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Protein life times are, on average, not particularly long, on a human life timescale. I was wondering, how old is the oldest protein in a human body? Just to clarify, I mean in terms of seconds/minutes/days passed from the moment that given protein was translated. I am not sure is the same thing as asking which human protein has the longest half-life, as I think there might be "tricks" the cell uses to elongate a given protein's half-life under specific conditions.
I am pretty sure there are several ways in which a cell can preserve its proteins from degradation/denaturation if it wanted to but to what extent? I accept that a given protein post-translationally modified still is the same protein, even if cut, added to a complex, etc. etc.
And also, as correlated questions: does the answer depend on the age of the given human (starting from birth and accepting as valid proteins translated during pregnancy or even donated by the mother)? What is the oldest protein in a baby's body and what is in a elderly's body? How does the oldest protein lifetime does in comparison with the oldest nucleic acid/cell/molecule/whatever in our body?
Crystallin proteins are found in the eye lens (where their main job is probably to define the refractive index of the medium); they are commonly considered to be non-regenerated. So, your crystallins are as old as you are!
Because of this absence of regeneration, the accumulate damage over time, including proteolysis, cross-linkings etc., which is one of the main reasons why visual acuity decays after a certain age: that is where cataracts come from. The cloudy lens is the result of years of degradation events in a limited pool of non-renewed proteins.
Edit: A few references:
This article shows that one can use 14C radiodating to determine the date of synthesis of lens proteins, because of their exceptionally low turnover: Lynnerup, "Radiocarbon Dating of the Human Eye Lens Crystallines Reveal Proteins without Carbon Turnover throughout Life", PLoS One (2008) 3:e1529
This excellent review suggested by iayork (thanks!) lists long-lived proteins (including crystallins) and how they were identified as such: Toyama & Hetzer, "Protein homeostasis: live long, won't prosper" Nat Rev Mol Cell Biol. (2013) 14:55-61
I like Mowgli's answer, because it is a non-obvious example. However I would also point out that there are many, many protein-based structural components in the body that we know do not regenerate due to associated pathologies; so presumably these structural proteins are as old as from when they first arose in developemnt. Take the stereocilia on hair cells in the cochlea, for instance. The stereocilia structure is actin-filament based, so is a structural protein. Hearing loss occurs due to damage to these structures, which is not repaired. In fact, birds suffer only temporary hearing loss not because they regenerate these structures, but because they grow replacement hair cells.
Once you start thinking about this then, it is pretty clear that many structural proteins will be conserved throughout life (if the cell they are attached to or within remains a part of the body). And many cells of the body remain in the body throughout life, so any proteins that join the cells together, say connexin proteins that form tight junctions between cells, would also presumably be conserved. I say this because I think the energetic cost of degrading a protein that spans two membranes would be too great for it to occur. I have not hear of tight junctions being eliminated, but I may be wrong.
Mowgli's answer is nice because it involves globular rather than fibrous proteins- though Wikipedia still classifies them as structural proteins. I was interested and read this article about them. Interesting stuff! Thank you Mowgli!
I would be interested to know if there are any conserved biochemically active proteins. I would think that extracellular proteins would probably be turned over, and the best chance of finding such a conserved protein would be within a cell that remains for life post differentiation. Perhaps a proteosome complex itself (these are the protein complexes that are involved in protein degradation)? I don;t think ribosomes are degraded either, but I don't find this a very satisfactory example!
A very interesting example are the cohesin molecules holding sister chromatids together in the oocytes (so only applicable to females, sorry!). Cohesion is established in utero, and these molecules are not recycled throughout life (AFAIK only shown directly for mice, not humans - https://www.ncbi.nlm.nih.gov/pubmed/20971813, https://www.ncbi.nlm.nih.gov/pubmed/26898469, but presumably same is true for us). This is considered to be a major contributor to the maternal age effect (https://en.wikipedia.org/wiki/Age_and_female_fertility) through low level loss of cohesion throughout life (since levels of cohesin can't be restored) until chromosomes start losing association between sisters which causes high chances of their missegregation (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536066/)
In terms of the common/abundant proteins, the answer would have to be elastin.
The turnover is extremely slow, with a half-life of 74 years (https://www.elastagen.com/media/The_Science_of_Elastin.pdf) or "decades" according to other sources. In any case it is very slow - slow enough that most of it lasts a lifetime.
Elastin is a major constituent of the extracellular matrix but the rate of synthesis (and breakdown) is much slower than collagen (the other major structural protein). While breakdown is extremely slow, synthesis is even slower and may not be sufficient to replace the lost elastin, resulting in decreased levels with age. This is one of the primary contributions to the aged look of older humans
In chemistry and biochemistry, the acidity of a solution is called pH. Solutions with low pH -- values less than 7 -- are acidic, while solutions with pH higher than 7 are basic. A pH of 7 is considered neutral. Your body pH is slightly on the basic side of neutral, explain Reginald Garrett and Charles Grisham in their book "Biochemistry," because: * normal values run around 7.4 1. The buffer systems in and outside cells help maintain that pH.
- In chemistry and biochemistry, the acidity of a solution is called pH.
- Solutions with low pH -- values less than 7 -- are acidic, while solutions with pH higher than 7 are basic.
- Your body pH is slightly on the basic side of neutral, explain Reginald Garrett and Charles Grisham in their book "Biochemistry," because: * normal values run around 7.4 1.
