PROTEIN SYNTHESIS: WHAT IT IS AND HOW IT WORKS

Premise: We still know very little about how the human body works. The knowledge we have today is not absolute certainty, only what has currently been discovered. Tomorrow it could change. Let's think about the scientific knowledge of 500 years ago and imagine what it might be in 500 years. We must recognize that we still know very little and therefore remain open and flexible.

Our bodies evolved over millions of years very differently from how we live today: we moved a lot, were often outdoors, and food wasn't always available. Therefore, we had good muscle mass, weren't overweight, and didn't live indoors in a box with artificial light. Technology has made our lives much easier, but today we are too sedentary. Up until 100 years ago, our lives were much more active: physically demanding jobs, doing laundry by hand, and walking a great deal. So today, our bodies are in a completely different condition compared to how they evolved over millions of years: sedentary lifestyle and excess nourishment. The result is there for all to see: metabolic diseases, being overweight, and frailty. Improving the situation is possible: eat food quantities that are adequate for our energy needs and move our bodies to maintain good muscle mass.

At the bottom of the page, you'll find a printable PDF and further in-depth information for experts, explaining the methods used to calculate protein synthesis (a bit technical). It also covers the main researchers in the field, the focus of their research, and a checklist for reading an article on muscle protein synthesis.

We would be VERY happy to know what you think of this in-depth analysis or if you have any questions, please comment below.

PROTEIN RENEWAL
The human body continuously renews all organs and tissues: some proteins are degraded (broken down) and then resynthesized (rebuilt).

Different tissues in the body have very different rates of renewal. The intestinal epithelium renews itself at a rate of 25–30% per day, so it is completely renewed every 3–4 days! Bone renews itself much more slowly: only 5–10% per year.

Proteins are made of amino acids, and the body uses:
amino acids obtained from the degradation of old proteins
– amino acids produced de novo by the body (defined as non-essential amino acids)
– amino acids introduced through diet (defined as essential amino acids)

According to current estimates, the body renews approximately 300g of protein each day. Most of the amino acids from protein breakdown are reused, but some are no longer usable and must be replaced by new amino acids obtained from the diet. If these are scarce, the body sacrifices skeletal muscle (1,2,3) because other organs and tissues, vital for our survival, absolutely need them. When this happens, muscle mass is lost.

PROTEIN SYNTHESIS
When we talk about protein synthesis, we think of muscle, but in reality, most of the protein synthesis that occurs daily involves other organs and tissues.

Fascinating: 30–40% of the amino acids obtained from the diet are retained by the liver and intestines (4). The rest enters the bloodstream, where it is pre-metabolized by organs, tissues, and muscles. Only 10–20% is utilized by the muscles. (5)

MUSCLE MASS AND LONGEVITY
Today, muscle is defined as the “organ of longevity”; the more muscle mass we have, the greater our chances of living a long and healthy life. (6)

Unfortunately, as the years go by, muscle mass is lost (sarcopenia) because:
The muscle is less sensitive to stimuli that trigger muscle synthesis (anabolic resistance).
2) increased protein degradation, due to age and exacerbated by:
– low-grade chronic inflammation
low-protein diet
3) Reduction of hormones that stimulate growth and tissue renewal: testosterone, estrogen, growth hormone, IGF-1. When they decrease, our body renews itself less and therefore ages.

Fortunately, it is possible to preserve muscle mass even as you age thanks to:
endurance training (dominant factor 85-90%)
adequate protein intake

To illustrate the importance of movement, let’s look at the results of an interesting study involving 28 healthy young men who had a single leg placed in a cast for one week: during this brief period of immobilization, muscle protein synthesis decreased by 28% (7).

Imagine the effect on our bodies of decades of sedentary living...

MUSCLE MASS BENEFITS
Better blood sugar management, therefore better metabolic health (8)
Greater energy expenditure, therefore greater possibility of maintaining a healthy weight
Increased bone density, therefore reduced risk of fractures (9)
Increased chances of survival in cases of serious illnesses, for example, cancer (10)
Greater chance of returning to normal after a fracture over 65
Greater mobility, balance, and independence in later life

Muscle Protein Synthesis
When it comes to muscle protein synthesis, there are many false beliefs. Let's look at the current scientific evidence.

