Glycogen: definition, structure and functions

What is glycogen?

Glycogen Structure
Fig. 1 – Glycogen Structure

Glycogen is an homopolysaccharide formed by units of glucose. Chemically similar to amylopectin, and therefore sometimes referred to as animal starch, compared to the latter it is more compact, extensively branched and larger, reaching a molecular weight up to 108 Da corresponding to about 600000 glucose molecules.
As in the amylopectin, glucose units in the main chain and in the lateral chains are linked by α-(1→4) glycosidic bonds. Lateral chains are joined to the main chain by an α-(1→6) glycosidic bond; unlike amylopectin branches are more frequent, approximately every 10 glucose units (rather than every 25-30 as in amylopectin) and are formed by a smaller numbers of glucose units.
Glycogen is located in the cytosol of the cell in the form of hydrated granules of diameter between 1 to 4 µm and forms complexes with regulatory proteins and enzymes responsible for its synthesis and degradation.

Functions of glycogen

Glycogen, discovered in 1857 by French physiologist Claude Bernard, is the storage form of glucose, and therefore of energy, in animals in which it is present in the liver, muscle (skeletal and heart muscle) and in lower amounts in nearly all the other tissues and organs.
In humans it represents less than 1% of the body’s caloric stores (the other form of caloric reserve, much more abundant, is triacylglycerols stored in adipose tissue) and is essential for maintaining normal glycemia too.
It represents about 10% of liver weight and 1% of muscle weight; although it is present in a higher concentration in the liver, the total stores in muscle are much higher thanks to its greater mass (in a non-fasting 70 kg adult male there are about 100 g of glycogen in the liver and 250 g in the muscle).

  • Liver glycogen stores is a glucose reserve that hepatocyte releases when needed to maintain a normal blood sugar levels: if you consider glucose availability (in a non-fasting 70 kg adult male) there is about 10 grams or 40 kcal in body fluids while hepatic glycogen can supply, also after a fasting night, about 600 kcal.
  • In skeletal and cardiac muscle, glucose from glycogen stores remains within the cell and is used as an energy source for muscle work.
  • The brain contains a small amount of glycogen, primarily in astrocytes. It accumulates during sleep and is mobilized upon waking, therefore suggesting its functional role in the conscious brain. These glycogen reserves also provide a moderate degree of protection against hypoglycemia.
  • It has a specialized role in fetal lung type II pulmonary cells. At about 26 weeks of gestation these cells start to accumulate glycogen and then to synthesize pulmonary surfactant, using it as a major substrate for the synthesis of surfactant lipids, of which dipalmitoylphosphatidylcholine is the major component.
Glycogen: Dipalmitoylphosphatidylcholine
Fig. 1 – Dipalmitoylphosphatidylcholine

Glycogen and foods

It is absent from almost all foods because after an animal is killed it is rapidly broken down to glucose and then to lactic acid; it should be noted that the acidity consequently to lactic acid production gradually improves the texture and keeping qualities of the meat. The only dietary sources are oysters and other shellfish that are eaten virtually alive: they contain about 5% glycogen.

In humans, accumulation of glycogen is associated with weight gain due to water retention: for each gram of stored glycogen 3 grams of water are retained.

References

Arienti G. “Le basi molecolari della nutrizione”. Seconda edizione. Piccin, 2003

Cozzani I. and Dainese E. “Biochimica degli alimenti e della nutrizione”. Piccin Editore, 2006

Giampietro M. “L’alimentazione per l’esercizio fisico e lo sport”. Il Pensiero Scientifico Editore, 2005

Mahan LK, Escott-Stump S.: “Krause’s foods, nutrition, and diet therapy” 10th ed. 2000

Mariani Costantini A., Cannella C., Tomassi G. “Fondamenti di nutrizione umana”. 1th ed. Il Pensiero Scientifico Editore, 1999

Nelson D.L., M. M. Cox M.M. Lehninger. Principles of biochemistry. 4th Edition. W.H. Freeman and Company, 2004

Stipanuk M.H.. “Biochemical and physiological aspects of human nutrition” W.B. Saunders Company-An imprint of Elsevier Science, 2000

Adherence to the Mediterranean Diet, cognitive status and cognitive decline in women

Adherence to the Mediterranean Diet and cognitive status in women
Adherence to the Mediterranean Diet: Cognitive status in women

In a large-scale prospective epidemiological study published on Journal of Nutrition a research team examined associations of long-term adherence to the Mediterranean Diet (adherence was based on intakes of: vegetables, legumes, fruits, nuts, whole grains, fish, red and processed meats, moderate alcohol, and the ratio of monounsaturated:saturated fat) and subsequent cognitive function and its decline.
The participants, 16,058 women from the Nurses’ Health Study, aged ≥70 y, underwent cognitive testing 4 times during 6 y.
The study showed that long-term Mediterranean Diet adherence was related to moderately better cognition but not with cognitive decline in this very large cohort of older women.

Samieri C., Okereke O.I., E. Devore E.E. and Grodstein F. Long-Term adherence to the Mediterranean Diet is associated with overall cognitive status, but not cognitive decline, in women. J Nutr 2013;143:493-9

How to reduce body fat

How to reduce body fat: contents in brief

Body fat and daily caloric balance

The international scientific literature is unanimous in setting the lower limit for the daily caloric intake to 1200 kcal for women and 1500 kcal for men (adults).

Body Fat
Fig. 1 – Daily Caloric Balance

To make negative the daily caloric intake, and therefore lose body weight, but expecially lose body fat, evaluation of actual caloric needs of the subject will be alongside:

  • the correct distribution of meals during the day;
  • an increased physical activity, by which the negative balance can be achieved without major sacrifices during meals.

This will make weight loss easier and protect from subsequent weight gains (body fat).
Ultimately, there must be a change in lifestyle.

