Cell membrane lipidomics: one of the most current and important tools for the molecular health

In recent decades the disciplines related to health and nutrition, thanks to molecular techniques, have made giant leaps forward. Lipidomics is one of them; it is one of the “-omics” disciplines (for example proteomics, genomics) that deal dynamically with the molecules that exist in living organisms.

Lipidomics studies molecules called “lipids”, which contain “fatty acids”, simply called “fats”. These elements are the fundamental constituents of the cell membrane, the envelope that wraps all the cells of our body, and are specific in quantity and quality for each tissue. Cells do not exist without the cell membrane but without fats the cell membrane does not exist. With this premise it is essential to know which and how many fats make up the membranes of our cells, in order to achieve and / or maintain their balance, a necessary condition to allow the efficient functioning of the whole organism.

Fatty acids of the cell membrane

In addition to the circulating fats (triglycerides are the most known), there are fats called phospholipids that are able to combine spontaneously to form the cell membrane. Each phospholipid then has specific structure and functions according to the fats present. The science of fats (lipidomics) dedicated to the cell membrane studies its structure, functions and variations that come about in various physiological and pathological situations.

There are two types of fat molecules:

– saturated fats, characterized by a linear, rigid structure, and can be prepared by the body (therefore be careful not to consume too many with the diet!);

– unsaturated fats, with a characteristic folded shape and in turn divided into two groups: monounsaturated and polyunsaturated (the latter are “the famous Omega”). Monounsaturated fats can also be prepared by the body while polyunsaturated fats are essential fatty acids, that is, Omega-6 and Omega-3 must necessarily be intake with food.

Fats are contained in foods (to find out more click here) as well as they are processed by the metabolism.

The fat composition is therefore a result of how lifestyle, diet and metabolic transformations are combined.

Cell membrane lipidomic analysis

Can we know how many fats and what type we eat with food? And especially if our body has deficiencies or excesses of fat?

Lipidomics has been dedicated to the development of the analysis of the cell membrane; an instrument that determines a real molecular profile (molecular fingerprint) of the individual. A cell representative of all the others present in the body or of the tissues that make up all the organs is required; the scientifically validated cell is the mature red blood cell. From numerous scientific evidences, the red blood cell membrane, having an average life of four months within the body districts, when it reaches 3 months of life is the suitable matrix for giving information on the general state of the individual.

The lipidomic protocol of Lipinutragen

Thanks to the LNG-R1 robotic equipment, unique Italian excellence in the world owned by Lipinutragen, supported in its realization by the CNR Researchers founding members of the Company, it is possible to isolate the reporter cell, meaning the mature red blood cell, without manual intervention. Starting from cell selection (mature erythrocyte), from a blood sample, and by performing operations of separation and chemical transformations, it is possible to obtain the lipidomic profile, that is, the composition in membrane fatty acids. To date, our laboratory is the only one in the world to carry out this sampling and processing process; the result allows the membrane profile to be used as a reliable and repeatable clinical data.[vc_row][vc_column][vc_empty_space height=”40px”][vc_separator][vc_column_text css=”.vc_custom_1580169543957{padding-top: 20px !important;padding-bottom: 10px !important;}”]To learn more, we recommend reading:

-> the short interview with Dr. Carla Ferreri >> https://www.lipinutragen.it/cos-e-analisi-lipidomica/

-> the specific article on cell membrane lipidomic analysis >> https://www.lipinutragen.it/en/lipidomic-membrane-analysis/

 

 

Article edited by the Lipinutragen Editorial Board

 

Photo: ©Romolo Tavani | @normaals /123rf.com

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At the end of this extreme summer of soaring temperatures, fires, collapsing glaciers, storm surges and tornadoes, we can finally admit that the climate crisis is already here.

Despite the targets set by the World Climate Agreements, we cannot wait any longer: we must all do our part. The good news is that, very often, everyday actions aimed at change do both the planet’s and the individual’s good, placing us in a win-win situation, i.e. where the benefits are for everyone.

This is the case in the area of food choices that have direct effects on both individual health and the environment.

“The food system is responsible for one third of global greenhouse gas emissions from human activities”.

This is the title of the recent report by researchers from the FAO and the European Joint Research Centre in Ispra.  The predominant contribution comes from agriculture and land use, while the rest is divided between supply chain activities and final food consumption. In detail, of a total of 17.9 billion tons of CO2 emitted into the atmosphere each year:

– 71% comes from land use (including deforestation and fires for subsequent agricultural exploitation) and emissions from cultivation (production and use of chemical and organic fertilizers), livestock farming, aquaculture and fuel used by agricultural machinery;

– 18% refers to the distribution chain, defined as all processes of industrial food processing, transport, packaging and retail distribution;

– 11% relates to after-sales, divided into food preparation (mainly cooking) and waste management.

Being sustainable is good for your health

The latest epidemiological data report that around 2 billion people worldwide are overweight or obese, while more than 800 million people do not have enough food to eat.  This shows that mankind has a problem with food that is multidimensional: the current food system not only has a significant climatic cost, but also has a strong impact on the health of the individual.

Given the enormous cultural, social, economic and landscape diversity, there is no single recipe to solve the planet-wide environmental crisis caused by food production. However, each of us can adopt virtuous behavior at the table that is beneficial to both the individual and the community.

• choose the short supply chain.

Favoring local production means maintaining agro food realities that have been part of the area’s culinary tradition for many generations, while at the same time promoting techniques of sustainable cultivation methods that respect the ecological balance in which the producers themselves live. This leads to a well-being of the economic, social and environmental fabric also for future generations.

• Choose meat from extensive animal husbandry.

For years, red meat has been demonized for its saturated fat content and its role in blood cholesterol levels. However, the lipid profile of meat can undergo important variations depending on the diet of the animal, defining (and improving) the saturated fat/unsaturated fat (MUFA and PUFA) ratio. Choosing meat from grass-fed animals not only means eating meat of a better nutritional quality (higher MUFA and PUFA fats, vitamins and antioxidants), but also decreasing the environmental impact of intensive livestock farming due to the production of soy and maize-based feed and the extremely high water consumption. So, yes to quality red meat, according to recommended consumption frequencies.

• choose sustainable fish.

Dietary guidelines recommend the consumption of fish, with particular reference to fish rich in omega-3 fats, for its health benefits. Nevertheless, it is not mandatory to consume only salmon and tuna. One can undoubtedly choose for locally caught species, diversifying their consumption to give them market value and avoid them being discarded once caught. So let’s go back to consuming ‘poor fish‘ such as hake, gurnard, mackerel, anchovies, mullet, sargo, sardines… as this can help maintain marine biodiversity and avoid the depletion of fish stocks of other species considered more valuable, such as tuna and swordfish. In addition, if the size of the fish in adulthood remains small to medium, it will have accumulated fewer environmental pollutants by the time it is consumed. Finally, species that reach reproductive age quickly are less at risk of extinction from commercial fishing.

• Consider alternatives to cow’s milk

Numerous alternatives to cow’s milk are now widely available. Commonly referred to as vegetable milks, these are beverages obtained by pressing oil seeds, cereals or pulses. The environmental impact of cow’s milk production is significantly higher than that of plant-based beverages in terms of greenhouse gas emissions, land use and fresh water use [4]. Therefore, if you want to reduce the environmental footprint of your diet, switching to plant-based alternatives is a good option. When choosing a plant-based beverage variety, along with one’s taste preferences, one should orient one’s choice according to the principles of lipidomic balance, knowing the lipid profile of each beverage in order to make a personalized choice according to one’s nutritional needs (here  our recent article on lipidomic comparison of plant-based beverages).

• Reduce packaging.