The world's most relevant researchers on muscle protein synthesis are:
Robert R. Wolfe, the father of the field
Stuart M. Phillips defined the specific rules of protein intake
Luc van Loon, the most pragmatic, created a bridge between the laboratory and real life.

Important: Initially, studies were conducted only with mixtures of essential amino acids, then with protein powders, and only recently with real food. This has made it possible to understand that real food is superior because it takes longer to digest and therefore provides amino acids for a longer period of time.

The following information refers to the normal, healthy population. Not professional athletes. Remember: these are not absolute and definitive truths, simply what has been discovered to date.

How much protein should I consume?
1.2 – 1.6 g per kg of body weight (ideal weight)
Donna, target weight 60 kg: 72 – 96 g protein
Man, ideal weight 80 kg: 96 – 128 g protein

For the average Italian population, these are the reference ideal weights based on average height: woman 165 cm, man 178 cm. Very often people overestimate their ideal weight and therefore overestimate their protein needs.

Increasing protein intake beyond 1.6 g per kg of body weight offers minimal benefits in general terms and particularly in increasing muscle mass (11). Higher protein intakes (up to 2g/kg) are only useful in particular conditions: malnourished elderly individuals, severe illnesses, post-traumatic recovery, and severely burned patients.
“Going beyond 1.6g won't give you bigger biceps, just more expensive pee” Stuart Phillips

Protein intake: are only noble proteins counted, or all of them?
All proteins should be included in the calculation of daily protein intake: animal, plant, high or low quality.

How many proteins in a single meal?
25-30 g of animal protein, which contain 2-2.5 g of leucine. Over 65 years of age: 3 g of leucine are necessary to activate protein synthesis. (12,13)
Plant proteins: being low in essential amino acids, it is necessary to increase the quantity and combine sources.

Is there a protein limit per meal?
It was once thought that 20 g maximized muscle protein synthesis, then a groundbreaking study by van Loon came out showing that the body can also utilize 100 g of protein in a single meal for muscle protein synthesis. (17) Furthermore, given what happens in some animals (snakes and crocodiles), it is hypothesized that this number could be higher, but to date, we still do not have scientific evidence regarding this.

Animal protein or plant protein: is there a difference?
Yes, there is a big difference: plant-based proteins do not contain essential amino acids in adequate amounts and are more difficult to digest. These problems can be overcome by increasing the quantity (and therefore calories) and combining sources (explained later).

A study conducted in the Netherlands on 16 healthy older adults found that a typical omnivorous meal based on animal protein stimulated muscle protein synthesis by approximately 47% more than a vegan meal, with the same protein and calorie content (18)

Vegan egg white	Omnivorous diet
200 g quinoa	100 g lean beef
95g of soy	200g potatoes
95 g of fava beans	150 g of green beans
95 g of chickpeas	200 g of apple mousse
15 g soy sauce	24 g of herb butter

Both meals contain 600 calories and 36g of protein each.

Interesting: plant-based protein powders (soy protein, pea protein, etc.) are more easily digestible than proteins in legumes and cereals, and therefore are as efficient as animal proteins for muscle protein synthesis (19).

Does intermittent fasting decrease protein synthesis?
No, if the correct amount of protein (1.2-1.6 g/kg) is assumed throughout the rest of the day, protein synthesis remains the same.

Should you consume protein immediately after a workout?
Myth now debunked: the anabolic window lasts 24-48 hours (20), with some suggesting even 72 hours (21). Therefore, there's no need to consume a shake immediately after training; it's sufficient to meet your protein intake throughout the day without stressing.

What stimulates muscle protein synthesis?
The anabolic stimuli (which initiate muscle protein synthesis) are two: the presence of 2-2.5 g of leucine in a meal and resistance training.

If 2.5 g of leucine are not consumed per meal, does protein synthesis not start?
Protein synthesis still occurs when the threshold of 2.5 g of leucine is not reached, but it is not optimal.