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Lose body fat and “miracle diets”

So, the best strategy for losing body fat is not a drastic reduction in caloric intake, nor follow constrictive or “strange” diets, such as hcg diet plan, sacred heart diet, paleo diet, Master Cleanse diet (the diet that Beyonce did), etc., that require to eliminate or greatly reduce the intake of certain macronutrients, mostly carbohydrates.
Such conducts can be:

  • very stressful from psychological point of view;
  • not passable for long periods;
  • hazardous to health because of inevitable nutrient deficiencies.

Finally, they do not ensure that all the weight lost is only or almost only body fat and are often followed by substantial increases in body weight (weight cycling or yo-yo effect).
Why?

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Body fat and excessive reduction of energy intake

An excessive reduction of energy intake means eating very little and this determines the risk, high, not to take adequate amounts of the various essential nutrients, that is, what we can’t synthesize, such as vitamins, certain amino acids, some fatty acids and minerals, including e.g. calcium, essential for bone metabolism at every stage of life, or iron, used in many body functions as the transport of oxygen to the tissues. This results in a depression of metabolism and hence a reduction in energy expenditure.
Whether the reduction in energy intake is excessive, or even there are periods of fasting, it adds insult to injury because a proportion of free fatty mass will be lost. How?

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Body fat, reduction in energy intake and role of carbohydrates

Glucose is the only energy source for red blood cells and some brain areas, while other brain areas can also derive energy from ketone bodies, which are a product of fatty acid metabolism.
At rest, brain extracts 10% of the glucose from the bloodstream, a significant amount, about 75 mg/min., considering that its weight is about 1.5 kg. To maintain a constant glycemia, and thus ensure a constant supply of glucose to tissues, we needs to take carbohydrates or alternatively amino acids, both easily obtained from foods.
In the case of a low or absent dietary intake of carbohydrates, whereas after about 18 hours liver glycogen, which releases glucose into circulation, depletes, body synthesizes de novo glucose from certain amino acids through a process called gluconeogenesis (actually this metabolic pathway is active even after a normal meal but increases its importance in fasting).
But what’s the main source of amino acids in the body when their dietary intake is low or absent? Endogenous proteins, and there is a hierarchy in their use that is before we consume the less important and only after the most important ones. For the first digestive enzymes, pepsin, chymotrypsin, elastase, carboxypeptidase and aminopeptidase (around 35-40 g) will be used; successively liver and pancreas slow down their synthesis activities for export proteins and unused amino acids are directed to gluconeogenesis. It’s clear that these are quite modest reserves of amino acids and it is the muscle that will undertake to provide the required amounts of amino acids that is proteolysis of muscle proteins begins.
Note: Anyway, there is no absolute sequentiality in the degradation of several proteins, there is instead a plot in which, proceeding, some ways lose their importance and others will buy. So, to maintain constant glycemia the protein component of muscle is reduced, including skeletal muscle that is a tissue that represents a fairly good portion of the value of the basal metabolism and that, with exercise, can significantly increase its energy consumption: thus essential for weight loss and subsequent maintenance. It is as if the engine capacity was reduced.
One thing which we don’t think about is that heart is a muscle that may be subject to the same processes seen for skeletal muscle.
Ultimately make glucose from proteins, also food-borne, is like heat up the fire-place burning the furniture of the eighteenth century, amino acids, having available firewood, dietary carbohydrates.
Therefore, an adequate intake of carbohydrates with diet prevents excessive loss of proteins, namely, there is a saving effect of proteins played by carbohydrates.
Mammals, and therefore humans, can’t synthesize glucose from fats.

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What goes in when carbohydrates goes out?

The elimination or substantial reduction in carbohydrate intake in the diet results in an increased intake of proteins, fats and cholesterol because it will increase the intake of animal products, one of the main defects in hyperproteic diet.
In the body there are no amino acids reserves, thus they are metabolized and, as a byproduct of their use, ammonia is formed and it’ll be eliminated as toxic. For this reason high-protein diets imply an extra work for liver and kidneys and also for this they are not without potential health risks.
An increased fat intake often results into an increased intake of saturated and trans fats and cholesterol, with all the consequences this may have on cardiovascular health.
What has been said so far should not induce to take large amounts of carbohydrates; this class of macronutrients should represent 55-60% of daily calories, fats 25-30% (primarily extra-virgin olive oil) and the remainder proteins: thus a composition in macronutrient that refers to prudent diet or Mediterranean Diet.

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Body fat and the entry in a phase of famine/disease

A excessive reduction in caloric intake is registered by our defense mechanisms as an “entry” in a phase of famine/disease.
The abundance of food is a feature of our time, at least in industrialized countries, while our body evolved over hundreds of thousands of years during which there was no current abundance: so it’s been programmed to try to overcome with minimal damage periods of famine. If caloric intake is drastically reduced it mimics a famine: what body does is to lower consumption, lower the basal metabolism, that is, consumes less and therefore also not eating much we will not get great results. It is as if a machine is lowered the displacement, it’ll consume less (our body burns less body fat).

In summary, the best way to lose body fat, that also protects against future increases, is to make negative the daily caloric balance increasing physical activity and controlling food intake, i.e. change your own lifestyle.

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References

Cereda E., Malavazos A.E., Caccialanza R., Rondanelli M., Fatati G. and Barichella M. Weight cycling is associated with body weight excess and abdominal fat accumulation: a cross-sectional study. Clin Nutr 2011;30(6):718-23. doi:https://doi.org/10.1016/j.clnu.2011.06.009

Giampietro M. L’alimentazione per l’esercizio fisico e lo sport. Il Pensiero Scientifico Editore. Prima edizione 2005

Ravussin E., Lillioja S., Knowler W.C., Christin L., Freymond D., Abbott W.G.H., Boyce V., Howard B.V., and Bogardus C. Reduced rate of energy expenditure as a risk factor for body-weight gain. N Engl J Med 1988;318:467-72.doi:10.1056/NEJM198802253180802

Sachiko T. St. Jeor S.T. St., Howard B.V., Prewitt T.E., Bovee V., Bazzarre T., Eckel T.H., for the AHA Nutrition Committee. Dietary Protein and Weight Reduction. A Statement for Healthcare Professionals From the Nutrition Committee of the Council on Nutrition, Physical Activity, and Metabolism of the American Heart Association. Circulation 2001;104:1869-74. doi:https://doi.org/10.1161/hc4001.096152

