Narrator:

Introducing Doctor Fontecha, a distinguished researcher at CSICs in Spain. Doctor Fontecha's research involves fortifying foods with lipid components such as omega three conjugated linoleic acid, phospholipids, and sphingolipids. Known for their high biological activity. Doctor Fontecha currently leads the Lipid Biomarkers in Food and Health group at the Institute of Food Science Research in Madrid, and his research focuses on preventing cardiovascular disease, age related cognitive decline, and enhancing cognitive development in newborns and infants through dietary interventions. Please welcome Doctor Fontecha.

Doctor Javier Fontecha:

Hello everyone. Welcome to Madrid. I hope you enjoy Madrid. It's a beautiful city I live here. So this is the city for the Real Madrid. We say the best team of the world. So thank you to the organizers for inviting me. It's a pleasure. And, Let's see. if the presentation is coming. Okay, great. I'm going to talk to you today about the feeding the brain recent nutritional strategies with a special interest in the milk fat globule membrane.

This is an area which we are working for more than 15 years now. So this is the presentation outline breast milk, breast fed versus formula fed baby human MFGM versus cows, cow’s milk. Scientific advances and benefits of MFGM. Some of our recent studies and final consideration. Well, in the last session it had been talking about the composition of breast milk. We all know that it's very complex and, very dynamic because it's changing as Doctor, Collado said is changing almost every day. And we have here colostrum, transitional milk, mature milk. And the composition is very, very dynamic. So this is the reason that this very, very difficult to mimic in infant formula. But we have some different components like in colostrum oligosaccharides.

It goes to directly to the immune and brain development. And also we have oligosaccharides, proteins, lactose, taurine, and fats. We work in fats long chain PFAS first one is Sphingolipids which are also going is going directly to the brain and cognitive development. So we know we all know that the infant formula is very important when breastfeeding is not possible.

But of course clinical study says that breastfeeding has very, very very amount of benefits against the infant formula. It has different growth patterns, better cognitive achievements, fewer infections, etc.. So our hypothesis is that maybe or some of these benefits are coming from the milk fat and of course from the milk fat globule membrane. Because in infant formulas they take out the milk fat and they put vegetable oils, so the matrix, the components are very, very different. If you see here in this maker photograph you see all the milk Fat globules are very different in size. We don't have time. But the size is also important for the composition. And we have here the milk fat globulel membrane which surrounds the milk fat, protect the milk fat and secure the delivery of this fat to the baby.

But the milk fat globulel membrane is not only for protected milk fat is also very important because confers bioactivity and health promoting properties to the fat fraction of the milk. We'll see that later. So here we have a very nice picture of the milk fat globulel membrane. This is a three layer with one inner inner membrane that comes from the endoplasmic reticulum of the cellular.

The gland cellular. And also we have the bilayer full of phospholipids and a sphingolipids and glycoproteins. And we see all the functions, the proteins that are in the membrane. They are like a xanthine, butyrophilin  and antibacterial properties regulate lipids secretion T cell proliferation and metabolism. And also we have glycerol phospholipids, PE, PC, PI, PS  and phospholipids that are very important. All these red and yellow balls are phospholipids in the membrane. And this is, important for cell development, function and integrity, brain development and function. Intestinal mucosa barrier function and role of physiological and biochemical process. But we have a glycolipids also there that are very important for the brain. This is a regulation on immune cells brain development brain development and function with a sphingomyelin sphingomyelin.

See here. This is a special structure that we call lipid wraps. That wraps is this section of the sphingomyelin which is very rigid structure with a cholesterol which is this yellow squares. This is conserved. It's a very conservative area during evolution. So this is very important for brain development. And also we have glycoprotein glycosylated proteins that are some when using way like tethering they have a role in gut immunity digestive enzymes induction as anti-inflammatory.

They have a lot of properties. So that milk fat globule membrane is a very important component in the breast milk. But how are the lipids in brain. We know that the baby these triples is three times higher during the first years. The brain and it is full of lipids. More than 60% of the brain is lipids. And two thirds of these lipids are polar lipids.