For every kg of plastic produced, 1.2 kg of CO2 is emitted into the atmosphere, not counting fuel refining and final waste management. If the absurdity and uselessness of much of the packaging we find in the supermarket does not make us think about the environmental impact, let us then think about the impact of plastic on our health. It is only in recent years that we have begun to talk about endocrine disruptors . These are substances that mimic or antagonize hormone signaling and, for this reason, have strong health effects depending on the age and sex of the individual. Immune, neuroendocrine, reproductive, and metabolic (“obesogenic”) effects have been documented following exposure during pregnancy, growth, puberty, and also on subsequent generations. Some of these compounds have long been used in the production of bottles, containers and food films. These are lipophilic substances (so beware of fatty food packaging!) whose effects do not follow the paradigm of toxicology: no dose-response curve or minimum toxicity value can be defined. Moreover, being highly persistent in the environment, exposure is never acute, but occurs over decades at very low doses, making it extremely difficult to establish a cause-and-effect relationship with hormonal and metabolic disorders.

• reducing household food waste

In the world, there is great inequality regarding access to food. On the one hand, in Western countries there is a high rate of over nutrition and consumption of ultra-processed food with low nutritional value, and on the other hand, in low-income countries, there is great insecurity regarding access to nutritious, safe and adequate food. Despite this, it is estimated that one third of all food produced is wasted because it is unsold or bought and not consumed. This waste not only directly affects the inequalities of the planet, but is equivalent to wasting the precious resources used to produce it, such as soil, energy and water. Reducing food waste may not at first glance have a direct impact on an individual’s health, but it does highlight selfish, compulsive behavior lacking social empathy that, if corrected, benefits every person within the community in which they live.

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References:

[1] Crippa, M., Solazzo, E., Guizzardi, D. et al. Food systems are responsible for a third of global anthropogenic GHG emissions. Nat Food 2, 198–209 (2021). https://doi.org/10.1038/s43016-021-00225-9]
[2] www.who.int/health-topics/obesity#tab=tab_1,
[3] https://www.issalute.it/index.php/la-salute-dalla-a-alla-z-menu/i/interferenti-endocrini
[4] https://ourworldindata.org/environmental-impacts-of-food#dairy-vs-plant-based-milk-what-are-the-environmental-impacts

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Article by the editorial team of Lipinutragen

The information provided must in no way replace the direct relationship between health professional and patient.
The food recommendations in the article are not intended as a substitute for a personalized meal plan and are to be adapted to specific cases.

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Photo: 123RF Archivio Fotografico: 69913899 : ©aamulya | Data source: Crippa. M., et al. (2021) Food system are responsible for a third of global anthropogenic GHG emissions. Nature food. Our WordlsinData.org – Research and data to make progress against the world’s largest problems. Licensed under CC-BY by the author Hannah Ritchie.

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The membrane, the cells’ gateway!

The human body is made up of billions of cells, all surrounded by a vital coating: the cell membrane. It is a complex mixture of fats in a fluid state, where proteins and another fat, well known to the public, cholesterol, are immersed.

The cellular or plasma membrane constitutes for the cell a coating that surrounds it but not an “isolation”, indeed it is the way of communication between cell and external, collecting and sending signals between the other cells of the same tissue and of different tissues distanced one from another, as well as the way of passage and exchange of nutrients necessary for the life of the cell itself.

The basic constituents that create the membrane structure are phospholipids, molecules composed of fatty acids with different chemical structures. Each organ, therefore each tissue, of our organism has the membrane that contains a composition of fatty acids, equal in type but different in quantity from fabric to fabric, creating a real identity card, which allows recognition but which above all allows the adequate functionality of that organ. (1)

Although very briefly, what has been mentioned on the cell membrane shows how this compartment is fundamental for the life of every human being and how its composition is information to be acquired and deepened regarding the correct distribution of the various types of fatty acids.

Chemical “bonds” make the difference

Fatty acids, based on their chemical structure, are divided into two large families: saturated and unsaturated. Saturated fats have a linear structure and participate in the construction of the cell membrane giving it stability and rigidity; unsaturated fats have a more flexible structure, with one or more folds (called unsaturation) which results in the construction of a more fluid and permeable membrane. Due to the presence of both types, the membrane is in fact an alternation of more rigid and more fluid areas, each with its role in the overall functioning of the cell. Based on the number of folds, unsaturated fats are divided into monounsaturated (a single fold) and polyunsaturated (multiple folds). (2)

In addition to being present in the diet, saturated and monounsaturated fatty acids are constantly produced by our body through specific “metabolic machines”, called enzymes. As for the production of polyunsaturated fatty acids, it starts from precursors that the human body cannot build independently, since it does not have the necessary enzymes. This determines the absolute need to introduce polyunsaturated precursors from the diet, which are called essential fatty acids. Subsequently, the entire series of omega-6 and omega-3 polyunsaturated fats will be formed from the precursors. The composition of the cell membrane is obtained, therefore, both from the work of our body’s “metabolic machines” and from fats, which should be mainly polyunsaturated, which we introduce with food every day. (2)

We are the architects of the correct composition of the membrane, choosing what we bring to the table every day

The well-being essential balance

]The composition of the cell membrane reflects the food lifestyle and the body’s metabolism. It is necessary to pay particular attention to the choice of fats and keep in mind the indispensable role that Omega-6 and Omega-3 polyunsaturated fatty acids play as structural and functional elements of the cell.

Polyunsaturated fatty acids or PUFA are of two types: Omega-6 and Omega-3.

PUFA Omega-6: this family has the negative reputation of being “pro-inflammatory”, because among its components there is Arachidonic Acid, protagonist of the inflammatory reactivity of our body. This negative meaning is incorrect if we consider that inflammation is not actually a harmful process, but it is the response of our body that “must solve a problem”; the problem arises when the inflammatory process, which is triggered in the cell to defend it, cannot turn off properly. Another point that does not justify the bad reputation of omega-6 PUFAs is represented by the activity carried out by some of its components, including DGLA, a very important omega-6 fatty acid implicated in anti-inflammatory and immune processes. For further information >> https://www.lipinutragen.it/en/dgla-at-the-crossroads-of-pro-and-anti-inflammatory-processes/

PUFA Omega-3: its best known components are EPA and DHA, long chain omega-3 fatty acids, which participate in the fluidity of the membrane and are important constituents of the cell membrane of the nervous system and the retina, especially DHA. EPA is a precursor of molecules with different activities, the most important being the anti-inflammatory one which balances the reactivity implemented by Arachidonic Acid, and together with DHA they promote the resolution of inflammatory processes in all tissues. For further information >> https://www.lipinutragen.it/en/omega-3-dha/

The Omega-6 and Omega-3 tracks, in addition to having essentiality in common, share the “enzymatic machines” which provide for the metabolic transformations of the various components of the families; the contribution from the diet must be balanced, without excess of one or the other family, to ensure the cell membrane the structural and functional balance that it needs. (2)

Food choices (including supplements) as needed

From this brief examination it is clear the need to know the composition of our cell membrane, to find out if there are deficiencies or imbalances, and to target the food choice in order to ensure balance. Being aware of your molecular state and taking care of it is simple, and it is lipidomics that can give us the answer in a personalized way: the ideal tool represented by the Lipidomics Analysis of the red cell membrane allows you to understand how the cells of our tissues are forming their own membrane in consequence to daily choices, nutrition and metabolism.

After the result of the analysis, there is the possibility to find out the diet and possibly the necessary integration to the identified needs, therefore to implement a personalized strategy, coined by us with the term NUTRILIPIDOMICA.

Read more about the cell membrane lipidomic analysis >> https://www.lipinutragen.it/en/importance-of-lipidomics/

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Bibliography:

1. Harayama et Riezman. Understanding the Diversity of Membrane Lipid Composition. Nat. Rev Mol. Cell Biol. 2018, 19, 281-296
2. Cell membrane and lipidomics. Carla Ferreri and Chryssostomos Chatgilialoglu. 2014, CNR Editions

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Article edited by the Lipinutragen Editorial Board

The food recommendations in the article are not intended to replace a personalized food plan and are to be adapted to specific cases.