The Production of a Protein
Proteins are one of the most abundant organic molecules in living systems and have an incredibly diverse range of functions. Proteins are used to:
- Build structures within the cell (such as the cytoskeleton)
- Regulate the production of other proteins by controlling protein synthesis
- Slide along the cytoskeleton to cause muscle contraction
- Transport molecules across the cell membrane
- Speed up chemical reactions (enzymes)
- Act as toxins
Each cell in a living system may contain thousands of different proteins, each with a unique function. Their structures, like their functions, vary greatly. They are all, however, polymers of amino acids, arranged in a linear sequence (Figure 1).
The functions of proteins are very diverse because they are made up of are 20 different chemically distinct amino acids that form long chains, and the amino acids can be in any order. The function of the protein is dependent on the protein’s shape. The shape of a protein is determined by the order of the amino acids. Proteins are often hundreds of amino acids long and they can have very complex shapes because there are so many different possible orders for the 20 amino acids!
Figure 1 Protein structure. The colored balls at the top of this diagram represent different amino acids. Amino acids are the subunits that are joined together by the ribosome to form a protein. This chain of amino acids then folds to form a complex 3D structure. (Credit: Lady of Hats from Wikipedia public domain)
Contrary to what you may believe, proteins are not typically used as a source of energy by cells. Protein from your diet is broken down into individual amino acids which are reassembled by your ribosomes into proteins that your cells need. Ribosomes do not produce energy.
Figure 2 Examples of foods that contain high levels of protein. (“Protein” by National Cancer Institute is in the Public Domain)
The information to produce a protein is encoded in the cell’s DNA. When a protein is produced, a copy of the DNA is made (called mRNA) and this copy is transported to a ribosome. Ribosomes read the information in the mRNA and use that information to assemble amino acids into a protein. If the protein is going to be used within the cytoplasm of the cell, the ribosome creating the protein will be free-floating in the cytoplasm. If the protein is going to be targeted to the lysosome, become a component of the plasma membrane, or be secreted outside of the cell, the protein will be synthesized by a ribosome located on the rough endoplasmic reticulum (RER). After being synthesized, the protein will be carried in a vesicle from the RER to the cis face of the Golgi (the side facing the inside of the cell). As the protein moves through the Golgi, it can be modified. Once the final modified protein has been completed, it exits the Golgi in a vesicle that buds from the trans face. From there, the vesicle can be targeted to a lysosome or targeted to the plasma membrane. If the vesicle fuses with the plasma membrane, the protein will become part of the membrane or be ejected from the cell.
Figure 3 Diagram of a eukaryotic cell. (Photo credit: Mediran, Wikimedia. 14 Aug 2002)
Insulin is a protein hormone that is made by specific cells inside the pancreas called beta cells. When the beta cells sense that glucose (sugar) levels in the bloodstream are high, they produce insulin protein and secrete it outside of the cells into the bloodstream. Insulin signals cells to absorb sugar from the bloodstream. Cells can’t absorb sugar without insulin. Insulin protein is first produced as an immature, inactive chain of amino acids (preproinsulin – See Figure 4). It contains a signal sequence that targets the immature protein to the rough endoplasmic reticulum, where it folds into the correct shape. The targeting sequence is then cut off of the amino acid chain to form proinsulin. This trimmed, folded protein is then shipped to the Golgi inside a vesicle. In the Golgi, more amino acids (chain C) are trimmed off of the protein to produce the final mature insulin. Mature insulin is stored inside special vesicles until a signal is received for it to be released into the bloodstream.
Figure 4 Insulin maturation. (Photo credit: Beta Cell Biology Consortium, Wikimedia. 2004. This picture is in the public domain.
Exogenous and Endogenous Protein Metabolism | Biology
By the term endogenous protein metabolism is meant the disintegration of those proteins which already exist as components of living cells (tissue proteins). The term exogenous protein metabolism implies the breakdown of food proteins which do not exist as parts of the cell protoplasm.
The classical view of protein metabolism, originally proposed by Folin, is now challenged. Folin’s view was the metabolic patterns of exogenous (dietary) and endogenous (body) protein metabolism differ, i.e., the end products of endogenous protein metabolism are uric acid, creatine and neutral sulphur whereas urea is the end product of exogenous protein metabolism.
However isotopic experiment reveals that the body proteins are in a constant state of turnover and the body proteins are continually broken down and replaced by new proteins synthesized from dietary amino acids. The replacement of protein is rapid in plasma, liver, kidneys and intestinal tract and slow in haemoglobin, muscle and skin.
Dynamic State of Amino Nitrogen and Proteins of the Body:
It has been established by the work of Schoenheimer and others that the amino nitrogen of amino acids (except lysine) is distributed to other amino acids of different tissues and reversibly it is withdrawn from those amino acids to the amino acids which contained amino nitrogen by the process of deamination and reamination.
Protein Storage (Labile Protein):
Nitrogen excreted for the first few days after protein starvation was greater and then becomes more or less con­stant. The disorganized protein present in liver, thymus, prostate, seminal vesicle, alimentary tract, pancreas, spleen and kidneys, etc., are drawn upon to meet the need of the body and these proteins are called labile pro­teins. These are utilized for the synthesis of other proteins and may be oxidized to gain energy when required.