Primary prevention of cardiovascular disease and Mediterranean Diet

Mediterranean diet and primary prevention of cardiovascular disease

Primary prevention: Walnuts and extra-virgin olive oil: healthy fats
Fig. 1 – Walnuts and extra-virgin olive oil: healthy fats

A Spanish research team conducted a multicenter randomized trial of Mediterranean Diet pattern for the primary prevention of cardiovascular events.
The participants (7447; age range 55 to 80 years; 57% women) were with no cardiovascular disease but at high cardiovascular risk at enrollment (they had either type 2 diabetes mellitus or at least three of the following major risk factors: hypertension, smoking, overweight or obesity, elevated low-density lipoprotein cholesterol levels, low high-density lipoprotein cholesterol levels or a family history of premature coronary heart disease).
They were randomly assigned to one of three diets:

  • a Mediterranean Diet supplemented with mixed nuts (30 g of mixed nuts: 7.5 g of almonds, 7.5 g of hazelnuts and 15 g of walnuts);
  • a Mediterranean Diet supplemented with extra-virgin olive oil (≥4 tbsp/day);
  • a control diet (advice to reduce dietary fat).

It should be noted that extravirgin olive oil is the cornerstone of Mediterranean Diet.

Moreover, in comparison with those in the control group, participants in the two Mediterranean-Diet groups significantly increased weekly servings of legumes and fish. These were the only between-group differences.
No physical activity was promoted, nor total calorie restriction advised.
Participants were followed for a median of 4.8 years.
The primary end point was the rate of myocardial infarction, stroke, or death from cardiovascular causes that is the rate of major cardiovascular events.

This study have shown that among persons at high cardiovascular risk, a Mediterranean Diet supplemented with nuts or extra-virgin olive oil has proved to be effective in the primary prevention of cardiovascular disease, reducing the incidence of major cardiovascular events.

Estruch R., Ros E., Salas-Salvadó J., et al. Primary prevention of cardiovascular disease with a Mediterranean Diet. N Engl J Med 2013

Long chain fatty acid synthesis

Fatty acid synthesis: contents in brief

Fatty acid synthesis

Fatty Acid Synthesis
Fig. 1 – Long Chain Fatty Acids

When excess calories are consumed from carbohydrates or proteins, such surplus is used to synthesize fatty acids and then triacylglycerols, while it doesn’t occur if the excess come from fats.

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De novo fatty acid synthesis in plants and animals

De novo fatty acid synthesis is largely similar among plants and animals.
It occurs in chloroplasts of photosynthetic cells of higher plants, and in cytosol of animal cells by the concerted action of two enzymes: acetyl-CoA carboxylase (EC 6.4.1.2) and fatty acid synthase (EC 2.3.1.85).
Fatty acid synthase is a multienzyme complex that catalyzes a repeating four-step sequence by which the fatty acyl chain is extended by two carbons, at the carboxyl end, every each passage through the cycle; this four-step process is the same in all organisms.
In animals, the primary site for lipid metabolism is liver, not the adipose tissue.  However, adipose tissue is  a major organ system in which fatty acid synthesis occurs, though in humans it is less active than in many other animal species.

Fatty Acid Synthesis
Fig. 2 – Palmitic Acid Synthesis

Although myristic, lauric and a trace of stearic acids may also be produced, in animals and plants the main product of these reactions is palmitic acid.
It should be noted that in certain plants, such as palm and coconut, chain termination occurs earlier than palmitic acid release: up to 90% of the fatty acids produced and then present in the oils of these plants are between 8 (caprylic acid) and 14 (myristic acid) carbons long (palmitic acid: 16 carbon atoms).

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Synthesis of long chain saturated and unsaturated fatty acids

Fatty Acid Synthesis
Fig. 3 – Palmitic Acid Metabolism

Palmitic acid is the commonest saturated fatty acid in plant and animal lipids, but generally it is not present in very large proportions because it may be undergo into several metabolic pathways.
In fact:

  • it is the precursor of stearic acid;
  • it may be desaturated (insertion of a double bond into fatty acid chain) to palmitoleic acid, the precursor of all fatty acids of omega-7 or n-7 family, in a reaction catalyzed by Δ9-desaturase (EC 1.14.19.1), an ubiquitous enzyme in both plant and animal kingdoms and the most active lipid enzyme in mammalian tissues, the same enzyme that catalyzes the desaturation of stearic acid to oleic acid (see below).
    Note: Δ9- desaturase inserts double bounds in the 9-10 position of the fatty acid carbon chain, position numbered from the carboxyl end of the molecule, and:

if the substrate is palmitic acid, the double bond will appear between n-7 and n-8 position of the chain (in this case numbered from the methyl end of the molecule), so producing palmitoleic acid, the founder of omega-7 series;
numbering-atoms-palmitic-acid

if the substrate is stearic acid, the double bond will appear between n-9 and n-10 position of the chain and oleic acid will be produced.
numbering-atoms-stearic-acid

  • It may be esterified into complex lipids.

Of course, in plants and animals there are fatty acids longer and/or more unsaturated than these just seen thanks to modification systems (again desaturation and elongation) that catalyze reactions of fatty acid synthesis that are organism- tissue- and cell- specific.

Fatty Acid Synthesis
Fig. 4 – Stearic Acid Metabolism

For example, stearic acid may be:

  • elongated to arachidic, behenic and lignoceric acids, all saturated fatty acids, in reactions catalyzed by elongases. Again, chain elongation occurs, both in mitochondria and in the smooth endoplasmic reticulum, by the addition of two carbon atom units at a time at the carboxylic end of the fatty acid through the action of fatty acid elongation systems (particularly long and very long saturated fatty acids, from 18 to 24 carbon atoms, are synthesized only on cytosolic face of the smooth endoplasmic reticulum);
  • desaturated, as seen, to oleic acid, an omega-9 or n-9 fatty acid, in a reaction catalyzed by Δ9-desaturase.
    Several researchers have postulated that the reason for which stearic acid is not hypercholesterolemic is its rapid conversion to oleic acid.
Fatty Acid Synthesis
Fig. 5 – Oleic Acid Metabolism

Oleic acid is the start point for the synthesis of many other unsaturated fatty acids by reactions of elongation and/or desaturation.

