understand is the impact of combining all those things. Perhaps if each one lowers it by a third, and we're looking at a third of a third of a third, we may be to a point where there is a 90 percent plus chance of eliminating the future threat of Alzheimer's for an individual person who's maintaining that healthy lifestyle.

Tom:              Are there any emerging technologies or innovations that excite you that you're keeping your eye on?

Gregory:         There are a number of exciting technological innovations. Many of these are in the area of genetics. Genetics have helped us unlock the mysteries of Alzheimer's disease, and more importantly, they're helping us unlock the secrets to brain health and the individual cellular pathways that are important for us to target through interventions, nutritional supplements and medications.

                      One always thinks about genetic discoveries as being something that we're simply left with — that you're “stuck” with genes and if you have that risk, there is nothing you can do about it. But I think what we've learned from precision medicine in cancer is that understanding your genetic risks can help us to develop a personalized prevention program for Alzheimer's disease — a personalized program for your individual brain health.

Tom:              Dr. Jicha, what would you say you enjoy the most about the work that you do?

Gregory:         That is an incredibly difficult question. I am a physician, and I directly care for patients one-on-one throughout most of my day, whether that's in the context of research or in straightforward clinical care, and that's incredibly rewarding. But on the other hand, the ability to help move innovative ideas forward, to be at the forefront of our search for cures for a disease as devastating as Alzheimer's disease, is incredibly intellectually rewarding. That combination is something I simply wouldn’t trade in for anything.

Tom:              Dr. Gregory Jicha, chief clinician and professor at the University of Kentucky Alzheimer's Disease Center. Thank you so much for your time.

Gregory:         Thank you for having me.

Dr. Gregory Jicha spoke at ONE: The Alltech Ideas Conference(ONE18). Click the button below to see presentations from ONE18: 

[DUNBOYNE, Ireland] – Alltech’s European Bioscience Centre, located in Dunboyne, County Meath, has been nominated for a US-Ireland Research Innovation Award. The centre has been nominated in the Multinational Corporation Category for research on how reduced diversity among intestinal gut microbes can affect animal health and can lead to the overgrowth of pathogens and the development of resistance. It also examines how increasing gut microbial diversity through nutrition and diet can aid in the control of these issues with the aim of reducing reliance on antibiotics.

Now in its fourth year, the awards are a joint initiative between the Royal Irish Academy and the American Chamber of Commerce Ireland and are aimed at recognising excellence in research innovation, creation and invention by an organisation as a result of U.S. foreign direct investment in Ireland. The winners will be announced on 18 May at the Chamber’s annual dinner, which will also welcome Minister for Business, Enterprise and Innovation Heather Humphreys.

Dr. Richard Murphy, research director at the Alltech European Bioscience Centre, said the nomination was a fantastic achievement for the research team.

“At Alltech, we strive for success,” said Murphy. “Our innovative solutions and cutting-edge technologies deliver real results for our customers and farmers, and so this award is a tremendous achievement for us as a research team. We are delighted to be nominated for a US-Ireland Research Innovation Award. This is a true testament to the hard work our team in Dunboyne put into researching innovative farming solutions.”

Alltech Ireland has long been a leader in both the Irish and European agriculture industry. Located in Dunboyne, County Meath, it became the first Alltech office to be established in mainland Europe in 1981 and today serves as Alltech’s European headquarters and bioscience centre.

Alltech’s European Bioscience Centre is Alltech’s pivotal research centre in Europe. The research work carried out at the centre specialises in cellular biotechnology, and the team of 20 scientists based in Dunboyne have developed unique insights into specific focus areas such as yeast cell wall architecture, trace element chelation, biomarker detection and microbial population dynamics. This work has resulted in the development of new solutions, services and analytical tools that improve producer profitability and efficiency.

“We have approximately 20 full-time scientists on-site in Dunboyne,” said Murphy. “We are very proud of our highly educated team and close links with Irish universities. The majority of the team have earned their Ph.D. or master’s degree with Alltech.