So this is very important to get the brain connectivity and communication. And here all the polar lipids that we see we have in the milk fat globule membrane that are making a very important function in the brain. We have all the phospholipids PC, PI with major constituents of all the membranes, the neurons, the astrocytes. We have the sphingolipids important for neurogenesis, all the glycerol phospholipid and of course cholesterol, which is also very important for synaptic connectivity in the brain. So all these components are in the MFGM. This is a very nice picture. This is made by my coworker Antonio Pérez-Gálvez. Here you see this is a very nice because is that way they say mother child link is the milk fat globules come with the maternal epithelium in the mammary gland cells goes to the milk to the breast milk, and after that after newborn digestion the all the milk fat globules with the milk fat globule membrane goes to the epithelium of the newborn and the fat goes to the epithelial cells.

And the milk fat globule membrane stick there in the membrane of the epithelium are all these phospholipids. Glycol lipids like glycoproteins stay in the epithelium of the newborn, so they protects the immune system. So as a summary we see here in this graph  the MFGM affect multiple health systems in the infant the intestine and MFGM interacts protecting the infant from pathogenic bacteria in brain.

MFGM provides many components and we see before and in metabolism we have a MFGM also that contains all the components. That is very important to the metabolism and health of the baby.

But what happened with the composition of the MFGM, well we are studying in our lab, all these isolation, MFGM, we are able by different techniques to isolate the MFGM and from the milk fat globule. Also different companies have obtained MFGM and and now you can find commercially commercialized. So we can study the different components. We then define the different components the structure.

And now we know some of the functions of these components. So we have the lipids, the sugar, the proteins and all these bioactivities of these different components. And of course we are now working in the applications of this and this component in different products, but we don't know. Still, the molecular mechanism for MFGM, how the MFGM acts in our metabolism. So we are a study that in my lab we have this strategy. We start studying the food lipids mostly in dairy products. We obtain the lipids with potential metabolic bioactivity. We obtain. We isolate these lipids and we can study the lipids in the cellular metabolism. We can see the target the tissue target of these lipids. With preclinical studies in animals. And of course, when we have money enough we can study in humans, we can do the pharmacokinetic, we can do the bioavailability of this component. And of course, clinical studies. This study is very recent, very recent. We study the MFGM in colostrum in preterm and full term babies. And what we found is after obtaining the MFGM from the colostrum, we obtain the milk fat and the top of the tube and the MFGM in the bottom.

And we can study in different chromatographic equipments and we see all the profiles of fatty acids. We see the difference in between MFGM in the preterm and term babies, and also cholesterol and lipid classes in, lipid polar lipids. You see here the differences in cholesterol and three times higher in in lipid polar lipid in term babies. But the polar distribution it was more or less the same. So at the end we know that the composition of MFGM of human colostrum is affected by gestational period with different concentration of polar lipids cholesterol, arachidonic acid, DHA, all of them directly involved in a cognitive development of newborn, probably because the mammary gland would, when preterm is not fully develop.

This is one of the question always the people do how similar is MFGM in human milk and in cows milk? What you see here in this graphic how with different colors, the polar lipids and you see very, very similar you have phosphatidylcholine, phosphatidylethanolamine  phosphatidylinositol, the sphingomyelin in yellow in yellow phosphatidylserine, in human milk there are a little more sphingomyelin and phosphatidylserine than in MFGM in bovine but is very very similar in composition. Nevertheless when you would use another vegetable oils as a soy or sunflower, you see the differences are very, very high here you cannot find this sphingomyelin. And phosphatidylserine even in other lesser things of eggs are the composition is very, very different.

So now we can isolate MFGM from different sources like a buttermilk beta serum or cheese whey MFGM different companies say they are doing that. They obtain amounts of MFGM and from different sources. We are working in buttermilk. We obtain MFGM and enrich it ingredient. Then we can add some different foods like infant formula and then start to study the comparison between MFGM infant formula versus breast milk versus a standard formula infant formula, and see what the functional effects are infection cognitive achievement, etc.. And here you have on a recent paper like a look at the title MFGM as a possible panacea for neurodevelopment, infection, cardiometabolic disease and frailty. So all the clinical studies with different subject periods of study and MFDM supplements from different brands and all the outcomes, all of them positive. I like this study in infants, which is they have a longer period of study.