Photo: 123RF Archivio Fotografico: 68438093 @Oleksandra Naumenko /123rf.com

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Motor activity is medicine

In the 4th century B.C. Hippocrates included gymnastics in conservative, i.e. preventive medicine, the concept behind today’s lifestyle medicine, codified in the U.S. and exported all over the world.

Doctor Girolamo Mercuriale from Forlì sanctioned the origin of medicine sports in 1569 with his famous treatise “De arte gymnastica” (1) which constitutes a bridge between the classical Greek-Roman era and the Modern era.

 

«Gymnastic science is the discipline that contemplates every type of physical exercise, reporting its specific properties, and has as its aim the preservation of good health and the acquisition and preservation of a perfect physical constitution».Approaching our times, one of the first studies that empirically correlates physical activity with human health dates back to the 1950s with the connection between cardiovascular diseases and the performance of active or sedentary work duties (2).

Over the years, a huge amount of scientific evidence has been collected on the positive effect of physical exercise in the prevention and treatment of the main chronic diseases, psychic diseases such as depression, on the reduction of the risk of death and longevity. Physical activity goes beyond the concept of “polypharmaceutical” (3), with respect to which it can be even more powerful, including among its effects also the reduction of low-grade inflammation that we remember plays a role, among other things, important in viral infections.

Skeletal muscle can therefore be seen as an endocrine organ capable of producing hundreds of myokines including growth factors, metallopeptidases, cytokines, etc. This secretory capacity increases with contraction, with muscle remodeling and in post training myogenesis.

Are the Italians sedentary or sporty?

An ISTAT survey from 2016 draws a national framework divided into two macro groups, sporting and sedentary, in more detail:

• about 25% of sports, that is, they carry out physical activity on an ongoing basis;
• approximately 35% physically active, that is, they do sports occasionally or do some random physical activity;
• about 40% sedentary, that is, they do not practice any sport or do physical activity or heavy work.

50 years ago only 7% of Italians practiced a sport (mostly hunting and football), but the days were characterized by a very active lifestyle, in children with outdoor games and without the pervasive presence of TV screens , PC or smartphone, in the means of locomotion and in the job duties in adults. With economic development, sedentary lifestyle has increased incredibly, but sports in leisure have also progressively increased. Nowadays, in fact, the percentage of sportsmen has risen to 60% with the prevalence of gym activities, fitness, running, following football, swimming and finally the other sports in lower percentages.

The growth of the sporty population is perhaps linked to the atavistic need to move one’s body or even to counteract the increase in obesity and related diseases. The fact is that more and more people wear sneakers and tracksuits during the week to carry out some activity.

Sport: at what time of the day?

To get the maximum benefit from physical activity, it must be entered correctly in relation to meals and times of the day. This could contrast with the approach you have given to your day which does not take count the needs of human physiology. We must first of all remember that being diurnal animals the activities of maximum commitment and effort must be carried out in the morning or in the central phases of the day. Synchronization with circadian rhythmsis essential to work efficiently and effectively on our body.

The normal caloric intake

From a quantitative point of view, the athlete’s diet should be normal calorie, with a caloric distribution throughout the day, without skipping breakfast which, on the contrary, must be one of the main meals of the day.

Using the reading key of the autonomic nervous system (SNA) and the neuroendocrine axis of cortisol (HPA) we know that a cycle, such as a sinusoid, is naturally present in humans, which has a maximum in the early hours of the day and a minimum at late evening and early at night. Unfortunately, the modern lifestyle, with the lengthening of mealtimes and activities in the evening hours, has generated a desynchronization and flattening of these axes with tangible consequences on people’s energy status and resilience.

Why avoid dining late

For example, performing a workout at 7 – 8 p.m. or later will raise the SNA and HPA axes at a time of day when they should have gone down. The next meal will further raise the cortisol and “keep the insulin” awake all night, thus preventing other hormones, including GH and melatonin from performing their recovery tasks and having a natural and regenerating sleep cycle. This effect will be more or less marked depending on the qualitative and quantitative composition of the meal. (For insights>> https://www.lipinutragen.it/en/biological-clock-and-feeding/)

Food is energy

Another element to consider is the presence of fuel to support physical-motor activity. We know that muscle can use sugars or fats in a variable mixture. While the fat tank is almost infinite, the sugar tank, in the form of glycogen, is much smaller and more limited (about 500 g in the muscles and about 100 g in the liver). That is why before sport you have to start with glycogen stores in full muscles and liver, while the stomach must be empty in order not to have expensive digestive processes in progress.

For this reason, it is important to avoid long fasts and expertly introduce snacks, the composition of which will vary according to the time available before physical activity.

Clearly the issue is very complex and requires to be studied on a case-by-case basis and after an assessment of the body composition and individual tissue hydration status.

 

See also the article previously published for the interesting implications that emerged on the need for omega-3 in endurance sports> https://www.lipinutragen.it/en/lipidomics-for-athletes/

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Bibliography:

(1) Girolamo Mercuriale, De arte gymnastica. Ilte Industria Libraria Tipografica Editrice, Torino, 1960, 421 pagine, p. XIII
(2) Morris et al. Coronary heart-disease and physical activity of work. Lancet. 1953 Nov 21; 262(6795):1053-1057.
(3) Fiuza-Luces C. Exercise is the Real Polypill. 2013 Physiology 28:330-358.

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Article by:

Francesco Bonucci – Nutritionist

The diet advise, written in the article, are not intended to be a substitute for a personal nutrition plan and should be adapted to specific cases

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Photo: 123RF Archivio Fotografico: 52648870 ©udra /123rf.com

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Postpartum depression, get to know it and how to deal with it

Pregnancy is one of the most beautiful and expected moments for many women, the arrival of a new life and the direct perception of the future become a happy expectation for the woman , but the period after childbirth does not always represent a light period without frustrations and anxieties, which indeed they arise unexpectedly.

The Ministry of Health, in the Brochure: “Recommendations for your health and that of the child to come” defines the Post Partum Depression (PPD) as follows:

“It is a complex disorder that affects, with varying degrees of severity, from 7 to 12% of new mothers and generally begins between the 6th and 12th week after the birth of the child.

The woman feels sad for no reason, irritable and easy to cry, not good enough for the commitments that await her. In addition, a recurring feeling among new mothers who are faced with this problem is shame mixed with guilt. It is good to remember this: nobody are born parents, they become one.

The DPP represents not only a public health problem of considerable importance, given the social and employment implication it can cause, but above all an interference in the establishment of the mother-child bond. In fact, 67% of depressed mothers report difficulties in interaction and attachment. The reciprocity has been recognized as essential, capable of preventing the long-term consequences on the cognitive, social and emotional development of the child “

Everything points to the emotional sphere and brain functioning, so it was important to conduct research and establish what happens in the expectant mother, identifying that deficiencies may occur in the 9 months of pregnancy that make the balance of the maternal nervous tissue precarious¹.

What did the research establish?

Pregnant and postpartum women in most industrialized countries have a high chance of being deficient in Omega-3 for two general reasons:

• because in the usual diet there was a low presence of foods containing omega-3 (fish, oilseeds such as flax and hemp, walnuts, spinach etc…) ² essential fatty acids necessary for the functioning of all tissues (in particular the nervous one), and obviously even more important for fetal growth;
• because in the first two trimesters of pregnancy the biosynthesis and the accumulation of fats which are essential for building the cells of the fetal tissues are increased ³ and it is extremely important that the quality of these fats is well balanced precisely for the construction needs of all types of tissues.