End Products of Protein Metabolism:
The nitrogen released from amino acid (protein) catabolism is excreted from the body in different form which varies in different species of animals. The considerable amount of nitrogen excreted through the urine of men, mammals and amphibians, etc., is urea. The birds and reptiles excrete nitrogen as uric acid mainly. The man also excretes nitrogen of purine bases as uric acid. Creatine excretion is exclusively from tissue protein breakdown. Neutral sulphur excretion does not indicate the nature of dietary or tissue protein breakdown.
Due to dynamic state of amino nitrogen of amino acid and differential pattern of metabolism of labile protein, the excretion of different nitrogenous metabolic end product does not always give real metabolic picture of protein metabolism. But some clue may be obtained if the standardized experiments were done e.g., increased creatine excretion, may indicate increased tissue protein, i.e., specially muscle protein catabolism going on. Increased uric acid excretion may be due to increased purine catabolism. Increased urea excretion may indicate dietary protein catabolism.
Brief Life History of the End Products of Exogenous Protein Metabolism:
From Folin’s experiment, although challenged, it appears that the end products of exogenous protein metab­olism are urea, ammonia, inorganic sulphate and 50% of the total uric acid excreted.
The brief life history of these products is mentioned below:
(a) From deamination of amino acids (mainly from exogenous sources),
(b) From salts like ammonium carbonate, lactate, etc., taken in diet or as drug, and
(c) From the amino acid arginine.
It breaks down into urea and ornithine. The end product of metabolism of these bodies is urea.
20-40 mgm (average 30 mgm) of urea present per 100 ml of blood. Almost equally distributed in plasma and corpuscles.
Functions Served by Urea Formation:
Urea formation helps to maintain the reaction of blood constant. Because, in it, one acid (carbonic acid) and two molecules of ammonia remain neutralized.
An adult taking a normal mixed diet excretes urea through urine an average of 30 gm daily (2% if total urine volume be 1,500 ml). 80% of urinary nitrogen is excreted in the form of urea.
(a) From deamination of amino acids, both exogenous and endogenous. Although deamination takes place chiefly in the liver, recent observations indicate that ammonia is also formed in the kidneys. Ammonia formed in the liver is converted into various substances. Kidneys can deaminate amino acids normally. The amount increases during acidosis and falls in alkalosis, and
(b) Certain ammonium salts taken in food or as drug, e.g., ammonium chloride.
Fate and Functions of Ammonia:
(a) Form Ammonium Salts. The purpose served is to keep the blood reaction constant,
(b) Ammonia may be utilized for the synthesis of amino acid, uric acid, nucleoproteins and other nitrogenous compounds.
With a mixed diet in an adult man the total daily output is about 0.7 gm. Ammonia nitrogen constitutes about 2-4% of total urinary nitrogen.
Relation with Blood Reaction:
In acidosis more ammonium salts will be formed. Reverse changes will take place in alkalosis.
Significance of Variations:
Although ammonia is an end product of exogenous protein metabolism, yet its amount in the urine is determined by the relative proportion of acids and bases in the body. In conditions of acidosis it rises, in alkalosis it falls. Ammonia coefficient is a reliable guide to the condition of acidosis or alkalosis of the body.
They are greatly produced from dietary proteins in the body. Consequently, they may be taken as the end products of exogenous protein metabolism. (The ethereal sulphates have a different life history altogether and has been discussed under ‘Sulphur Metabolism’).
It is an index of both endogenous and exogenous protein metabolism.
Brief Life History of the End Products of Endogenous Protein Metabolism:
From dietetic experiments in dogs it has been found that creatinine and neutral sulphur remain absolutely unchanged. So they are solely of endogenous origin. In this connection, the compound creatine, although not shown in this experiment, but when present in urine, should be regarded as derived from endogenous protein metabolism, because it is the precursor of creatinine.
Thus these compounds are wholly endogenous. Half of uric acid is of endogenous origin and the other half is of exogenous origin. The life history of neutral sulphur has been discussed under Sulphur Metabolism and of uric acid under Uric Acid Metabolism.
A brief summary of the life history of creatine and creatinine is given below:
Methyl guanidoacetic acid.
Total Amount in the Body:
90-120 gm in adult, 98% of it is present in the striated muscle as creatine phosphate. Skeletal muscles contain about 0.5% creatine. It is also found in heart (about half to the amount in skeletal muscles, i.e., 0.25%), testes, brain and uterus, specially during pregnancy.
It is present in blood about 10 mgm per 100 ml and remain mostly in the red cells. As it is present inside the red cells, it is not filtered. Hence, it is usually not present in the urine.
Origin and Formation of Creatine:
(a) Creatine synthesis requires three amino acids, viz., arginine glycine and me­thionine (as S-adenosyl methionine),
(b) The compound guanidoacetic acid is an intermediate step in the synthesis of creatine,
(c) The methyl group of creatine is derived from methionine,
(d) The stages in creatine synthesis appear to be as follows- two organs, i.e., kidneys and liver, are also involved for the complete synthesis of creatine.
In kidneys, glycine and arginine react where amidine group (-CNHNH,) of arginine is transferred to glycine with the forma­tion of guanidoacetic acid (glycocyamine) by the enzyme transamidinase. Transamidinase enzyme is present only in kidneys and pancreas. But this enzymatic reaction mostly takes place in the kidneys.
Methylation of guanidoacetic acid takes place, in the liver, because the liver contains the enzyme guanidoacetic methyl transferase. Guanidoacetic acid is converted into creatine with the help of amino acid, methionine (active form) in presence of enzyme guani­doacetic methyl transferase and glutathione (GSH).