In fact:

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Omega-3 and omega-6 PUFA synthesis

Fatty Acid Synthesis
Fig. 6 – Omega-3 and Omega-6 Synthesis

Animal tissues can desaturate fatty acids in the 9-10 position of the chain, thanks to the presence of Δ9 desaturase; as previously seen, if the substrate of the reaction is palmitic acid, the double bond will appear between n-7 and n-8 position, with stearic acid between n-9 and n-10 position, so leading to formation respectively of palmitoleic acid and oleic acid.
Animals lack Δ12- and Δ15-desaturases, enzymes able to desaturate carbon carbon bonds beyond the 9-10 position of the chain. For these reason, they can’t produce de novo omega-3 and omega-6 PUFA (which have double bonds also beyond the 9-10 position), that are so essential fatty acids.
Δ12- and Δ15-desaturases are present in plants; though many land plants lack Δ15-desaturase, also called omega-3 desaturase, planktons and aquatic plants in colder water possess it and produce abundant amounts of the omega-3 fatty acids.

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References

Akoh C.C. and Min D.B. “Food lipids: chemistry, nutrition, and biotechnology”. CRC Press Taylor & Francis Group, 2008 3th ed. 2008

Bender D.A. “Benders’ dictionary of nutrition and food technology”. 2006, 8th Edition. Woodhead Publishing. Oxford

Burr G. and Burr M. A new deficiency disease produced by the rigid exclusion of fat from the diet. J Biol Chem 1929;82:345-67 [Full Text]

Chow Ching K. “Fatty acids in foods and their health implication”. 3rd Edition. CRC Press Taylor & Francis Group, 2008

Cozzani I. e Dainese E. “Biochimica degli alimenti e della nutrizione”. Piccin Editore, 2006

Rosenthal M.D., Glew R.H. Mediacal biochemistry. Human metabolism in health and disease. John Wiley & Sons, Inc. 2009

Stipanuk M.H.. Biochemical and physiological aspects of human nutrition. W.B. Saunders Company-An imprint of Elsevier Science, 2000

Strategies to maximize muscle glycogen resynthesis after exercise

Strategies to maximize muscle glycogen resynthesis after exercise: contents in brief

Post-exercise muscle glycogen synthesis

An important energy source for working muscle is its glycogen store, whose level is correlated with the onset of fatigue.
The highly trained athlete not only has glycogen stores potentially higher but he is also able to synthesize it faster thanks to more efficient enzymes.
To synthesize glycogen it is necessary to ingest carbohydrates; but how many, which, when, and how often?

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The two phases of muscle glycogen synthesis after exercise

In order to restore as quickly as possible muscle glycogen depots, it is useful to know that, as a result of training sessions that deplete muscle glycogen to values below 75% those at rest and not fasting, glycogen synthesis occurs in two phases.
To know and therefore take advantage of the biphasicity is important for those athletes who are engaged in more daily training sessions, or who otherwise have little time for recovery between a high intensity exercise and the subsequent one (less than 8 hours), in order to maximize glycogen synthesis and achieve the optimal performance during a second close exercise session.
The two phases are characterized by:

  • a different sensitivity to circulating insulin levels;
  • a different velocity.

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Muscle glycogen synthesis after exercise: the first phase

Muscle Glycogen
Fig. 1 – Glycogen Structure

The first phase, immediately following the end of an activity and lasting 30-60 minutes, is insulin-independent, i.e. glucose uptake by muscle cell as glycogen synthesis are independent from hormone action.
This phase is characterized by an elevated rate of synthesis that however decreases rapidly if you do not take in carbohydrates: the maximum rate is in the first 30 minutes, then declines to about one fifth in 60 minutes, and to about one ninth in 120 minutes from the end of exercise.
How is it possible to take advantage of this first phase to replenish muscle glycogen stores as much as possible? By making sure that the greatest possible amount of glucose arrives to muscle in the phase immediately following to the end of exercise, best if done within the first 30 minutes.

  • What to ingest?
    High glycemic index, but easy to digest and absorb, carbohydrates.
    Therefore, it is advisable to replace foods, even though of high glycemic index, that need some time for digestion and the subsequent absorption, with solutions/gel containing for example glucose and/or sucrose. These solutions ensure the maximal possible absorption rate and resupply of glucose to muscle because of they contain only glucose and are without fiber or anything else that could slow their digestion and the following absorption of the monosaccharide, that is, they are capable of producing high blood glucose levels in a relatively short time.
    It is also possible to play on temperature and concentration of the solution to accelerate the gastric transit.
    It should be further underlined that the use of these carbohydrate solutions is recommended only when the recovery time from a training/competition session causing significant depletion of muscle glycogen and the following one is short, less than 8 hours.
  • How many carbohydrates do you need?
    Many studies has been conducted to find the ideal amount of carbohydrates to ingest.
    If in post-exercise the athlete does not eat, glycogen synthesis rate is very low, while if he ingests adequate amounts of carbohydrates immediately after cessation of exercise, synthesis rate can reach a value over 20 times higher.
    From the analysis of scientific literature it seems reasonable to state that, as a result of training sessions that deplete muscle glycogen stores as seen above (<75% of those at rest and not fasting), the maximum synthesis rate is obtained by carbohydrate intake, with high glycemic index and high digestion and absorption rates, equal to about 1.2 g/kg of body weight/h for the next 4-5 hours from the end of exercise.
    In this way, the amount of glycogen produced is higher than 150% compared to the ingestion of 0.8 g/kg/h.
    Because further increases, up to 1.6 g/kg/h, do not lead to further rise in glycogen synthesis rate, the carbohydrate amount equal to 1.2 g/kg/h can be considered optimum to maximize the resynthesis rate of muscle glycogen stores during post-exercise.
  • And the frequency of carbohydrate ingestion?
    It was observed that if carbohydrates are ingested frequently, every 15-30 minutes, it seems there is a further stimulation of muscle glucose uptake as of muscle glycogen replenishment compared with ingestion at 2-hours intervals. Particularly, ingestions in the first post-exercise hours seem to optimize glycogen levels.