Studying Australian mothers, dr. Rees and his team (2005)⁴, observed that babies need about 67 mg per day of omega-3 DHA for their development, but Australian mothers consumed around 15 mg per day – well below the required quantity. In fact, the various international food and health agencies indicate the omega-3 DHA quota of 200 mg / day as the reference daily intake, to be ensured during pregnancy (EFSA Journal, 2010). Mothers from countries like Japan, Korea or Norway, where fish consumption is naturally high, consume around 1,000 mg of DHA per day.⁵

The “shifting” effect of fats from maternal tissues to the fetus, in the event of a deficiency of essential fatty acids, will lead to an emptying of the quotas of essential fatty acids, precisely of the mother’s omega-3 type, including DHA, during pregnancy. This has been related to the increase in the incidence of depression that arises in the postpartum period⁶.

The influence of nutrition and intake of PUFA Omega-3 and Omega-6

Nutrition during pregnancy is a fundamental aspect; all the basic nutrients for the organism being to be formed must be provided by the mother, without neglecting the fact that a part must keep it to herself, for the proper functioning of her organism. Unfortunately, industrial food today does not help for a correct balance of nutrients in the dishes that we bring to the table.

Speaking of fats, considering the quantity and quality of the fatty acids introduced with the diet, the contributions have changed, and not for the better. Evaluating four generations, it can certainly be said that from the great-great-grandmother to the current mother all eating habits have considerably changed, and in particular it is known that saturated and omega-6 fats have increased, while monounsaturated and omega-3 fats have decreased⁷. Remember that omega-6 and omega-3 polyunsaturated fats (PUFA) are defined essential, because they must be taken in the diet and cannot be synthesized autonomously by the body. It is clear that if the recruitment promotes only one of the two types of PUFA, the situation at the cellular level is already in serious imbalance.

Especially for the cell formation required by fetal growth in the 9 months of pregnancy, an excellent availability of all types of fats must be ensured, especially those that cannot be prepared independently. Science has clarified that if the diversity of fats is not ensured, dysfunctions and problems occur at the level of all tissues, of processes such as recognition and immunity, of the metabolism and functioning of all systems, and this is a crucial topic for well-being. and the subsequent growth of the newborn ⁸. It is also worth mentioning that the fatty acids belonging to the omega-6 and omega-3 families play balanced and complementary roles, for this reason they must always be in a correct relationship with each other, which is ensured precisely by the balance in the supply. The omega-6 PUFAs’ are implicated in the inflammatory response processes and are counterbalanced by the omega-3 PUFAs’, implicated in the corresponding inflammatory resolution and neuroprotection processes ⁹.

DHA, the mother’s and unborn child’s friend

During the last trimester of pregnancy, the levels of proinflammatory cytokines, deriving from Arachidonic Acid (PUFA Omega-6), naturally increase in anticipation of childbirth. Inflammation has a positive purpose: to help the body prepare for labor. Other postpartum stressors, such as sleep deprivation, can also stimulate the production of proinflammatory cytokines, and it is necessary to know that there is a good presence of acids in the body omega-3 fats, with whom to counteract the reactivity effects of omega-6.

The omega-6 and omega-3 balance especially at the nervous tissue level is also necessary to obtain beneficial effects of the two fatty acids Arachidonic acid (omega-6) and DHA (omega-3) which are present in equal concentration in the neuron ¹⁰, a condition that keeps the response of these cells under control and avoids the process of neuro inflammation. The condition of neuro inflammation can be a problem not only for the correct neuronal development of the child but also for the condition of postpartum depression of the mother.

The witness of a mother who has made FAT PROFILE and a personalized lipid integration:

“As soon as I discovered being pregnant, I was” invaded “by a sense of responsibility that prompted me to refine and personalize the lifestyle, especially the food habits. I have made the chose that from that moment on I had to start making choices with the awareness that what I was doing had an impact on my child and his genesis and future growth. I could not be “selfish” in front of the phrase that the specialist who followed me, lipidomic referent, told me: do you know that at this moment of your life you are forming billions of cells? And that in order to be functional, cells must feed themselves on balanced components?

Well, it all started from these observations … what I was doing for myself, would inevitably affect my child. During the whole pregnancy I have followed the food directions literally (including taking supplements, customized month by month); in the post-partum period, with all the physical and psychological difficulties that a mother faces during her first pregnancy, I was able to quickly return to my initial condition and to face moments of fatigue and stress, always keeping a smile and adrenaline (typical of moments when you are happy and elated). “

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Bibliography:

(1) Opuscolo: “Raccomandazioni per la tua salute e per quella del figlio che verrà”. MinSal 2017
(2) GBD 2017 Diet Collaborators*. Health effects of dietary risks in 195 countries, 1990–2017: a systematic analysis forthe Global Burden of Disease Study 2017. Lancet 2019; 393: 1958–72
(3) Emilio Herrera and Henar Ortega-Senovilla, “Lipid Metabolism During Pregnancy and its Implications for Fetal Growth”, Current Pharmaceutical Biotechnology (2014) 15: 24.
(4) Rees AM, Austin MP, Parker G. Role of omega-3 fatty acids as a treatment for depression in the perinatal period. Aust N Z J Psychiatry 2005; 39:274–80.
(5) Kendall-Tackett, K. A. Long-chain omega-3 fatty acids and women’s mental health in the perinatal period. Journal of Midwifery and Women’s Health, 55(6), 561–567. (2010)
(6) Levant B. (2011). N-3 (omega-3) Fatty acids in postpartum depression: implications for prevention and treatment. Depression research and treatment, 2011, 467349.
(7) Simopoulos AP. The importance of the omega-6/omega-3 fatty acid ratio in cardiovascular disease and other chronic diseases. Exp Biol Met. (2008) doi: 10.3181/0711-MR-311
(8) Kabaran S. Besler HT. Do fatty acids affect fetal programming? J Health Popul Nutr. 2015 Aug 13;33:14
(9) Calder, P.C. Omega-3 Fatty Acids and Inflammatory Processes. Nutrients (2010) 2, 355-374.
(10) Bazinet et al;. Polyunsaturated fatty acids and their metabolites in brain function and disease. Nature Reviews Neuroscience (2014) doi:10.1038/nrn3820

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Article edited by the Lipinutragen Editorial Board

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Photo: 123RF Archivio Fotografico: 69978211 ©Antonina Vlasova /123rf.com | 137184772 ©nicoletaionescu /123rf.com

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Cell membrane and fatty acids

The fatty acids involved in the scaffolding of cell membranes influencing their guaranteed characteristics and efficiency in carrying out a specific activity (e.g. Muscle = Contraction).

The main families of fatty acids present in the membranes are: saturated fats (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA omega-6 and omega-3) organized in macromolecules called phospholipids [1].

In addition to having a structural role, fatty acids are used for energy purposes (e.g. SFA) and are involved in immunity and inflammation mechanisms, as in the case of PUFA omega-6 and PUFA omega-3. The last ones are called essential fatty acids; they must necessarily be in taken with the food as our cells cannot synthesize them, differently from what happens for SFA and MUFA.

The cell membrane is not only a static structure that delimits cells, but it is a very dynamic structure, which responds to the needs of the cell by providing immediately available fatty acids.

The membrane is able to respond to all internal (metabolic state, stress and inflammation) and external (nutrition, environmental factors) variations to which the cell is exposed.

Sport and lipidomics: “union is strength”

The membranes of an endurance sportsman, who follows training programs and carries out competitions that require prolonged efforts and solicitations over time, must be able to respond promptly to these stimuli, with a very intense turn-over of fatty acids.

With the lipidomic membrane analysis, performed on the Mature Red blood cell (mGR), reporter cell of the state of all tissues, the athlete’s metabolic and nutritional status is assessed.