“Since redevelopment work on the facility was completed in 2013, the team at Alltech are very lucky to work in labs of exceptional quality and standard, thanks to Mrs. Deirdre Lyons, Alltech’s director of corporate image and design, who is responsible for designing our labs,” he continued. “This enables us to provide a state-of-the-art platform that enables young scientists to work with Alltech's expert team of biochemists, microbiologists and nutritionists.” 

Alltech’s European Bioscience Centre is one of the company’s three major bioscience centres around the world, with each centre having its own innovative focus. The centres are complemented by more than 20 research alliances with leading universities around the world. Alltech’s research team are also responsible for over 500 patents awarded to Alltech globally.

The following is an edited transcript of Tom Martin’s interview with Dr. Kristen Brennan, a research project manager at the Alltech Center for Animal Nutrigenomics and Applied Animal Nutrition in Nicholasville, Kentucky.

Click below to listen to the podcast:

                                    Dr. Kristen Brennan is a research project manager at the Alltech Center for Animal Nutrigenomics and Applied Animal Nutrition in Nicholasville, Kentucky. In this interview with Tom Martin, Brennan helps us gain a better understanding of her field, nutrigenomics, and its role in sustainable agriculture.

Tom:                            What is the science of nutrigenomics?

Kristen:                        The easiest way to think about nutrigenomics is to break the word down into what it is: “nutri" and “genomics.” What we're aiming to study with nutrigenomics is how nutrition — whether that’s nutrients, forms of nutrients, diets, timing of diets — influences the animal's genome. So, we’re not changing the genome, but influencing the activity of all the genes of that animal’s genome.

Tom:                            Is this an outgrowth of the human genome project, or has it been around a lot longer than that?

Kristen:                        Nutrigenomics is something that's been around forever. From the time the first living organism evolved, it needed nutrients, and those nutrients had influence on the activity of the genes within that animal or cell. The thing that we've done within the last several years is to figure out how to capture that information. It's always been there, we just never had a way of measuring it before. Technologies like genome sequencing are the core foundation for measuring what we're seeing.

Tom:                            Is there a point in time when we realized that nutrients were having an impact on genetic expression?

Kristen:                        I think we’ve known for a long time the importance of nutrition. Centuries and centuries ago, they had an idea that nutrition had a vital role. I don't know if we knew at that point, really, what DNA was and what genes did, but we knew that nutrition could influence the outcome, or a phenotype of an animal — what we're seeing on the outside — and how important it was for good health.

Tom:                            What are the advantages of nutrigenomics in animal studies?

Kristen:                        What I think makes this field so exciting is that, first of all, when we’re dealing with actual sampling, we need a very small sample amount. We can do this with, for instance, a small draw of blood from an animal, or we can take a small biopsy. So, you're not having to euthanize an animal to get tissue.

                                       Even more of an advantage is the amount of information we get. If you think about most genomes, you're talking about thousands of genes. We can measure in a single snapshot how every one of those genes is behaving in response to a diet or nutrition. That is an amazing amount of information.

                                       The other advantage is that it can be really rapid. From the time we get a sample to the time we have an output of data, it can be as short as just a few days in the lab. So, a lot of information, small input and a ton (of data) in a very rapid way.

Tom:                            And are you able to understand why some animals respond differently than others to the very same nutrients?

Kristen:                        Yes. We can use this information to understand that. An example would be healthy versus diseased animals and why nutrition may play a role in how they respond to that illness. More and more, we're starting to understand how differences on a genetic level — different breeds of animals, different production states, things like that — can influence how that animal responds.

Tom:                            Are you able to dig down into it and figure out how nutrients and bioactive components in the food turn on or turn off certain genes?

Kristen:                        Yes. The biggest amount of information we get is just a simple “Do they or do they not turn genes on or off?” So, how does each individual gene activity respond to what you're feeding? As we’re understanding that more and more, we can take a step back and start to understand how they're doing it. They are what we call signaling pathways, which are like, if you set up a row of dominoes and you hit the first one, it sets everything off. It’s the same thing with gene activity. There is a series of molecules that are responsible for regulating or activating other ones. And we can start to decipher how we get from the nutrient that we’re feeding or the diet we're feeding to that endpoint, that last domino in the line.