This study I don't want to talk too much because is John Colombo which is this a study of John Colombo. Yeah. He will talk about these but just some results. You see that red bars is the supplemented infant formula with MFGM and lactoferrin in all of them. It was a high impact in the cognitive area of the babies. When these infant formula were were supplemented with MFGM and lactoferrin. Now in our lab we are studying the effect of MFGM during aging. When we get older, we can we have some experiments with aged rats and also with humans. And we are trying to see the MFGM supplement can improve the mild cognitive impairment during aging. Here is now this cure now this this cure this. We have age associate memory impairment that it goes down. This is normal. We all when we are getting older, we are losing memory. This is normal. But if you go for the preclinical signs you have mild cognitive impairment, even dementia or Alzheimer's disease. And these cures could be related with the loss of phospholipids in different regions of the of the brain, like, frontal white matter, temporal white matter, frontal cortex, temporal cortex.

In all cases, when we are getting older, we are losing phospholipids. So the question is, will we use MFGM to prevent the progression of mild cognitive impairment during aging? We are doing this time, this, this kind of, studies using MFGM and from bovine milk. Because if you see the lipids we have in brain, in bovine milk and human milk are also very, very similar in this study, we did in in old rats we obtain MFGM concentrate.

We put it in supplementation food for the rats, and we give it this food supplemented with MFGM during 12 weeks. And we did the cognitive assessment. And you see here in red the supplemented and in blue the control rats. And here you see that the red line means that the these rats are making the exercise faster that the control. So they have an a spatial working memory faster. And also we study different regions in the brain and synaptosomes. And we found that the in this synaptosomes we have higher content of EPA and DHA which is a longer chain fatty omega three and also higher amount of phospholipids. And finally, we did this study in humans, in people over 65 with a mild cognitive impairment.

And also with some people cognitively healthy. We use two formulas, one without MFGM and and the other and enrich it in MFGM. And after 12 weeks, we found significant increase in long term memory in the group of people that were taking supplements and also short term memory significantly higher in that people that was taking also the supplement. So the evaluation of cognitive function, attention, language associative function and memory indicate that the intake of daily dose of a product and reach it in MF GM correlate with a significant increase in short term and long term memory.

So some final considerations. MFGM is a complex structure with glycoproteins, phospholipids, sphingolipids, gangliosides, ceramides, which are essential essential molecules to promote neurodevelopment of the newborn. MFGM has unique bioactive properties and demonstrated beneficial effects for health protection against infections, powering the immune system, cognitive development in infants, and prevention of mild cognitive during aging. MFGM, enriched fraction from different origin, isolation process, and treatment may have different composition and bioavailability, and MFGM is safe. Clinical studies have demonstrated that MFGM consumption is safe, well-tolerated, and lacks evidence of adverse effects. And finally, supplementation of an MFGM in dairy formulation will be an alternative way to increase health benefit in both infants and adults. I would like also to thanks my team. We are working in three different institutions with different products, and some companies are also helping us to take in samples. And that's it. Thank you very much for your attention.

Oh! Now we have a test for you. If you paid attention, you have to know if this is true or false. That's the question. Clinical trials suggest a significant role for dietary MFGM in neuronal development, gut maturation, and immune development. Is this true or false? The time is running. Now we see the results.  Zero Percent. Well, it was true. Of course. Okay, this is the this is the same question. Now supplement in polar lipids bridge more of the gap between formula feeding and breast feeding. This is true or false.

Now we'll see the answer.

Of course, is true. But we don't know the answer of the people. Okay, now, 87.76% of the people that made the answer correct? Yeah. So I think this is all I don't think oh, this is a new question. Okay. Clinical studies have demonstrated that MFGM consumption is safe, well-tolerated and lacks evidence of adverse effects. Is the true or false?

They're making the calculation.

Oh, look at that. 97.66. Okay, great for you. Thank you very much.