When methyl group of methionine is transferred to guanidoacetic acid to form creatine (methyl guanidoacetic acid), the methionine is converted into S-adenosyl homocysteine. Ac­tivation of methionine takes place by ATP when methionine is converted into S-adenosyl methionine. Recently, it has been shown that in mammals both transamidiantion and methylation reactions, involved in the synthesis of creatine, take place in the pancreas.
Effects of Creatine Feeding:
If creatine is ingested in small amounts (up to 1 gm daily), none is found in the urine, but in moderate amounts (up to 5 gm daily) a little is excreted as creatine and the rest is stored. But if large amounts (20 gm) of creatine be taken, the major part (15 gm) is excreted as such, another part (4.5 gm) is retained and a small part (0.5 gm) is excreted as creatinine in the urine. This shows that creatine is not a waste product. It is useful and there is a store for it in the body.
Until this reservoir is filled up, no creatine will appear in the urine. Creatine synthesis is dependent on kidney transamidinase activity. The kidneys were thought to be the only site of the transamidinating enzyme until recently. However, recent studies have indicated that the pancreas may play a unique role in the synthesis of creatine within the mammalian body.
Interrelation with Creatinine:
These two compounds are closely interrelated. They are readily interconvertible while in solution. Creatinine is anhydride of creatine having one molecule of water less. Acid medium favours the formation of creatinine, whereas alkaline medium favours the formation of creatine. But in vivo creatinine cannot be converted into creatine, although the reverse is the rule.
i. Creatine is converted into creatine phosphate (phosphagen) which takes an essential part in the chemical changes underlying muscular contraction. Creatine, when given in moderate amounts by mouth, disap­pears completely in the body and nothing appears in the urine. This is supposed to be due to its conversion into creatine phosphate and subsequent storage in the muscles.
ii. Creatine certainly has some function in tissues other than muscles but its nature is not known.
ii. Creatine is the precursor of creatinine.
Excretion of Creatine:
Creatine is not generally present in the urine of normal adult males. But it may be excreted abnormally.
Its excretion in the urine is determined by the following factors:
Up to the age of puberty it is constantly present in the urine of both sexes. It has been suggested to be due to an increased production of creatine, induced in some unknown way, by the activity of growth impulse. It may also be due to a lower capacity of the undeveloped muscles for creatine storage. There is a third possibility in that the children possess less power to convert creatine into creatinine.
After puberty it is found intermittently in healthy a female which is not related to menstruation.
It is constantly present during pregnancy. It rises to a maximum of 1.5 gm daily after confinement and is probably derived from the involuting uterus. The sex difference of creatine excretion cannot be properly explained. That increased creatine excretion is not due to the less muscular development in females is proved by the fact that it occurs even in women who are highly trained physically. That sex has something to do here is supported by the observation that creatinuria is common in eunuchs. It may be easily induced in old people (naturally with diminished sex functions) by administration of small amount of creatine.
High protein and low carbohydrate diets increase creatine excretion. The former acts by stimulating tissue metabolism due to its high specific dynamic action. The latter acts indirectly by the absence of its sparing effects upon the breakdown of tissue protein.
v. Increased Tissue Breakdown:
In any condition that increases the breakdown of tissues, specially of striated mus­cles, as in starvation, prolonged diabetes mellitus, hyperthyroidism, fevers and other wasting diseases which increase the basal metabolic rate, the creatine excretion is increased. In certain diseases of muscles (myopathy) where muscles undergo degeneration, a large amount of creatine is excreted.
In such conditions 90% or more creatine appears in an unchanged form in the urine even when it is given by mouth in small amount. This is said to be due to a lower storage capacity of the muscle. It is also probable that in this disease (i.e., myopathy) the reversible enzyme reaction, by which the broken creatine phosphate becomes re-synthesised in the muscle, is absent.
It is the anhydride of creatine.
It is mostly formed from breakdown of creatine phosphate in the body. This process is not catalysed by any enzymes and is irreversible. Creatine-labelled with isotopic 15 N gives creatinine containing same isotopic 15 N.
A large amount in the muscle.
Effects of Creatinine Feeding:
When orally administered nearly 80% is promptly excreted in the urine. Hence, it is considered to be a waste product. It is a no-threshold substance. It is filterd by the glomeruli and is also actively secreted by the tubular cells in the urine. Amount in blood: Normally it is present about 0.7-2.0 mgm per 100 ml. This level is very constant and it is considered to be pathological when its value increases about 2 mgm. Creatinine is also found in bile, sweat and in secretion of stomach and intestine.
About 1.2 -2.0 gm in adult males and 0.8-1.5 gm in adult females are excreted in 24 hours. The amount excreted is remarkably constant for a particular individual. It is related to the muscle bulk and is higher in muscular persons. This stands in great contrast with creatine excretion, which bears no relation to muscular development. The excretion increases during work and exercise but is immediately followed by a fall, so that the daily output remains constant.
Significance of Variation:
Creatinine represents the waste products of creatine metabolism and it arises in the body from the spontaneous breakdown of creation phosphate. It serves practically no function in the body apparently. As its excretion is not related with food protein so its variations in the excretion indicate some of the metabolic disorders. Appearance of creatinine in urine is known as creatinuria when a small amount of creatine is also excreted along with creatinine.