Tom:                            You can actually target issues that call for some kind of nutritional intervention?

Kristen:                        Yes. And that's obviously one of the most exciting applications of this research. We can use this to define precision nutrition.

                                    One of the challenges with feeding animals, or people in general, is that there are so many environmental factors that influence how an animal responds to diet — things like illness and disease, but also production state, where they're living, what their basal diets are. And so, we can use this technology to get precise information on how we can use nutrition to get the best performance or best health out of that animal.

Tom:                            How do you carry out your research? What goes on in Kristen Brennan’s laboratory?

Kristen:                        It’s magic! This research is done in several steps. It’s really a team effort. The simplest study we have is between two groups of animals, and because so many things could influence gene expression, we want to make sure that those two groups of animals are as identical as possible — same breed, sex, age, production state, and they’re housed in similar environments. The only thing we want different between those two groups is the nutrient we’re interested in.

                                    For instance, if we’re looking at a form of a mineral like selenium, we might have one diet that contains selenium in the form of sodium selenite, and we might have the exact same diet for the other group that has selenium in the form of organic selenium like our Sel-Plex® product. Once we have fed these diets for a given amount of time — it just depends on what we're interested in looking at, what tissues and what nutrients we’re evaluating — then we obtain a sample. It can be as simple as just a very tiny muscle biopsy or a few milliliters of blood. We bring that to the lab, and our laboratory technicians will essentially take that tissue, rupture the cellular membranes and then the nuclear membranes and purify what we call the mRNA, or the transcripts, that are located within the nucleus. We make sure that transcript, or a total RNA, is of super high quality and purity because these assays are so precise. We have high standards for what we can use.

                                       And then we use a commercially available DNA microarray. And what that allows us to do is profile. It has probes for each gene on the animal's genome — for example in the case of a chicken, it has something like 18,000 probes — and that allows us to measure whether the mRNA, or the transcript, for each of those genes has been increased or decreased in response to the nutrient that we fed.

                                       At the end, we get a long spreadsheet that says gene A is increased, gene B unchanged, gene C is decreased.

                                       Then the tough part comes, and that is the data analysis. So, we have all of these data points — you’re talking about thousands — and it is sort of like taking one of those huge puzzles. If you took that box of puzzle pieces and threw it on the ground, you would just have a giant mess, right? When I get that Excel spreadsheet of thousands of rows and columns, that’s what it’s like, essentially. So, we need help to try to piece those puzzle pieces together. If we took one piece out, we might find a corner and that's really important. Just like if I look at that spreadsheet, I might find a gene that's very important, that's very highly increased or decreased. That's a starting point.

                                    What we really need to do to see the big picture is piece those puzzle pieces together. We use what we call bioinformatics — essentially biological statistics — and we use software programs that say, okay, these 100 genes are related, they all have a common biological function, and based on their activity, we predict that biological function to increase or decrease. And that helps us make sense of this information.

                                    So, just like piecing those puzzle pieces together, we get that big picture of what's going on inside an animal that results in what we're seeing on the outside like improved growth, or improved feed efficiency, or improved markers of health.

Tom:                            I'm under the impression that the “Holy Grail” for you would be to find and establish a link between nutritional genomics approaches and applied nutritional research. Can you explain?

Kristen:                        Sure. The ultimate goal, at least in my view, for nutrigenomics is when we do traditional nutrition studies, we take an experimental diet, we feed it to an animal and we look at a phenotypic output. So, what do we see in the whole animal? That might be body weight change, growth rates, feed efficiency — things we can measure in the whole cow or by just looking at the animal. We might look at blood markers, stuff like that. What often is lacking and what we can use nutrigenomics for is, how do we get from point A to point B? How do we get from feeding this diet to the response in the whole animal?