The nutrition of a sportsman who does not provide the intake of PUFA (polyunsaturated) fatty acids, will cause a deficit in the membrane, which will not guarantee the correct exchange of fatty acids with a consequent slowdown in recovery times and cell regeneration, with a reduction in the performance or “overtraining” phenomena. The knowledge of the state of the mGR membranes represents, therefore, useful information to maximize the cellular response to physical effort.

The role of DHA in cycling

It is known that in physical activity, the organs that are most exposed to stress are the heart and muscles. From animal and human studies, it has been seen that the heart [2] and muscle [3] tissue are rich in DHA, omega-3 fatty acid, suggesting its central role in the physiology of these organs. Supplementation with fish oil (rich in DHA) has been shown to reduce heart rate and oxygen consumption used during submaximal effort (anaerobic threshold) in professional cyclists, with an increase in fatigue resistance [4].

Under this evidence, the Lipinutragens’ Scientific Team, has studied the effects of a training and an endurance race, in amateur cyclists, studying the membrane of their mGR (mature red blood cells) to identify the changes and the stresses caused by the intense physical effort.

The results of this study, published in the special journal of the “Journal of Strength and Conditioning Research” [5], show that, during a resistance training (2 consecutive training sessions of 100 km each) and an endurance race (cross-country ski race “Colle delle Finestre” from 96km), there is a change in the composition of the membrane fatty acids of the mGR measured before and after training and before and after the race.

In particular, it has been seen that:

• 86% of cyclists had a DHA deficit (compared to the normal values ​​observed in the Italian population [6]) even before training. This deficiency was even more evident after training;

• the depletion of DHA is even greater following a tender, with a reduction of approximately 2 times the DHA in the membrane (from 4.4% pre-tender to 2.4% post-race);

• a few weeks’ supplementation based on DHA (250mg / day) * is sufficient to bring the DHA back into the membrane to the optimal values ​​ (7.3% DHA after 9 weeks of supplementation).

In this study, a rapid change in the composition of membrane fatty acids has been observed, testifying to their dynamism in response to a sub maximal and maximal effort. In particular, there is a strong involvement of DHA, omega-3 fatty acid known to be involved in inflammatory and stress mechanisms, both intensified during the endurance effort and to a greater extent during the race, where the intensity of the effort requires an increase of Bio-available DHA (free DHA).

These membrane changes cause a lower efficiency of muscle and cardiac oxygen consumption with a decrease in fatigue resistance and a decrease in athletic performance.

The FAT PROFILE analysis to support sports

The lipidomic analysis of the mGR FAT PROFILE, with the above premises, is a useful and reliable tool for monitoring the balance of the membrane and for establishing a personalized lipid integration to be combined with nutritional advice and training techniques aimed at optimizing sports performance.

This information can be helpful, to all athletes and all professionals in the sport field, to start personalized integration plans by supporting the athlete during the competition periods and / or in the preparation phase, in order to guarantee maximum functionality of the tissue and avoid performance drops.

* COMPOSITION of the DHA-based product used
Commercial name: Li DHA
Composition: 250 mg DHA, 100 mg VITAMIN C, 10 mg VITAMIN E, 110 mg l-GLYCERYPHOSPHORYLCHOLINE, 2.5 mg Astaxanthin, 5 mg LIPOIC ACID.

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Bibliography:

[1] Ferreri, C. et al. Fatty acids in membranes as homeostatic, metabolic and nutritional biomarkers: recent advancements in analytics and diagnostics. Diagnostics, 2017; 7(1), 1; doi:10.3390/diagnostics7010001.
[2] Pepe S, McLennan PL. Cardiac membrane fatty acid composition modulates myocardial oxygen consumption and postischemic recovery of contractile function. Circulation, 2002; 105(19): 2303-8.
[3] Peoples GE, McLennan PL. Dietary fish oil reduces skeletal muscle oxygen consumption, provides fatigue resistance and improves contractile recovery in the rat in vivo hindlimb. British Journal of Nutrition, 2010; 104(12), 1771-1779.
[4] Peoples GE, McLennan PL, Howe PRC, Groeller H. Fish oil reduces heart rate and oxygen consumption during exercise. J Cardiovasc Pharmacol., 2008; 52(6), 540 – 547.
[5] Pierotti, S., Torquato, P., Larocca, A.V., Ferreri, C. Erythrocyte membrane DHA depletion after a gran fondo cycling race: A pilot observational case study. Oral Abstract presentation of XII International Symposium In Strength Training & Ironfemme Study. Journal of Strength and Conditioning Research. 2020, 34, 3, e262.
[6] Ferreri C., Chatgilialoglu C. Role of fatty acid-based functional lipidomics in the development of molecular diagnostics tools. Expert Review of Molecular Diagnostics, 2012; 12, 767-780

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Article by:

Pierangelo Torquato, PhD – Lipidomic laboratory director

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Photo: 123RF Archivio Fotografico: 31652560 ©neyro2008 /123rf.com

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Allergies, which is the cause?

It is well known that allergy, in its various manifestations, is rising all over the world, and involves the respiratory system, the skin and also the digestive system. In the late decades it has been a trend towards the growth of these diseases; alongside the percentage of subjects with an altered immune response, many scholars identify environmental pollutants (nitrogen dioxide, ozone, combustion gas) and pesticides used in agriculture that are ingested with food (raw fruit and vegetables) as responsible; by coming into contact with the immune system of the digestive tract, they are able to enhance the activation of Th2 Lymphocytes, triggering a hypersensitivity towards a series of potential allergens that leads to B Lymphocytes to produce IgE, immunoglobulins responsible for common allergic manifestations : rhino conjunctivitis, bronchial asthma, urticaria.

The use of medicinal plants in allergies

The medicinal plants that can be used during the allergic diseases are numerous; in this very short exhibition we will consider some of them, some of the most interesting and also some less known as an anti-allergic plant.

Blackcurrant: source of omega-3 and -6 polyunsaturated fats

Among these the best known is the BLACK CURRANT (Ribes nigrum L.) – FAMILY: Saxifragaceae (Grossulariaceae). The leaves (fresh or dried), the fruits and the seeds (oil) can be used.

Blackcurrant is a plant with multiple applications in phytotherapy due to the richness of the active components present throughout the plant: blackcurrant seeds are an elective source of polyunsaturated fatty acids. of the omega 6 series (especially GLA- linolenic gamma, 15%) and the omega 3 series saddle (ALA- alpha-linoleic 12-14%); GLA is a precursor of series 1 prostaglandins (PGE1) and ALA is a precursor of eicosapentaenoic acid (EPA), from which prostaglandins and thromboxane derive with anti-inflammatory, anti-allergic and anti-thrombotic properties. The seeds have also astringent properties due to the presence of tannins. The leaves, especially prepared as glycerin macerate, are used to counteract all general and local inflammatory forms, both of infectious and immunological origin, on the skin or on the respiratory tract. The phytocomplex of the leaves is believed to perform its activity by selectively stimulating the adrenal cortex which activates the anti-inflammatory mechanisms. The anti-inflammatory properties of the black currant are associated with the anti-allergic ones, on the basis of a desensitizing and immune stimulating action similar to that of cortisone. The fruit used as such raises the immune defenses due to the high content of vitamin C and is useful for vision due to the antioxidant and protective activity of anthocyanin glucosides. Currant has an excellent tolerance and does not present any particular contraindications to the recommended doses. It is recommended to use with caution in hypertensive patients. The oil from the seeds is not recommended in subjects treated with anticoagulants. Do not administer during pregnancy and breastfeeding.