The creatine value gradually decreases as the maturity is advanced. Its excretion increases in fevers, starvation, on a carbohydrate-free diet and in diabetes mellitus. It may increase due to excessive tissue destruction releasing creatine or due to failure of creatine being properly phosphorylated. So creatinine excretion is independent of food proteins and is to be considered as an index of endogenous protein metabolism.
Oxidant-antioxidant system: role and significance in human body
Present article gives a holistic view of the causes, role and conrol of oxidative stress in the development and progression of various human diseases. Several types of reactive species are generated in the body as a result of metabolic reactions in the form of free radicals or non-radicals. These species may be either oxygen derived or nitrogen derived and called prooxidants. They attack macromolecules including protein, DNA and lipid etc. causing cellular/tissue damage. To counter their effect, the body is endowed with another category of compounds called antioxidants. These antioxidants are produced either endogenously or received from exogenous sources and include enzymes like superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, minerals like Se, Mn, Cu and Zn, and vitamins like vitamin A, C and E. Other compounds with antioxidant activity include glutathione, flavonoids, bilirubin and uric acid etc.. In a healthy body, prooxidants and antioxidants maintain a ratio and a shift in this ratio towards prooxidants gives rise to oxidative stress. This oxidative stress may be either mild or severe depending on the extent of shift and remains the cause of several diseases such as cardiovascular diseases, neurological diseases, malignancies, renal diseases, diabetes, inflammatory problems, skin diseases, aging, respiratory diseases, liver diseases and different types of viral infections. As more and more reports are pouring in, a lot of information is being unfolded about oxidative stress in relation to several other diseases.
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Lewy Body Dementia
Not all patients with Parkinson&aposs disease develop dementia, but some do. The condition is known as Parkinson&aposs disease dementia. Lewy bodies also appear in a condition known as Lewy body dementia (which is called dementia with Lewy bodies in some classification systems).
In Parkinson&aposs disease, the Lewy bodies are found mainly in the substantia nigra in the midbrain. In Lewy body dementia, they are mostly spread through the cerebral cortex, or the surface layer of the brain. Dementia develops later in a person with Parkinson&aposs disease (if it appears at all) than in a person with Lewy body dementia.
The two disorders described above are closely related to each other and may be different forms of the same disease. Patients with either disease eventually develop some similar symptoms. The evidence obtained so far indicates that the changes in their brains become more similar as well.
Confusingly, the names for alpha-synuclein diseases vary. For example, some sources classify both Parkinson&aposs disease with dementia and dementia with Lewy bodies as types of Lewy body dementia.
Some Context: Why 1444?
Before we dive into the analysis, first thing’s first—what’s so special about the year 1444?
It was the year of the Battle of Varna. That’s when the Ottoman army defeated the Hungarians and allowed the Ottoman Empire to expand its reign.
It’s considered a pivotal moment for Ottoman expansion into Southern Europe. In fact, this battle is so historically significant, it was chosen as the start date for a popular video game called Europa Universalis IV.
Protein is an essential macronutrient, but not all food sources of protein are created equal, and you may not need as much as you think. Learn the basics about protein and shaping your diet with healthy protein foods.
What Is Protein?
Protein is found throughout the body—in muscle, bone, skin, hair, and virtually every other body part or tissue. It makes up the enzymes that power many chemical reactions and the hemoglobin that carries oxygen in your blood. At least 10,000 different proteins make you what you are and keep you that way.
Protein is made from twenty-plus basic building blocks called amino acids. Because we don’t store amino acids, our bodies make them in two different ways: either from scratch, or by modifying others. Nine amino acids—histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine—known as the essential amino acids, must come from food.
How Much Protein Do I Need?
The National Academy of Medicine recommends that adults get a minimum of 0.8 grams of protein for every kilogram of body weight per day, or just over 7 grams for every 20 pounds of body weight. 
- For a 140-pound person, that means about 50 grams of protein each day.
- For a 200-pound person, that means about 70 grams of protein each day.
The National Academy of Medicine also sets a wide range for acceptable protein intake—anywhere from 10% to 35% of calories each day. Beyond that, there’s relatively little solid information on the ideal amount of protein in the diet or the healthiest target for calories contributed by protein. In an analysis conducted at Harvard among more than 130,000 men and women who were followed for up to 32 years, the percentage of calories from total protein intake was not related to overall mortality or to specific causes of death.  However, the source of protein was important.
“Pure” protein, whether derived from plant or animal foods, probably has similar effects on health, although the mix of amino acids can have health implications. Some proteins found in food are “complete,” meaning they contain all twenty-plus types of amino acids needed to make new protein in the body. Others are incomplete, lacking one or more of the nine essential amino acids, which our bodies can’t make from scratch or from other amino acids. Animal-based foods (meat, poultry, fish, eggs, and dairy foods) tend to be good sources of complete protein, while plant-based foods (fruits, vegetables, grains, nuts, and seeds) often lack one or more essential amino acid. Those who abstain from eating animal-based foods can eat a variety of protein-containing plant foods each day in order to get all the amino acids needed to make new protein, and also choose to incorporate complete plant proteins like quinoa and chia seeds.
It’s important to note that millions of people worldwide, especially young children, don’t get enough protein due to food insecurity. The effects of protein deficiency and malnutrition range in severity from growth failure and loss of muscle mass to decreased immunity, weakening of the heart and respiratory system, and death.