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Muscle glycogen synthesis after exercise: the second phase

The second phase begins from the end of the first, lasts until the start of the last meal before the next exercise (hence, from several hours to days), and is insulin-dependent i.e. muscle glucose uptake and glycogen synthesis are sensitive to circulating hormone levels.
Moreover, you observe a significant reduction in muscle glycogen synthesis rate: with adequate carbohydrate intake the synthesis rate is at a value of about 10-30% lower than that observed during the first phase.
This phase can last for several hours, but tends to be shorter if:

In order to optimize the resynthesis rate of glycogen, experimental data indicate that meals with high glycemic index carbohydrates are more effective than those with low glycemic index carbohydrates; but if between a training/competition session and the subsequent one days and not hours spend, the evidences do not favor high glycemic index carbohydrates as compared to low glycemic index ones as long as an adequate amount is taken in.

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Muscle glycogen synthesis rate and ingestion of carbohydrates and proteins

The combined ingestion of carbohydrates and proteins (or free insulinotropic amino acids) allows to obtain post-exercise glycogen synthesis rate that does not significantly differ from that obtained with larger amounts of carbohydrates alone. This could be an advantage for the athlete who may ingest smaller amount of carbohydrates, therefore reducing possible gastrointestinal complications commons during training/competition afterward to their great consumption.
From the analysis of scientific literature it seems reasonable to affirm that, after an exercise that depletes at least 75% of muscle glycogen stores, you can obtain a glycogen synthesis rate similar to that reached with 1.2 g/kg/h of carbohydrates alone (the maximum obtainable) with the coingestion of 0.8 g/kg/h of carbohydrates and 0.4 g/kg /h of proteins, maintaining the same frequency of ingestion, therefore every 15-30 minutes during the first 4-5 hours of post-exercise.

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The two phases of muscle glycogen synthesis: molecular mechanisms

The biphasicity is consequence, in both phases, of an increase in:

  • glucose transport rate into cell;
  • the activity of glycogen synthase, the enzyme that catalyzes glycogen synthesis.

However, the molecular mechanisms underlying these changes are different.
In the first phase, the increase in glucose transport rate, independent from insulin presence, is mediated by the translocation, induced by the contraction, of glucose transporters, called GLUT4, on the cytoplasmatic membrane of the muscle cell.
In addition, the low glycogen levels also stimulate glucose transport as it is believed that a large portion of transporter-containing vesicles are bound to glycogen, and therefore they may become available when its levels are depleted.
Finally, the low muscle glycogen levels stimulate glycogen synthase activity too: it has been demonstrated that these levels are a regulator of enzyme activity far more potent than insulin.
In the second phase, the increase in muscle glycogen synthesis is due to insulin action on glucose transporters and on glycogen synthase activity of muscle cell. This sensibility to the action of circulating insulin, that can persist up to 48 hours, depending on carbohydrate intake and the amount of resynthesized muscle glycogen, has attracted much attention: it is in fact possible, through appropriate nutritional intervention, to increase the secretion in order to improve glycogen synthesis itself, but also protein anabolism, reducing at the same time the protein-breakdown rate.

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Glycogen synthesis rate and insulin

The coingestion of carbohydrates and proteins (or free amino acids) increases postprandial insulin secretion compared to carbohydrates alone (in some studies there was an increase in hormone secretion 2-3 times higher compared to carbohydrates alone).
It was speculated that, thanks to the higher circulating insulin concentrations, further increases in post-exercise glycogen synthesis rate could be obtained compared to those observed with carbohydrates alone, but in reality it does not seem so. In fact, if carbohydrate intake is increased to 1.2 g/kg/h plus 0.4 g/kg/h of proteins no further increases in glycogen synthesis rate are observed if compared to those obtained with the ingestion of carbohydrates alone in the same amount (1,2 g/kg/h, that, as mentioned above, like the coingestion of 0,8 g/kg/h of carbohydrates and 0,4 g/kg/h of proteins, allows to attain the maximum achievable rate in post-exercise) or in isoenergetic quantities, that is, 1.6 g/kg (proteins and carbohydrates contain the same calorie/g)

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Insulin and preferential carbohydrate storage

The greater circulating insulin levels reached with the coingestion of carbohydrates and proteins (or free amino acids) might stimulate the accumulation of ingested carbohydrates in tissues most sensitive to its action, such as liver and previously worked muscle, thus resulting in a more efficient storage, for the purposes of sport activity, of the same carbohydrates.

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References

Beelen M., Burke L.M., Gibala M.J., van Loon J.C. Nutritional strategies to promote postexercise recovery. Int J Sport Nutr Exerc Metab 2010:20(6);515-32 doi:10.1123/ijsnem.20.6.515

Berardi J.M., Noreen E.E., Lemon P.W.R. Recovery from a cycling time trial is enhanced with carbohydrate-protein supplementation vs. isoenergetic carbohydrate supplementation. J Intern Soc Sports Nutrition 2008;5:24 doi:10.1186/1550-2783-5-24

Betts J., Williams C., Duffy K., Gunner F. The influence of carbohydrate and protein ingestion during recovery from prolonged exercise on subsequent endurance performance. J Sports Sciences 2007;25(13):1449-60 doi:10.1080/02640410701213459

Howarth K.R., Moreau N.A., Phillips S.M., and Gibala M.J. Coingestion of protein with carbohydrate during recovery from endurance exercise stimulates skeletal muscle protein synthesis in humans. J Appl Physiol 2009:106;1394–1402 doi:10.1152/japplphysiol.90333.2008

Jentjens R., Jeukendrup A. E. Determinants of post-exercise glycogen synthesis during short-term recovery. Sports Medicine 2003:33(2);117-144 doi:10.2165/00007256-200333020-00004