Do carbohydrates serve the purpose of muscle protein synthesis?
Another false myth: in studies on muscle protein synthesis, carbohydrates are never used because they are not necessary. Many years ago, it was thought they were needed because they raise insulin, which is necessary for the muscle synthesis process. In reality, proteins stimulate insulin to sufficient levels. (22) Carbohydrates are used to replenish muscle glycogen stores. If you are not an athlete who needs immediate replenishment, the food consumed throughout the day is enough to refill glycogen stores.

Do BCAA 2.1.1 also stimulate muscle synthesis after training, or only EAAs?
Both stimulate muscle synthesis, but the stimulation provided by BCAAs (branched-chain amino acids) is short-lived because they lack the other necessary amino acids (23). With EAAs (essential amino acids), the stimulation lasts longer because they also provide the other amino acids. Important: Free-form amino acids (BCAAs, EAAs) are digested and absorbed into the bloodstream very quickly. Their high availability over a short period of time means that not all of them can be used for protein synthesis, so some of the amino acids are oxidized (24). When you eat actual food, however, absorption into the bloodstream is slower, resulting in less oxidation.

Are protein powders or essential amino acids useful?
For most of the population, no, it's enough to meet your protein quota through food.
Essential amino acids and protein powders can be useful in specific contexts:
– during a significant caloric restriction
– for the elderly or hospitalized patients who do not consume sufficient quantities of protein

After 65 years, does the body use protein?
Beyond a certain age, muscles do not respond as they used to to stimuli that determine muscle protein synthesis (anabolic resistance). Resistance training and increased protein intake compensate for this phenomenon. If protein digestion is difficult, hydrolyzed protein powders or essential amino acid mixtures rich in leucine can be used. (25, 26, 27)

Is it okay to train on an empty stomach?
Yes, that's fine. Current evidence does not indicate differences in muscle mass growth. (28)

Does it make sense to take EAAs before going to sleep on rest days from training?
All researchers state that it is better to consume whole foods rather than protein powders or essential amino acids, and that it is sufficient to consume adequate protein intake over a 24-hour period.

Difference between collagen and whey, can they be combined?
Yes, they can be combined, but it doesn't provide benefits for muscle protein synthesis. Sometimes a study (29) by van Loon is cited where 5g of collagen and 25g of whey stimulate muscle protein synthesis. There's a problem, though: the control group takes nothing, only water. To demonstrate that collagen makes a difference, the control group should have taken only whey. Professor van Loon's group is currently studying how collagen supplementation affects the protein synthesis of collagen-rich tissues. Muscle is not rich in collagen.

When is too much protein too much? Is it bad for your kidneys?
If your kidneys are healthy, protein does not harm them; in fact, it's beneficial. We've dedicated an entire chapter to this topic to explain how this misconception originated.

What is the correct amino acid ratio?
Il fabbisogno giornaliero umano di aminoacidi essenziali determinato dalla FAO nel 2007 (30) è riportato nella tabella sottostante. ATTENZIONE: questo è il fabbisogno minimo per non avere carenze. Come si può vedere, un’alimentazione con proteine animali supera ampiamente questo fabbisogno minimo. Oggi non è ancora stato determinato quale sia il fabbisogno ottimale. Le proteine contenute nel cibo apportano sufficienti quantità, quindi non sono necessari aminoacidi essenziali o whey.

Bistecca o macinato?
Il macinato viene digerito meglio e quindi più aminoacidi compaiono sono disponibili nel flusso sanguigno. Importante masticare bene. (31)

Mangiare dritti o sdraiati fa la differenza?
Mangiare diritti facilita la digestione e quindi la quantità di aminoacidi assorbiti. (32)

Queste due ultime considerazioni sono importanti quando ci sono pazienti allettati, che magari consumano poche proteine.

Curiosità: l’immersione in acqua fredda immediatamente dopo l’allenamento riduce la sintesi proteica muscolare perché diminuisce l’afflusso di sangue al muscolo. Oggi non si sa cosa accade quando ci si immergere prima, diverse ore dopo o il giorno successivo all’allenamento. (33)

DIGERIBILITÀ DELLE PROTEINE
Le proteine sono molecole molto grandi che nel processo digestivo vengono “tagliate” fino a ottenere singoli aminoacidi che possono essere assorbiti dall’intestino.