PHARMACEUTICAL FORMS AND DOSAGE:
Fruits juice: 30ml / 3 times a day (anti-inflammatory)
Dry fruits: 300 mg / 1-2 cps per day (blood vessel protector)
Infused leaves: 2-4 g of powder in 200 ml / 3 times a day (diuretic, anti-inflammatory, anti-allergic)
Dry leaves: 200 mg / 3 vv per day
M.G.: 100 gtt (anti-allergic) or 50 gtt (anti-inflammatory) / 1 time per day or divided
Oil (seeds): 60-90 mg of GLA and 70-90 mg of ALA / 1 time per day

Ginkgo biloba: rich in flavonoids

In modern phytotherapy of allergic syndromes there is GINKGO (Ginkgo biloba) which belongs to the Ginkgoaceae family.

The Ginkgo is the only survivor of an order that was very common on earth until the Tertiary era. Fossil remains of Ginkgo biloba about 200 million years old have been found. The plant is very rich in flavonoids. The characteristic chemical compounds of this plant are diterpenes, better known as ginkgolids A, B, C, J and M, and bilobalide which inhibit the release of histamine by particular cells called mast cells. In addition, Ginkgo hinders the binding of PAF (Platelet Aggregating Factor) to cells in the bronchial mucosa, which is responsible for bronchial narrowing.

PHARMACEUTICAL FORMS AND POSOLOGY:
for the preparations the leaves are used, the standard extract on the market is EGB761, the daily dosage goes from 120 to 240 mg in the adult in one or two administrations away from meals. The intake is contraindicated in patients taking anticoagulant drugs, moreover it should be suspended in the 5-7 days before surgery and in the 2-3 days after surgery. Contraindicated during pregnancy and breastfeeding and has interactions with many drugs.

Liquorice: anti-inflammatory and anti-allergic action

Another antiallergic plant is the LIQUORICE (Glycyrrhiza glabra) – FAMILY: Fabaceae, of which rhizomes, roots and juice are used.

Liquorice has a prevalent anti-inflammatory and anti-allergic action and is also capable of inhibiting the release of histamine by mast cells. Use reserved for adults in contact dermatitis, in eczema, in some neuro dermatitis and partially in psoriasis, with an efficacy comparable to that of medium-power cortisone drugs.

PHARMACEUTICAL FORMS AND DOSAGE:
are based on dry extract nebulized and titrated in glycyrrhizin min.4% (X° Italian Pharmacopeia), whose daily dosage ranges from 6 to 8 mg. per kg of body weight, divided into two administrations, one between 7 and 8 o’clock and the other between 15 and 16 o’clock. Absolutely contraindicated in the hypertensive patient, in particular in case of hyperaldosteronism. It should never be associated with corticosteroids, except to consistently reduce the dosage of the latter, since it enhances their pharmacological action. It can potentiate the action of the following drugs: ibuprofen, warfarin, salicylates and deoxycholic acid. Associated with birth control pills, it enhances the hypertensive effect. It can increase sodium retention and the elimination of potassium caused by grapefruit juice.

Helichrysum: with antihistamine and antibacterial properties.

Finally, we report the HELICRISO (Helicrysum arenarium L.) – FAMILY: Compositae (Asteraceae) whose flowers are used.

The plant has antihistamine, anti-inflammatory, expectorant and antibacterial properties and can be used in the form of aerosols, eye drops and eyelid wraps in rhinitis, conjunctivitis and allergic blepharitis, in allergic respiratory diseases and in eczema.

PHARMACEUTICAL FORMS AND DOSAGE:
1 g of drug in boiling water for 10 minutes / several times a day, in mother tincture (30 gtt x 3 times / day) or in 8% cream or eye drops or in 1: 5 oil.

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Bibliography:

• Amellal M. et al. Inhibition of mast cell histamine release by flavonoids and biflavonoids. Planta Med. 16-19, 1985.
• Qaâdan F, Nahrstedt A, Schmidt M, Mansoor K. Polyphenols from Ginkgo biloba. Sci Pharm.2010;78(4):897-907.
• Olukoga A. et al. Liquorice and its health implications. J. R. Soc. Health 120, 83-89, 2000.
• Safayhi H. et al. Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase. J. Pharmacol. Exp. Ther., 261, 1143-1146, 1992.
• Scott GN, Elmer GW. Update on natural product-drug interactions. Am J Health-Syst Pharm2002;59:339-47.

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Article by:

Dr.ssa Rosaria Ferreri – Integrated Medicine Hospital Center AdlSudEst Tuscany

The information contained herein is provided for informational purposes only and is in no way a substitute for a doctor’s prescription or therapy.

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Are fats and autism connected?

To understand the correlation between fat and autism we need to touch on some general topics.
So let’s consider:

Topic 1: WHICH FATS ARE ESSENTIAL?

Fats synthesized as saturated, monounsaturated and polyunsaturated fats are all necessary in different proportions between them for the genesis and the development of the human cell. Some of them, called polyunsaturated fatty acids, are essential and are also known to the non-expert public as omega-6 and omega-3, because they must be taken through food and cannot be prepared independently by the cell itself. For the cells genesis, since fetal growth during the 9 months of pregnancy, an excellent availability of these fats must be ensured, especially of those that cannot be prepared independently. Science has clarified that if the diversity of fats is not ensured, dysfunctions and problems occur at all tissues’ level, of processes such as recognition and immunity, of the metabolism and functioning of all systems, and this is a crucial topic for well-being. and the subsequent growth of the newborn (J. Health Popul. Nutr. 2015, 33:14).

Fats are a well-known topic and their need is shared by all international agencies dealing with health and nutrition (World Health Organization, European Food Safety Authority). The intake of omega-6 and omega-3 (250 mg / day) must not be lacking for pregnant women or for infants and children and, remember, it must always be present also for adults.

Topic 2: THE IMPORTANCE OF FATS FOR CELLS OF THE NERVOUS SYSTEM

Fats form a necessary part of the cell which is the CELL MEMBRANE. No cell can exist without a membrane which is formed by a precise mixture of saturated, monounsaturated and polyunsaturated fatty acids for each tissue (Nat. Rev Mol. Cell Biol. 2018, 19, 281-296). Furthermore, precisely for the cell of the nervous system, which also allows to give the characteristic elongated shape and with many ends of the neuron, the presence of DHA (omega-3) and arachidonic acid (ARA, omega-6) must be guaranteed in equal proportion (see Figure).

This fat composition allows the insertion of other components, such as proteins, to allow the passage of ions (for example sodium and potassium). In conditions of normal composition, the brain cell is flexible and can be efficiently connected to other cells of the nervous tissue, to form a “latticework” that “turns on” and “turns off” allowing the passage of signals. Furthermore, for the cell of the nervous system, inflammation is a process that must be constantly under control, and this is achieved precisely through an adequate balance of omega-3 and omega-6 fats. A deficiency or excess condition of these two types of fats can cause malfunction of the nervous tissue, affecting learning and behavior processes for the worse, as well as aggravate a pathological condition (Int. J. Biochem. Cel Biol. 2017, 84:40 -45).

Topic 3: EVIDENCE OF THE ROLE OF OMEGA-3 IN AUTISM

Autism is a complex health condition that cannot be attributed to a single, prevalent cause. In addition to some genetic predisposition, environmental causes and various types of toxicity have been identified as factors concurrent to the occurrence of this syndrome (Dialogue Clin. Neurosci. 2012, 14: 281-292). The “puzzle” of contributions involved in this complex health condition requires a multidisciplinary approach by the doctor who evaluates it. Our research team at the CNR of Bologna collaborated with the children’s neuropsychiatric unit at the Maggiore Hospital of Bologna to determine the composition of the cell membrane fats in children suffering from autism spectrum disorder. We have examined the membrane of the mature red blood cell, which can be related to the condition of the membrane of the nerve cell, and – by means of an analytical, reliable and repeatable because completely automated processing procedure – we have determined the composition of the fats, showing the presence of some fundamental deficits. In two different groups of autistic children compared to healthy children, an omega-3 DHA deficiency (PLoS One. 2013 Jun 19; 8 (6): e66418; Sci. Rep. 2017, 7, 9854) was shown with a threshold of 4% below which the risk of disturbances increases 6 times. In addition, in this research the correlation between saturated fatty acids and cognitive difficulties was also determined, or an increase in behavioral manifestations typical of autism (PLoS One. 2013 Jun 19; 8 (6): e66418).