Millard-Stafford M., Childers W.L., Conger S.A., Kampfer A.J., Rahnert J.A. Recovery nutrition: timing and composition after endurance exercise. Curr Sports Med Rep 2008;7(4):193-201 doi:10.1249/JSR.0b013e31817fc0fd

Price T.B., Rothman D.L., Taylor R., Avison M.J., Shulman G.I., Shulman R.G. Human muscle glycogen resynthesis after exercise: insulin-dependent and –independent phases. J App Physiol 1994:76(1);104–111 doi:10.1152/jappl.1994.76.1.104

van Loon L.J.C., Saris W.H.M., Kruijshoop M., Wagenmakers A.J.M. Maximizing postexercise muscle glycogen synthesis: carbohydrate supplementation and the application of amino acid or protein hydrolysate mixtures. Am J Clin Nutr 2000;72: 106-111 doi:10.1093/ajcn/72.1.106

Skeletal muscle glycogen stores and sports

Functions of skeletal muscle glycogen

Muscle glycogen represents a source of glucose, therefore energy, that can be used by muscle during physical activity: it is an energy store where needed!
Furthermore a close relationship exists between the onset of fatigue and depletion of its muscle stores.

Glycogen as energy source

Carbohydrates and fatty acids represent the main energy source for muscle during exercise and their relative contribution varies depending on:

  • the intensity and duration of exercise;
  • the level of training.

If for fatty acids there are no problems regarding body stores so it is not for carbohydrates whose stores, present in glycogen form principally in the liver and the muscle, are modest, less than 5% of total body energy stores: in a non-fasting 70 kg adult male there are about 250 g of glycogen in the muscle and 100 g in the liver, for a total energy of about 1400 kcal. In athletes the amount could be higher, for example in the best marathoners, again considering an adult male as above, you can reach up to 475 g in total, muscle plus liver, which corresponds to about 1900 kcal.
In spite of this, glycogen contribution to the total energy needed to sustain muscular workload rises with the increase of exercise intensity, whereas we reduce that in the form of fatty acids.
Furthermore, in the absence of replenishment with exogenous carbohydrates, performance is determined by the endogenous stores of liver and skeletal muscle glycogen, of which relative consumption is different: an increase of intensity increases that of the second (muscle) while remain more or less constant in that of the first (liver).

Skeletal muscle glycogen and intese exercises

In fact, skeletal muscle glycogen represents the most important energy reserve for prolonged moderate-high intensity exercise, an importance that increase in the case of high-intensity interval exercise (common in training session undertaken by swimmers runners, rowers or in team-sport players) or in resistance exercise, therefore both endurance and resistance exercises. If for example we consider the marathon about 80% of utilized energy derives from carbohydrate oxidation, for the most part skeletal muscle glycogen.
Finally, the replenishment rate of glycogen stores in post-exercise is one of the most important factors in establishing necessary recovery time.

Muscle glycogen and fatigue

Fatigue and low glycogen levels are closely correlate but it is not clear which mechanisms are at the basis of this relationship; one hypothesis is that there exists a minimum glycogen concentration that is “protected” and is resistant to being used during exercise, perhaps to ensure an energy reserve in case of extreme necessity.
Because of the closely relationship between skeletal muscle glycogen depletion and fatigue, its replenish rate in the post-exercise is one of the most important factors in determining necessary recovery time.

References

Arienti G. “Le basi molecolari della nutrizione”. Seconda edizione. Piccin, 2003

Beelen M., Burke L.M., Gibala M.J., van Loon J.C. Nutritional strategies to promote postexercise recovery. Int J Sport Nutr Exerc Metab 2010:20(6);515-32 doi:10.1123/ijsnem.20.6.515

Cozzani I. and Dainese E. “Biochimica degli alimenti e della nutrizione”. Piccin Editore, 2006

Giampietro M. “L’alimentazione per l’esercizio fisico e lo sport”. Il Pensiero Scientifico Editore, 2005

Mahan LK, Escott-Stump S.: “Krause’s foods, nutrition, and diet therapy” 10th ed. 2000

Mariani Costantini A., Cannella C., Tomassi G. “Fondamenti di nutrizione umana”. 1th ed. Il Pensiero Scientifico Editore, 1999

Nelson D.L., M. M. Cox M.M. Lehninger. Principles of biochemistry. 4th Edition. W.H. Freeman and Company, 2004

Stipanuk M.H.. “Biochemical and physiological aspects of human nutrition” W.B. Saunders Company-An imprint of Elsevier Science, 2000

Christmas holidays, a danger for our figures?

If the situation eludes our control it is possible, indeed probable!
Only a few stubborn people will be able to lose weight in this period; instead for “all of us” a good result will be “damage limitation” and we succeed in doing so only if we will not fill our homes to the brim with dainties which we can’t resist (we are putting enemies in our home!); Pandori, Panettone, chocolate, dried fruit, cured meats etc. etc. that will put us through the mill for weeks and weeks and in the end they’ll win……

Except Christmas Eve and Christmas dinner, however, where it is not advisable to exceed, in the remaining holidays we should attempt to eat as healthy as possible meanwhile keeping a good level of physical activity.

In fact it is good practice to remember that we don’t increase our weight from Christmas day to St. Stephen’s day but from St. Stephen’s Day to Christmas day.

Happy Christmas to you all!