                                       What nutrigenomics gives us is a tool to look at a molecular reason for those changes. We can use nutrigenomics to figure out, are we affecting energy expenditure in the cell? Are we affecting protein translation in the muscle? Things like this can help us explain what we're seeing in that animal instead of just guessing on how something works.

Tom:                            Does this technology, nutrigenomics, reduce our reliance on large-scale animal studies, and is it less invasive than the traditional approach?

Kristen:                        I think so. When we do these studies, we can work with a much smaller number (of animals) per treatment. So, where you might need hundreds of animals to get, say, carcass quality measurements that are significant, we can use six or 10 animals per treatment and still get some of the same information that would explain why we see changes in a large animal. Obviously, they're complementary, but we use this technology to minimize the number of animals we need per treatment.

                                      The other advantage is the obtaining of samples. We don't need a whole kilo of skeletal muscle to do our analysis. We need a tiny amount. So, that really is noninvasive. We can use a simple blood draw that is noninvasive and get this information out of that.

Tom:                            The 21^st century farm is a changed place compared with that of the previous century. A big reason for that is the arrival of a lot of science, technology and big data. If we were to take your science, nutrigenomics, out of the laboratory and into the farm, how would producers use what you've learned?

Kristen:                        I think one of the major ways they can use it is precision nutrition — really formulating diets to meet the actual needs of an animal. And also to understand the form versus function of different nutrients. So, how do we get the best that we can get out of an animal through nutrition? Nutrigenomics gives us that tool to understand how.

Tom:                            To carry that further, beyond helping to determine what will work for an animal's genetic type, is nutrigenomics helping explain why we need to find what works for a given animal?

Kristen:                        Absolutely. And I think it really helps push the idea of precision behind nutrition. For so long, we've overfed nutrients. We haven't really paid attention to form versus function. Nutrigenomics is giving us reasons why form is so important in nutrients, and why precise levels are important. We're taking the guessing game out of animal nutrition.

                                       I think as our population grows and the need for food continues to increase, that really optimizing nutrition based on an animal’s genetic potential is going to be really, really important.

Tom:                            How can this genomic information help us better understand nutrition and nutrient science?

Kristen:                        That’s a great question. This gives us a good understanding of the hidden effects of nutrition — the things that we don't really understand; why we see the changes. Why are we seeing increased energy efficiency with different forms of selenium, for instance? If we just look at our traditional nutrition research, we have no idea. But we use nutrigenomics to say, “Okay, well, the genes that control, say, mitochondrial growth in the skeletal muscle in the animals are turned on by Sel-Plex, and that explains why we see changes in energy expenditure.”

                                       That’s the type of stuff that we can get through traditional animal nutrition research, and nutrigenomics really helps push that information ahead and gives us a better understanding of how nutrients function — things that we can't see by just looking at an animal.

Tom:                            One final question: Among the things that you're working on right now, what really interests you and excites you?

Kristen:                        Everything, as a true scientist! One of the areas that I'm completely fascinated by, and have been for years — and we've done quite a bit of work on it, but it's just something that I start to think about and almost gives me a headache — is the idea of nutritional programming. This is the concept of how early life nutrition — whether that's in a neonatal animal or even in the gestating diet, looking at offspring — how nutrition early in life influences an animal throughout its lifespan.

                                    We've done a lot of work to look at some of the things that happen, like gene expression changes that occur. When we change the diet of an animal in the first 96 hours of life, those patterns and the changes stay with that animal throughout its lifespan, and that completely fascinates me.

                                       I think that's an application that is something that can be applied through all different species of animals, whether that’s livestock or even humans. We think about how you are what you eat, but you're also what your mother ate and what her mother ate and then maybe what her dad ate. It starts to really fascinate you. So, that’s probably one the most exciting areas that we work on.

Tom:                            Dr. Kristen Brennan is a research project manager at the Alltech Center for Animal Nutrigenomics and Applied Animal Nutrition in Nicholasville, Kentucky. Thank you for joining us.

Kristen:                        Thank you.

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