However, it’s uncommon for healthy adults in the U.S. and most other developed countries to have a deficiency, because there’s an abundance of plant and animal-based foods full of protein. In fact, many in the U.S. are consuming more than enough protein, especially from animal-based foods. 
It’s All About the Protein “Package”
When we eat foods for protein, we also eat everything that comes alongside it: the different fats, fiber, sodium, and more. It’s this protein “package” that’s likely to make a difference for health.
The table below shows a sample of food “packages” sorted by protein content, alongside a range of components that come with it.
To call out a few examples:
- A 4-ounce broiled sirloin steak is a great source of protein—about 33 grams worth. But it also delivers about 5 grams of saturated fat.
- A 4-ounce ham steak with 22 grams of protein has only 1.6 grams of saturated fat, but it’s loaded with 1,500 milligrams worth of sodium.
- 4 ounces of grilled sockeye salmon has about 30 grams of protein, naturally low in sodium, and contains just over 1 gram of saturated fat. Salmon and other fatty fish are also excellent sources of omega-3 fats, a type of fat that’s especially good for the heart.
- A cup of cooked lentils provides about 18 grams of protein and 15 grams of fiber, and it has virtually no saturated fat or sodium.
Research on Protein and Health
Available evidence indicates that it’s the source of protein (or, the protein “package”), rather than the amount of protein, that likely makes a difference for our health. You can explore the research related to each disease in the tabs below, but here’s the evidence-based takeaway: eating healthy protein sources like beans, nuts, fish, or poultry in place of red meat and processed meat can lower the risk of several diseases and premature death.
Research conducted at the Harvard Chan School of Public Health has found that eating even small amounts of red meat—especially processed red meat—on a regular basis is linked to an increased risk of heart disease and stroke, and the risk of dying from cardiovascular disease or any other cause. [4-6] Conversely, replacing red and processed red meat with healthy protein sources such as beans, soy foods, nuts, fish, or poultry seems to reduce these risks. One of the reasons why plant sources of protein are related to lower risk of cardiovascular disease compared to protein from red meat and dairy is because of the different types of fat in these protein packages. Plant-based protein sources are more unsaturated, which lowers LDL cholesterol—an established risk factor for heart disease. Also, plant sources contain no cholesterol. Other factors are likely to contribute to the lower risk, but this is a key factor.
- One investigation followed 120,000 men and women in the Nurses’ Health Study and Health Professionals Follow-Up Study for more than two decades. For every additional 3-ounce serving of unprocessed red meat the study participants consumed each day, their risk of dying from cardiovascular disease increased by 13%. 
- Processed red meat was even more strongly linked to dying from cardiovascular disease—and in smaller amounts: every additional 1.5 ounce serving of processed red meat consumed each day (equivalent to one hot dog or two strips of bacon) was linked to a 20% increase in the risk of cardiovascular disease death.
- Cutting back on red meat could save lives: the researchers estimated that if all the men and women in the study had reduced their total red and processed red meat intake to less than half a serving a day, one in ten cardiovascular disease deaths would have been prevented.
- Another study—the first meta-analysis of randomized controlled trials looking at the health effects of red meat by substituting it for other specific types of foods—found that diets that replaced red meat with healthy plant proteins led to decreases in risk factors for cardiovascular disease. 
- The study included data from 36 randomized controlled trials involving 1,803 participants. The researchers compared people who ate diets with red meat with people who ate more of other types of foods (i.e. chicken, fish, carbohydrates, or plant proteins such as legumes, soy, or nuts), looking at blood concentrations of cholesterol, triglycerides, lipoproteins, and blood pressure—all risk factors for cardiovascular disease.
- Researchers found that when diets with red meat were compared with all other types of diets combined, there were no significant differences in total cholesterol, lipoproteins, or blood pressure, although diets higher in red meat did lead to higher triglyceride concentrations than the comparison diets.
- However, researchers found that diets higher in high-quality plant protein sources such as legumes, soy, and nuts resulted in lower levels of both total and LDL (“bad”) cholesterol compared to diets with red meat.
In terms of the amount of protein consumed, there’s evidence that eating a relatively high-protein diet may be beneficial for the heart, as long as the protein comes from a healthy source.
- A 20-year prospective study of over 80,000 women found that those who ate low-carbohydrate diets that were high in plant-based sources of fat and protein had a 30%lower risk of heart disease compared with women who ate high-carbohydrate, low-fat diets.  However, eating a low-carbohydrate diet high in animal fat or protein did not offer such protection.
- Further evidence of the heart benefits of eating healthy protein in place of carbohydrate comes from a randomized trial known as the Optimal Macronutrient Intake Trial for Heart Health (OmniHeart). A healthy diet that replaced some carbohydrate with healthy protein (or healthy fat) did a better job of lowering blood pressure and harmful low-density lipoprotein (LDL) cholesterol than a higher carbohydrate diet. 
- Similarly, the “EcoAtkins” weight loss trial compared a low-fat, high -carbohydrate, vegetarian diet to a low-carbohydrate vegan diet that was high in vegetable protein and fat. Though weight loss was similar on the two diets, study participants on the high protein diet saw improvements in blood lipids and blood pressure. 