 

Daily protein requirements for athletes

Daily protein requirements and sports

Proteins Requirements
Fig. 1 – Food High in Proteins

It is now accepted by athletes, coaches and athletic trainers that proper diet is one of the cornerstones for achieving better athletic performance. Despite this widely spread assumption, many, even at the highest levels, still believe that an high protein intake is fundamental in the athlete’s diet. This opinion is not new and is deeply rooted in the imaginary of many people almost as if, eating meat, even of big and strong animals, we were able to gain their strength and vitality too.
The function of proteins as energy-supplier for working muscle was hypothesized for the first time by von Liebig in ‘800 and it is because of his studies if, even today, animal proteins, and therefore meats, are often believed having great importance in the energy balance in the athlete’s diet, despite nearly two centuries in which biochemistry and sports medicine have made enormous progress.
Really, by the end of ‘800 von Pettenkofer and Voit and, at the beginning of ‘900, Christensen and Hansen retrenched their importance for energy purposes, also for the muscle engaged  in sport performance, instead bringing out the prominent role played by carbohydrates and lipids.
Of course we shouldn’t think that proteins are not useful for the athlete or sedentary people. The question we need to answer is how many proteins a competitive athlete, engaged in intense and daily workouts, often two daily sessions (for 3-6 hours), 7/7, for more than 10 months a year, needs per day. We can immediately say that, compared to the general population, and with the exception of some sports, (see below) the recommended amount of protein is greater.

Metabolic fate of proteins at rest and during exercise

In a healthy adult subject engaged in a non-competitive physical activity, the daily protein requirements is about 0.85 g/kg desirable body weight, as shown by WHO.
Proteins turnover in healthy adults, about 3-4 g/kg body weight/day (or 210-280 g for a 70 kg adult), is slower for the muscle than the other tissues and decreasing with age, and is related to the amount of amino acids in the diet and protein catabolism.
At rest the anabolic process, especially of synthesis, uses about 75% amino acids while the remaining 25% undergoes oxidative process, that will lead to CO2 and urea release (for the removal of ammonia).
During physical activity, as result of the decreased availability of sugars, i.e. muscle glycogen and blood glucose used for energy purposes, as well as the intervention of cortisol, the percentage of amino acids destinated to anabolic processes is reduced while it increases that of amino acids diverted to catabolic processes, that is, it occurs an increase in the destruction of tissue proteins.
At the end of physical activity, for about two hours, anabolic processes remain low whereupon it occurs their sharp increase that brings them to values ​​higher than basal ones, so, training induces an increase in protein synthesis even in the absence of an increase in proteins intake.

What determines the daily protein requirements?

There are many factors to be taken into account in the calculation of the daily protein requirements.

  • The age of the subject (if, for example, he/she is in the age of development).
  • Gender: female athletes may require higher levels as their energy intake is lower.
  • An adequate carbohydrate intake reduces their consumption.
    During physical activity, glucogenic amino acids may be used as energy source directly in the muscle, after their conversion to glucose in the liver through gluconeogenesis.
    An adequate carbohydrate intake before and during prolonged exercise lowers the use of body proteins.
  • The amount of carbohydrates stored in muscles and liver (glycogen) (see above).
  • The energy intake of the diet.
    A reduced energy intake increases protein requirements; conversely, the higher energy intake, the lower the amount of protein required to achieve nitrogen balance; usually there is a nitrogen retention of 1-2 mg per kcal introduced.
    If the athlete is engaged in very hard competition/workouts, or if he requires an increase in muscle masses (e.g. strength sports) nitrogen balance must be positive; a negative balance indicates a loss of muscle mass.
    The nitrogen balance is calculated as difference between the nitrogen taken with proteins (equal to: g. proteins/6.25) and the lost one (equal to: urinary urea in 24 hours, in g., x0.56]; in formula:

Nb (nitrogen balance) = (g. protein/6.25) – [urinary urea in 24 hours, in g., x0.56)]

  • The type of competition/workouts that the athlete is doing, either resistance or endurance, as well as the duration and intensity of the exercise itself.
    Resistance training leads to an increase in protein turnover in muscle, stimulating protein synthesis to a greater extent than protein degradation; both processes are influenced by the recovery between a training and the next one as well as by the degree of training (more training less loss).
    In the resistance and endurance performances the optimal protein requirements in younger people as for those who train less time are estimated at 1.3 to 1.5 g protein/kg body weight, while in adult athletes who train more time is slightly lower, about 1-1.2 g/Kg of body weight.
    Why?
    In subjects engaged in a hard physical activity, proteins are used not only for plastic purposes, which are incremented, but also for energy purposes being able to satisfy in some cases up to 10-15% of the total energy demand.
    Indeed, intense aerobic performances, longer than 60 minutes, obtain about 3-5% of the consumed energy by the oxidation of protein substrates; if we add to this the proteins required for the repair of damaged tissue protein structures, it results a daily protein demand about 1.2 to 1.4 g/kg body weight.
    If the effort is intense and longer than 90 minutes (as it may occur in road cycling, running, swimming, or cross-country skiing), also in relation to the amount of available glycogen in muscle and liver (see above), the amount of proteins used for energy purposes can get to satisfy, in the latter stages of a prolonged endurance exercise, 15% of the energy needs of the athlete.
  • The physical condition.
  • When needed, the desired weight.
    Athletes attempting to lose weight or maintain a low weight may need more proteins.

From the above, protein requirements don’t exceed 1.5 g/kg body weight, also for an adult athlete engaged in intense and protracted workouts, while if you consider the amount of protein used for energy purposes, you do not go over 15% of the daily energy needs.
So, it’s clear that diets which supply higher amounts (sometimes much higher) of proteins aren’t of any use, stimulate the loss of calcium in bones and overload of work liver and kidney. Moreover, excess proteins don’t accumulate but are used to fat synthesis.

How to meet the increased protein requirements of athletes

Protein Requirements
Fig. 2 – Road Cycling

A diet that provides 12 to 15% of its calories from protein will be quite sufficient to satisfy the needs of almost all of the athletes, also those engaged in exhausting workouts.
In fact, with the exception of some sports whose energy expenditure is low, close to that of sedentary subject (for example: shooting, or artistic and rhythmic gymnastics), athletes need a high amount of calories and, for some sports such as road cycling, swimming or cross-country skiing, it may be double/triple than that of a sedentary subject.
The increase in food intake is accompanied by a parallel increase in protein intake, because only a few foods such as honey, maltodextrin, fructose, sugar and vegetable oils are protein-free, or nearly protein-free.