DHA is both an indispensable element for the formation of the membrane and its flexibility, and is a natural anti-inflammatory in the brain by balancing the presence of arachidonic acid, to reduce the possibility of degeneration of these important and delicate cells. Furthermore, the quantity of SATURATED FATS present in the membrane of neuronal cells must be balanced by that of unsaturated fats, otherwise the functioning of important proteins is inappropriate, as has been demonstrated for the sodium / potassium ATPase pump (PLoS One. 2013 Jun 19; 8 (6): e66418).

The observed imbalances establish a very important molecular information because, especially in the growth stages, as explained in Topic 1, there must be no anomalies in the composition of fats in cell membranes. Therefore, appropriate nutritional measures must be taken to bridge the imbalances and restore the membrane to its normal composition.

What is membrane lipidomic analysis? How can it help in autism?

The cell membrane can be “read” by analyzing its fat composition to understand if there are deficient elements that can cause it to malfunction (Expert Rev. Mol. Diagn. 2012, 12, 767–780; C. Ferreri, C. Chatgilialoglu, Membrane Lipidomics for Personalized Health, J. Wiley & Sons, Chichester, 2015). The method consists of isolating the mature red blood cell (taken from a small blood sample in EDTA as an anticoagulant), and obtaining its membrane with the extraction of fats, subsequently analyzed by gas chromatography (GC) which is the “gold standard” in this sector. The method is completely automated thanks to a robotics developed in the Lipidomics Laboratory of Lipinutragen, and the analysis is distributed under the name of FAT PROFILE®.

The lipidomic membrane analysis is a tool that first of all allows to understand if the subject is in a normal condition, without deficiencies in essential fats. Recall that the DEFICIENCY OF ESSENTIAL FATTY ACIDS (EFA deficiency) is well known in the books of Human Pathology and is linked to various neurological, metabolic, dermatological, immune, cardiovascular symptoms etc.

In addition, membrane lipidomic analysis allows fragile people, such as children already diagnosed for behavioral problems or attention deficit, to highlight and intervene on molecular deficiencies, which can contribute to the malfunction of the cells of the nervous system and their functions. Although the autistic spectrum is a complex pathological condition, not dating back to just one cause, it is important to avoid essential deficiencies in this type of patient who can contribute to the aggravation of already compromised functions. Recalling the importance of DHA as a neuro-anti-inflammatory element, it is highlighted that its absence makes it a fundamental defense of the nervous system. If inflammatory conditions occur without the protection of DHA, the nervous system at an early age would be more subjected to an insult and could not react effectively.

We are also convinced that, by highlighting these molecular deficiencies as soon as possible, for example in the immediately postnatal period, a sort of “molecular prevention” can be implemented by intervening on the body to fill the deficiency and allow the cells to reorganize their activities. This concerns above all those natural and spontaneous processes, such as the formation of cell membranes and the correct positioning of proteins in the membrane itself. These processes take place on the basis of what is present in the molecular kit of the cells. Providing for perfectly balanced kits is the first condition that allows the correct development of the organic tissue.

Considering all that has been said so far, it is very clear that lipidomic analysis is an indispensable tool for assessing normal levels of essential fatty acids and intervening on the highlighted deficits or imbalances, setting up a personalized nutra-strategy. This applies to prevention, before the diagnosis of disorders that could be traced back to a deficiency of essential fats, and also during the treatment of complex problems such as autism spectrum disorders. The clinical observation of the following months from the setting of a lipidomic strategy will tell which and how many improvements have been recorded, also making use of the control with a second lipidomic membrane analysis (after 4-6 months), to verify that essential fats intaked by the subject have reached their site of activity or: the CELL MEMBRANE.

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Article by
Dr. Carla Ferreri – First ISOF-CNR researcher and founding member Lipinutragen

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Photo: 123RF Archivio Fotografico: 98944691 ©Olga Yastremska /123rf.com

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Circadian diet

The evolutionary history of man testifies that we are a diurnal animal species. In fact, during the part of the day illuminated by sunlight, the main activities of research and consumption of food have always been carried out, and coherently with this our physiology has developed. In the night rest phase, biological investment functions predominate, aimed at repairing and regenerating organs and tissues such as those that occur in REM sleep.

Man has disconnected from the environment in which he lives gradually, up to the present day when, in western society, this link has been almost completely lost, together with the legacy of knowledge of traditional culture. This loss of connection with traditions also occurred in the way we feed ourselves: the quality of food (what), their quantity (how much) and the times of consumption of meals (when).

Chrono-Nutrition

As described in a previous article, there is an optimal window in which to feed and is regulated by a clock placed at the level of the central nervous system (central clock) synchronized with different peripheral clocks (slave clock), present both at the cellular level with gene expressions and organ with various functions. Some peripheral clocks have been identified at the level of the liver, pancreas, intestine, adipose and muscle tissue.

The first studies on the genetic link between circadian rhythms and metabolism concern the mutation of the ClockΔ19 / Δ19 gene on mouse models subjected to day –night rhythm dysregulation. The result of this study showed how this mutation led to the development in animals of arrhythmia, hyperphagia, hyperlipidemia with hepatic steatosis, dysglycemia due to insulin dysregulation (1).

The latest years, more and more scientific evidence has shown that circadian dysregulation of the sleep-wake rhythm and of the meal-fasting cycle lead to metabolic dysfunctions and an increased risk of disease, citing among others the Nurses’ Health Study (https://www.nurseshealthstudy.org/).

The coordination between the central clock and those in the peripheral organs occurs through nervous, endocrine, body temperature signals and behaviors such as the sleep-wake rhythm and meal times.

Thus, it appears that the pancreas also has its own biological clock which influences its secretion of insulin which, under physiological conditions and without food-induced stimulation, reaches a minimum in the hours of the night (2). In the night window, in fact, the presence of other hormones prevails, such as melatonin, GH, glucagon, etc. and immune and reparative processes.

How to predict how much post-prandial insulin remains in the circulation?

Foods’ insulin index (FII)

The foods’ insulin index (FII) is a recent parameter that indicates the increase in post-prandial insulin secretion compared to individual foods (3). The information provided by this parameter is very promising and integrates with that of the index and glycemic load because the latter are not always correlated with the insulin response. This occurs because in reality we do not eat individual macronutrients but we consume complex meals in which carbohydrates, proteins and fats are present.

Effect of lipids in the meal

Lipids for example, taken individually, do not particularly stimulate the release of insulin, while added to carbohydrates they increase the insulin response by up to 60% (4). It turns out that adding fats to meals also lengthens the insulinemic curve.

Studies done in the past have determined that the length of time insulin remains in the circulation after a mixed meal depends on the type of fat ingested, in particular on the length of their chain and on the number of double bonds present (5).

For non-professionals, the fats are made up of chains of carbon atoms, the number of which is indicated by the first digit, and the presence or absence of double bonds by the number after the colon.

From these premises it appears that those which have the greatest impact on the insulinemic curve are long-chain saturated fats, such as palmitic (C 16: 0) and stearic (C 18: 0) (Figure1).

The famous palmitic acid of palm oil is a C 16: 0, it has 16 carbon atoms and 0 double bonds. The oleic acid of the extra virgin olive oil is a C 18: 1, 18 carbon atoms and 1 double bond.