- Of course, occasionally a study will generate headlines because it found the opposite result. For example, one study of Swedish women who ate low-carbohydrate, high-protein diets had higher rates of cardiovascular disease and death than those who ate lower-protein, higher-carbohydrate diets.  But the study, which assessed the women’s diets only once and then followed them for 15 years, did not look at what types of carbohydrates or what sources of protein these women ate. That was important because most of the women’s protein came from animal sources.
Again, the source of protein matters more than protein quantity when it comes to diabetes risk. Eating more red meat predicts a higher risk of type 2 diabetes, while consuming nuts, legumes, and poultry is related to lower risk.
- A 2011 study found that people who ate diets high in red meat, especially processed red meat, had a higher risk of type 2 diabetes than those who rarely ate red or processed meat.  For each additional serving a day of red meat or processed red meat that study participants ate, their risk of diabetes rose 12% and 32%, respectively. Investigators also found that replacing a serving of red meat with one serving of nuts, low-fat dairy products, or whole grains each day was associated with an estimated 16% to 35% lower risk of type 2 diabetes.
- A related study also found that people who started eating more red meat than usual were had a 50% higher risk of developing type 2 diabetes during the next four years, and researchers also found that those who reduced red meat consumption had a 14% lower risk of type 2 diabetes over a 10-year follow-up period.  . In a study that tracked the health of over 289,000 men and women, researchers found that individuals who most frequently ate red meats and chicken cooked at high temperatures were 1.5 times more likely to develop type 2 diabetes, compared to those who ate the least. There was also an increased risk of weight gain and developing obesity in the frequent users of high-temperature cooking methods, which may have contributed to the development of diabetes. Of note, this research demonstrated that cooking methods might contribute to diabetes risk beyond the effects of meat consumption alone.  Learn more about this study.
- More evidence that the source of protein matters comes from a 20-year study that looked at the relationship between low-carbohydrate diets and type 2 diabetes in women. Low-carbohydrate diets that were high in vegetable sources of fat and protein were associated with a lower risk of type 2 diabetes.  But low-carbohydrate diets that were high in animal sources of protein or fat did not show this benefit.
- For type 1 diabetes (formerly called juvenile or insulin-dependent diabetes), proteins found in cow’s milk have been implicated in the development of the disease in babies with a predisposition to the disease, but research remains inconclusive. [16,17]
When it comes to cancer, once again, the source of protein seems to matter more than quantity.
- In the Nurse’s Health Study and the Health Professionals Follow-Up Study, every additional serving per day of red meat or processed red meat was associated with a 10% and 16% higher risk of cancer death, respectively. 
- In October 2015, the World Health Organization (WHO)’s International Agency for Research on Cancer (IARC) concluded that consumption of processed meat is “carcinogenic to humans,” and that consumption of red meat is “probably carcinogenic to humans.”  The IARC Working Group (comprised of 22 scientists from ten countries) reached these conclusions from an evaluation of over 800 studies.
- Conclusions were primarily based on the evidence for colorectal cancer. Data also showed positive associations between processed meat consumption and stomach cancer, and between red meat consumption and pancreatic and prostate cancer.
- In 2016, researchers reviewed protein intakes of more than 131,000 women and men from the Nurses’ Health Study and Health Professionals Follow-up Study. After tracking their diets for up to 32 years, the authors found that a higher intake of red meat, especially processed versions (sausage, bacon, hot dogs, salami), was linked to a modestly higher risk of death, while a higher protein intake from plant foods carried a lower risk. Learn more about this study.
- Digesting protein releases acids into the bloodstream, which the body usually neutralizes with calcium and other buffering agents. As a result, early research theorized that eating lots of protein requires a lot more calcium – which may be pulled from bone. A 2009 systematic review found that this doesn’t appear to happen. 
The same healthy protein foods that are good choices for disease prevention may also help with weight control. Again, it’s the source of protein that matters.
- Researchers at the Harvard Chan School of Public Health followed the diet and lifestyle habits of over 120,000 men and women for up to 20 years, looking at how small changes contributed to weight gain over time. 
- Those who ate more red and processed meat over the course of the study gained more weight, about one extra pound every four years, while those who ate more nuts over the course of the study gained less weight, about a half pound less every four years.
There’s no need to go overboard on protein. Though some studies show benefits of high-protein, low-carbohydrate diets in the short term (such as the paleo diet), avoiding fruits and whole grains means missing out on healthful fiber, vitamins, minerals, and other phytonutrients.
- Specific proteins in food and the environment are involved in food allergies, which are overreactions of the immune system (take gluten and celiac disease, for example).
- Medical journals are also full of reports linking allergic responses to specific protein sources with a variety of conditions (breathing problems, chronic digestive issues, etc.). Eggs, fish, milk, peanuts, tree nuts, and soybeans cause allergic reactions in some people.
- Individuals diagnosed with certain diseases (such as kidney and liver disease) need to monitor their protein intake according to their physician’s guidelines.
- You may have also heard that the use of antibiotics in the production of animal-based foods has contributed to the emergence of “superbugs,” or strains of bacteria resistant to currently available antibiotics. In 2016, the FDA announced a voluntary program to limit the routine use of antibiotics in food production (such as giving antibiotics to healthy animals to help them grow faster).  As a consumer, you may want to find products “raised without antibiotics” if you plan on eating meat. Some companies feature this language on the packaging, others don’t.