Calculation of protein requirements of athletes

If you consider an energy demand of 3500 kcal/die, with a protein intake equal to 15% of total daily calories, you have:

3500 x 0.15 = 525 Kcal

As 1 gram of protein contains 4 calories, you obtain:

525/4 = 131 g of proteins

Dividing the number found by the highest protein requirements seen above (1.5 g/kg body weight/day), you obtain:

131/1.5 = 87 kg

that is, the energy needs of a 87 kg athlete engaged in intense workouts are satisfied.
Repeating the same calculations for a caloric intake of 5000 , you obtain  187 g of protein; dividing it by 1.5 the result is 125 kg, that is, the energy needs of a 125 kg athlete are satisfied.
These protein intakes can be met by a Mediterranean-type diet, without protein or amino acids supplements.

References

Giampietro M. L’alimentazione per l’esercizio fisico e lo sport. Il Pensiero Scientifico Editore. Prima edizione 2005

Protein and amino acid requirements in human nutrition. Report of a joint FAO/WHO/UNU expert consultation. 2002 (WHO technical report series ; no. 935) [PDF]

Omega-6 polyunsaturated fatty acids

The synthesis of omega-6 polyunsaturated fatty acids

Omega-6 polyunsaturated fatty acids are the major polyunsaturated fatty acids (PUFA) in the Western diet (about 90% of all of them in the diet), being components of most animal and vegetable fats.

Omega-6 polyunsaturated fatty acids and linoleic acid

Metabolism of Omega-6 Polyunsaturated Fatty Acids
Fig. 1 – Metabolism of Omega-6 Polyunsaturated Fatty Acids

Within the omega-6 (ω-6) family, linoleic acid is one of the most important and widespread fatty acids and the precursor of all omega-6 polyunsaturated fatty acids. It is produced de novo from oleic acid (an omega-9 fatty acid) only by plant in a reaction catalyzed by Δ12-desaturase, i.e. the enzyme that forms the omega-6 polyunsaturated fatty acid family from omega-9 one.
Δ12-desaturase catalyzes the insertion of the double bond between carbon atoms 6 and 7, numbered from the methyl end of the molecule.
Linoleic acid, together with alpha-linolenic acid, is a primary product of plant polyunsaturated fatty acids synthesis.
Animals, lacking Δ12-desaturase, can’t synthesize it, and all the omega-6 polyunsaturated fatty acid family de novo, and they are obliged to obtain it from plant foodstuff and/or from animals that eat them; for this reason omega-6 polyunsaturated fatty acid are considered essential fatty acids, so called EFA (the essentiality of omega-6 polyunsaturated fatty acids, in particular just the essentiality of linoleic acid, was first reported in 1929 by Burr and Burr).

Omega-6 polyunsaturated fatty acids: from linoleic acid to arachidonic acid

Animals are able to elongate and desaturase dietary linoleic acid in a cascade of reactions to form very omega-6 polyunsaturated fatty acids.
Linoleic acid is first desaturated to gamma-linolenic acid, another important ω-6 fatty acid with significant physiologic effects, in the reaction catalyzed by Δ6-desaturase. It is thought that the rate of this reaction is limiting in certain conditions like in the elderly, under certain disease states and in premature infants; for this reason, and because it is found in relatively small amounts in the diet, few oils containing it (black currant, evening primrose, and borage oils) have attracted attention.
In turn gamma-linolenic acid may be elongated to dihomo-gamma-linolenic acid by an elongase (it catalyzes the addition of two carbon atoms from glucose metabolism to lengthen the fatty acid chain) that may be further desaturated in a very limited amount to arachidonic acid, in a reaction catalyzed by another rate limiting enzyme, Δ5-desaturase.
Arachidonic acid can be elongated and desaturated to adrenic acid.

It should be noted that polyunsaturated fatty acids in the omega-6 family, and in any other n-families, can be interconverted by enzymatic processes only within the same family, not among families.

C-20 polyunsaturated fatty acids belonging to omega-6 and omega-3 families are the precursors of eicosanoids (prostaglandins, prostacyclin, thromboxanes, and leukotrienes), powerful, short-acting, local hormones.

While the deprivation of omega-3 polyunsaturated fatty acids causes dysfunction in a wide range of behavioral and physiological modalities, the omission in the diet of omega-6 polyunsaturated fatty acids results in manifest systemic dysfunction.

In plant seed oils omega-6 fatty acids with chain length longer than 18 carbons are present only in trace while arachidonic acid is found in all animal tissues and animal-based food products.

References

Akoh C.C. and Min D.B. “Food lipids: chemistry, nutrition, and biotechnology” 3th ed. 2008

Aron H. Uber den Nahvert (On the nutritional value). Biochem Z. 1918;92:211–233 (German)

Bender D.A. “Benders’ dictionary of nutrition and food technology”. 2006, 8th Edition. Woodhead Publishing. Oxford

Bergstroem S., Danielsson H., Klenberg D. and Samuelsson B. The enzymatic conversion of essential fatty acids into prostaglandins. J Biol Chem 1964;239:PC4006-PC4008 [Full Text]

Burr G. and Burr M. A new deficiency disease produced by the rigid exclusion of fat from the diet. J Biol Chem 1929;82:345-67 [Full Text]

Chow Ching K. “Fatty acids in foods and their health implication” 3th ed. 2008

Cozzani I. e Dainese E. “Biochimica degli alimenti e della nutrizione”. Piccin Editore, 2006

Mahan L.K., Escott-Stump S.: “Krause’s foods, nutrition, and diet therapy” 10th ed. 2000

Rosenthal M.D., Glew R.H. Mediacal biochemistry. Human metabolism in health and disease. John Wiley & Sons, Inc. 2009

Shils M.E., Olson J.A., Shike M., Ross A.C.: “Modern nutrition in health and disease” 9th ed. 1999

Stipanuk M.H.. Biochemical and physiological aspects of human nutrition. W.B. Saunders Company-An imprint of Elsevier Science, 2000

Van D., Beerthuis R.K., Nugteren D.H. and Vonkeman H. Enzymatic conversion of all-cis-polyunsaturated fatty acids into prostaglandins. Nature 1964;203:839-41