Follow a circadian diet

To set up a circadian diet it is important to provide for the maximum calorie intake in the early stages of the day; for example, 2/3 of the total calories between breakfast, lunch and various snacks and with light dinner, in terms of insulin demand.

The sequence of meals must also be modulated according to the different activities carried out (type of work, sport, etc.) and according to the obligatory dinner times. If it is not possible to bring forward the time of the last daily meal, it should be ensured that its load – in terms of calories and macronutrients – is inversely proportional to its time.

A low insulintropic effect is obtained with a mainly vegetable meal, with few proteins (mainly from vegetable or fish sources) and mono or polyunsaturated fats. Any starchy carbohydrates will be chosen from those with low glycemic impact also in order not to stimulate the endogenous formation of saturated fats.

To keep the insulinemic response of the evening meal to a minimum, it is necessary to reduce or exclude the sources of saturated fats present in fatty foods (cured meats, aged cheeses, mascarpone, etc.) or in added seasonings (butter).

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Bibliography:

(1) Marcheva B, et al. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinemia and diabetes. Nature. 2010; 466: 627-631.
(2) Vieira E., et al. Clock genes, pancreatic function, and diabetes. Trends Mol. Med. 20, 685–693 (2014).
(3) Bao J., et al. Food insulin index: physiologic basis for predicting insulin demand evoked by composite meals. Am J Clin Nutr 2009;90:986–92.
(4) Validation of the food insulin index in lean, young, healthy individuals, and type 2 diabetes in the context of mixed meals: an acute randomized crossover trial.
(5) McGarry J., et al. The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation. J Clin Invest. 1997 Jul 15; 100(2): 398–403

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Article by:

Francesco Bonucci – Nutritionist

The diet advise, written in the article, are not intended to be a substitute for a personal nutrition plan and should be adapted to specific cases

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Foto: 123RF Archivio Fotografico: 135057917 ©normaals /123rf.com

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The diet of modern society

Modern society, largely urbanized, is characterized by a strong sedentary lifestyle and by an ubiquitous presence of poor quality food, low in nutrients, inexpensive, but highly caloric. These characteristics make the western world highly obesogenic with all the health problems and chronic-degenerative diseases related to excess body fat.

Contrary, it is known that man has evolved in an environment with limited food resources and subject to cyclical periods of famine. Environmental pressure of this type made it possible to select the so-called saver genotype (thrifty gene hypothesis) which, in conditions of alternating presence of nutritional resources, is able to accumulate fats more easily. The stored depository fats, thanks to a greater insulin resistance, will then be used sparingly in times of famine. This phenotypic characteristic, successful over the centuries characterized by the non-constant presence of food resources, becomes instead a negative aspect for the modern society man. Food has become always available 24/7 all year round, without seasonal alternation exposing us to all dysmetabolic diseases such as obesity, hypertension and diabetes.

The negative effect of this, is current observed in populations that until a few decades ago lived in a traditional way and only recently have been “civilized” with Western food and the “cozy” and therefore sedentary lifestyle. This is the case of the Pima tribe, Native Americans of Arizona, who represent a living example of this transition of lifestyles with the consequent achievement of a very high levels of diabetes and obesity (up to over 75%) (2).

The energy balance model

With the aim of curbing the obesity, at the beginning of the 1900s the model based on the hypothesis of energy balance made its way, which sees the increase in body weight as an imbalance between incoming energy (the intake food) and consumed energy (basal metabolic rate + activity).

 

Figura 1: energy balance model.
(https://www.dgphysique.com/post/eating-clean-vs-being-in-a-calorie-deficit)

Calories introduced = calories consumed → weight maintenance
Calories introduced <calories consumed → weight loss
Calories introduced> calories consumed → weight gain[/vc_column_text][/vc_column_inner][/vc_row_inner]The model made its way in an era in which endocrinology had not yet developed and, in a very simplistic way, it equated the organism with an oven. Recall that in those times calorimeters were available and knowledge of the physiology of nutrition in its complexity as well as the metabolic axes that regulate energy expenditure were lacking. Not intending to refute the physics’ laws, it must in fact be considered that biological systems have homeostatic mechanisms that can alter the energy quotas dedicated to accumulation, rather than thermogenesis, or even the different degree of absorption or assimilation of nutrients, etc.

This calorie-centered model therefore appears limited and does not consider that the human body has an energy requirement below which it should not go down in order not to trigger defense mechanisms and energy savings typical of the saver phenotype.

Energy expenditure and consequences for the body

The total energy expenditure in the 24 hours (EE) is given by the Basal Metabolism (RMR) (sum of the expenditure of all organs and systems) + Thermal Effect of Food (TEF) (energy expenditure for the digestion of food and absorption) + Motor Activity, divided into Spontaneous (NEAT) and Voluntary (Exercise).

The following figure shows that the largest share of energy expenditure in 24 hours is given by the basal metabolism (Resting Metabolic Rate) which represents the cost, in terms of energy, of being alive and functioning. Digestion and assimilation of food depends very much on the type of food (consistency, presence of fibers, etc.) and on the metabolic conditions of the subject. Voluntary physical activity is on average a lower percentage than involuntary daily activities.

Figure 2:
percentages of energy expenditure by categories: Resting Metabolic Rate represents between 60-80% of the total, Thermic Effect of Meals / Food 10%, Physical activity (voluntary and otherwise) a very variable percentage between 20-50%.[/vc_column_text][/vc_column_inner][/vc_row_inner]Quite simply, if an individual with excess weight and body fat, introduces too many calories compared to his needs, it is obvious that eating less (and doing more exercises) represents an appropriate solution.

Contrary, for a person with excess body fat who eats less than his basal needs, perhaps with a past of drastic low-calorie diets, a reduction in energy intake can hardly be an effective strategy. An excessive calorie reduction, compared to individual needs, is interpreted by our neuroendocrine system as a stressor and will push the body to express the so-called saver phenotype, thus adapting to the calorie restriction without losing weight.

Lipids, from enemies to allies

Since fat is the highest energy macronutrient (about 9 kcal/g), the response to obesity based on the energy balance model has generated low-calorie diets with low fat content. In the 70s, the main nutritional guidelines established that the correct diet was the one with low fat and with the highest presence of carbohydrates. Based on this facts a whole industry of light and low fat products has developed, but with the presence of lots of sugars. It is clear to everyone that this model has been a failure and that diabetes and obesity (diabesity) has doubled several times in the past 40 years.

For this reason, dietary fats have been so reviled and only recently are they returning to the fore and acquiring a role of primary macronutrient and moving to a higher percentage (up to 35% of total calories) recommended by the guidelines for healthy nutrition (LARN IV edition, 2014).

Obviously not all fats are the same and must be intaken choosing between saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) omega 6 (ω-6) and omega 3 (ω-3), so it is a matter of balancing them by choosing the food sources properly.

Even at the molecular level we can observe that the cell is looking for a lipid balance in its plasma membrane. This is because fats have specific functions depending on the tissue or organ they are composing. In addition to the structural properties, lipids are among other things also signal molecules, fundamental in inflammatory and anti-inflammatory processes. Membrane fat imbalances can be correlated with different metabolic conditions, including obesity.

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Bibliography:

1. Neel JV. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? 1962. Am J Hum Genet.
2. Schulz LO. Effects of Traditional and Western Environments on Prevalence of Type 2 Diabetes in Pima Indians in Mexico and the U.S. 2006. Diabetes Care.
3. Manini TM. Energy expenditure and aging. 2010. Ageing Research Review

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Article by:

Francesco Bonucci – Nutrizionista

The diet advise, written in the article, are not intended to be a substitute for a personal nutrition plan and should be adapted to specific cases

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Photo: 123RF Archivio Fotografico: 27291006 ©Natalia Klenova /123rf.com

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