Le proteine vegetali sono più difficili da digerire perché spesso sono “intrappolate” in matrici cellulari e contengono antinutrienti (fitati, fibre, inibitori enizmatici). Per questo i loro aminoacidi sono meno disponibili per essere assorbiti.

% di assorbimento intestinale (34):
proteine animali 90-98%
proteine vegetali 70-90%

Questi dati dimostrano che il nostro apparato digerente è ottimizzato per digerire proteine animali, contrariamente a quanto viene spesso raccontato. Chiaramente si adatta anche a quelle vegetali ma è meno efficiente.

PROTEIN QUALITY
Il metodo più moderno per valutare la qualità delle proteine è il DIASS, che prende in considerazione il contenuto di aminoacidi essenziali e la digeribilità delle varie fonti proteiche (34).

Sopra a 100 ottima qualità, fino a 75 buona, sotto limitata.
Milk powder 144
Bacon 142
Whey concentrate                             133
Ribeye (costata)                                 130
Uova                                                   122
Jerky di manzo                                   120
Farina di soia                                      105

L’unica proteina vegetale con valore sopra a 100 è la farina di soia, perché è l’unico vegetale con la sufficiente quantità di aminoacidi essenziali. Lista completa here. Se si decide di consumare soia, sceglierla biologica, la soia convenzionale è OGM e viene coltivata utilizzando grandi quantitativi di glifosato.

Per sopperire alla carenza di alcuni aminoacidi essenziali, le proteine vegetali vanno combinate: legumi (carenti di metionina e cisteina) insieme a cereali (carenti di lisina). Questi sono i piatti tradizionali delle popolazioni povere: riso e lenticchie, pasta e ceci, riso e bisi, riso e fagioli.

Il problema di queste combinazioni è che apportano molte più calorie: per raggiungere il contenuto di proteine e leucina in 130 g di petto di pollo bisogna consumare 95 g di lenticchie secche insieme a 122 g di riso. Questa combinazione apporta 710 calorie, contro 130 calorie del pollo.

QUALI PROTEINE CONSUMARE?
Le migliori proteine sono animali perché contengono aminoacidi essenziali nelle quantità e nelle  proporzioni adeguate al fabbisogno umano. Inoltre sono ricche di leucina, necessaria per stimolare un’ottimale sintesi proteica.

In questa tabella sono riportati i grammi di alimento (crudo) che apportano 2,5 g di leucina, ordinato per calorie crescenti. Viene riportato anche il contenuto proteico e calorico della porzione.

Le uniche fonti vegetali che apportano quantità di leucina adeguate sono le proteine isolate di soia e la spirulina. Tutte le altre fonti vegetali vanno consumate in grandi quantità per apportare 2,5 g di leucina (circa 450 g di fagioli borlotti o di ceci).

Lista completa here.

LE PROTEINE DANNEGGIANO I RENI?
Questa è una credenza errata e ancora dura a morire. Per comprenderne l’infondatezza analizziamo come si è generata:

– tra fine 1800 e inizio 1900 si osservò che nei pazienti con insufficienza renale diete ricche di proteine aumentavano l’urea nel sangue
– negli anni 50 si osservò che le proteine aumentavano il filtrato glorumerale (GFR)
– negli anni 60 si consolida l’idea che le proteine aumentino il lavoro dei reni
– negli anni 80 Barry Brenner formula un’ipotesi: l’iperfiltrazione (aumento del “normale” GFR) danneggia i glomeruli. È solo un’idea intuitiva non supportata da evidenze, un po’ come la “lipid hypothesis” di Ancel Keys su grassi saturi e malattie cardiovascolari.
– negli anni 90 l’idea si è ormai diffusa: una dieta ricca di proteine può “consumare” il rene
– negli anni 90 iniziano ad arrivare i risultati dei primi studi dove emerge che in realtà le proteine non diminuiscono la funzionalità renale. L’ipotesi inizia a vacillare
– nel 2005 le linee guida americane smentiscono definitivamente l’ipotesi in quanto l’evidenza dimostra che in realtà sia un minor apporto proteico a diminuire la funzione renale (35)