Protein Foods and the Planet
Source: World Resources Institute, www.wri.org/proteinscorecard
To give you an idea, this “scorecard” from the World Resources Institute illustrates the differing GHG emissions per gram of protein from both animal and plant-based protein foods.  Making just one pound (454 grams) of lamb generates five times more GHGs than making a pound of chicken and around 30 times more than making a pound of lentils.  In the U.S. alone, beef accounts for 36% of all food-related GHG emissions.  Beyond emissions, it’s also important to note that food production places an enormous demand upon our natural resources, as agriculture is a major contributor to deforestation, species extinction, and freshwater depletion and contamination.
The Bottom Line
Protein is a key part of any diet. The average person needs about 7 grams of protein every day for every 20 pounds of body weight. Because protein is found in an abundance of foods, many people can easily meet this goal. However, not all protein “packages” are created equal. Because foods contain a lot more than protein, it’s important to pay attention to what else is coming with it. That’s why the Healthy Eating Plate encourages choosing healthy protein foods.
Building off this general guidance, here are some additional details and tips for shaping your diet with the best protein choices:
- Get your protein from plants when possible. Eating legumes (beans and peas), nuts, seeds, whole grains, and other plant-based sources of protein is a win for your health and the health of the planet. If most of your protein comes from plants, make sure that you mix up your sources so no “essential” components of protein are missing. The good news is that the plant kingdom offers plenty of options to mix and match. Here are some examples for each category:
- Legumes:lentils, beans (adzuki, black, fava, chickpeas/garbanzo, kidney, lima, mung, pinto etc.), peas (green, snow, snap, split, etc.), edamame/soybeans (and products made from soy: tofu, tempeh, etc.), peanuts.
- Nuts and Seeds:almonds, pistachios, cashews, walnuts, hazelnuts, pecans, hemp seeds, squash and pumpkin seeds, sunflower seeds, flax seeds, sesame seeds, chia seeds.
- Whole Grains: kamut, teff, wheat, quinoa, rice, wild rice, millet, oats, buckwheat,
- Other: while many vegetables and fruits contain some level of protein, it’s generally in smaller amounts than the other plant-based foods. Some examples with higher protein quantities include corn, broccoli, asparagus, brussels sprouts, and artichokes.
Prioritize hearty and savory plant-based preparations
- Upgrade your sources of animal protein. Considering the protein package is particularly important when it comes to animal-based foods:
- Generally, poultry (chicken, turkey, duck) and a variety of seafood (fish, crustaceans, mollusks) are your best bet. Eggs can be a good choice, too.
- If you enjoy dairy foods, it’s best to do so in moderation (think closer to 1-2 servings a day and incorporating yogurt is probably a better choice than getting all your servings from milk or cheese).
- Red meat—which includes unprocessed beef, pork, lamb, veal, mutton, and goat meat—should be consumed on a more limited basis. If you enjoy red meat, consider eating it in small amounts or only on special occasions.
- Processed meats, such as bacon, hot dogs, sausages, and cold cuts should be avoided. Although these products are often made from red meats, processed meats also include items like turkey bacon, chicken sausage, and deli-sliced chicken and ham. (Processed meat refers to any meat that has been “transformed through salting, curing, fermentation, smoking, or other processes to enhance flavor or improve preservation.” )
Looking to reduce red and processed meats, but unsure where to start? Here are a few approaches to cutting-back while keeping your meals satiating and flavorful. Simply find your “starting point” and move forward with the strategies that work for you:
Eat a little less red meat, any way you can
Swap out red meat for healthier meats
Consume less meat, enjoy more variety
Test your protein knowledge!
Ready to see how much you know about protein and healthy protein foods? Try this 10 question quiz to find out:
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- Pan A, Sun Q, Bernstein AM, Manson JE, Willett WC, Hu FB. Changes in red meat consumption and subsequent risk of type 2 diabetes mellitus: three cohorts of US men and women.JAMA internal medicine. 2013 Jul 22173(14):1328-35.
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- Smith JD, Hou T, Ludwig DS, Rimm EB, Willett W, Hu FB, Mozaffarian D. Changes in intake of protein foods, carbohydrate amount and quality, and long-term weight change: results from 3 prospective cohorts–. The American journal of clinical nutrition. 2015 Apr 8101(6):1216-24.
- Li SS, Kendall CW, de Souza RJ, Jayalath VH, Cozma AI, Ha V, Mirrahimi A, Chiavaroli L, Augustin LS, Blanco Mejia S, Leiter LA. Dietary pulses, satiety and food intake: A systematic review and meta‐analysis of acute feeding trials. Obesity. 2014 Aug22(8):1773-80.
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- Guasch-Ferré M, Satija A, Blondin S, Janiszewski M, Emlen E, O’Connor L, Campbell W, Hu F, Willett W, Stampfer M. Meta-Analysis of Randomized Controlled Trials of Red Meat Consumption in Comparison With Various Comparison Diets on Cardiovascular Risk Factors. Circulation. 2019 Apr 1139(15):1828-45.
*Disclosures: Dr. Hu has received research support from the California Walnut Commission. Dr. Campbell reported receiving research support from the National Institutes of Health (T32 Fellowship for Lauren O’Connor), the American Egg Board – The Egg Nutrition Center, The Beef Checkoff Program, The National Dairy Council, The Pork Checkoff Program, and the Barilla Group. Dr. Campbell also reported serving on the 2015 Dietary Guidelines Advisory Committee. Dr. Satija is an employee of Analysis Group, Inc. The other authors declare no conflicts.
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