Quali sono le più solide evidenze scientifiche oggi:
– Il GFR aumenta quando si mangiano più proteine, ma questo non è un problema, è un adattamento fisiologico normale (36)
– le proteine non sono la causa del declino del GFR che si osserva con l’avanzare dell’età (37)
– un consumo proteico più elevato è associato a un rischio ridotto di sviluppare malattia renale cronica (38)

Quarant’anni fa si pensava che l’aumento del filtrato glorumerale (GFR) dovuto a un maggior consumo di proteine potesse danneggiare i reni, oggi invece è considerato un normale adattamento fisiologico, che aumenta la capacità di eliminare urea, creatinina, metaboliti e tossine.

Chiaramente questo discorso è valido solo per reni sani, quando i reni sono malati non riescono a fare il loro lavoro. Nei reni malati la capacità di eliminare l’azoto è ridotta, quindi l’apporto proteico viene spesso modulato per evitare accumulo di urea.

Quindi perché ci sono ancora medici che ritengono che le proteine danneggino i reni? Perché le errate credenze scientifiche ci mettono decenni per correggersi. Il fisico Max Plank diceva “una nuova verità scientifica non trionfa convincendo i suoi oppositori, ma perché questi muoiono e cresce una nuova generazione.”

LE PROTEINE DANNEGGIANO IL FEGATO?
Per quanto riguarda il fegato la storia è simile:
– il fegato è dove gli aminoacidi che non vengono utilizzati per la sintesi proteica vengono “smontanti” e l’azoto in essi contenuti viene trasformato in urea
– da questo meccanismo nacque l’idea: più proteine, più lavoro per il fegato
– nei fegati malati (cirrosi e insufficienza epatica) il fegato non è in grado di gestire correttamente l’urea
– anche in questo caso si estese una caratteristica del fegato malato a soggetti sani

Oggi sappiamo che un fegato sano non ha alcun problema a gestire l’urea e che diete con un adeguato apporto proteico non danneggiano il fegato, al contrario! (39) Il fegato trattiene moltissimi degli aminoacidi che assumiamo con il cibo, perché ne ha bisogno per produrre diverse molecole tra cui albumina, enzimi e ormoni.

I CATABOLITI AZOTATI FANNO MALE?
I cataboliti azotati sono i prodotti di scarto derivanti dal metabolismo degli aminoacidi e delle altre molecole azotate presenti nel corpo. Si chiamano “azotati” perché contengono azoto.

I principali cataboliti azotati sono:
urea, 80-90%, deriva da aminoacidi deaminati (a cui viene tolto l’azoto) dal fegato (40)
ammonio, 5-10%, prodotto nel rene a partire dalla glutammina, utilissimo per bilanciare pH
creatinina, 2-5%, deriva dalla creatina muscolare, poco influenzato dall’alimentazione
acido urico, 1-2%, deriva dalle purine (basi azotate in DNA e RNA, ATP, coenzimi)

Il principale catabolita azotato è l’urea, che deriva principalmente dal rinnovo proteico quotidiano. L’urea è una cosa normalissima, la semplice conseguenza del rinnovo proteico necessario a mantenere il corpo sano. IMPORTANTE: l’urea non è un “rifiuto” in senso stretto, ma l’inevitabile surplus di azoto del metabolismo proteico.

QUANTA UREA PUÒ GESTIRE IL CORPO
Nelle linee guida non esiste un limite massimo di assunzione di proteine (41)

Sappiamo però che il ciclo dell’urea è limitato e dipende dal peso del corpo. Tenendo conto di questo limite, la quantità massima di proteine stimata a oggi è: (42)
Peso 60 kg = 210 – 258 g proteine (3,5 – 4,3 g/kg)
Peso 80 kg = 285 – 365 g proteine (3,5 – 4,6 g/kg)

Nonostante questi numeri i ricercatori oggi ritengono che il limite assolutamente sicuro sia: 3,5 g di proteine per kg di peso (forma).

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