# BIOS Needs Growth

By [ßįôto§hi Nætgœmøto](https://paragraph.com/@to-hi-n-tg-m-to) · 2024-07-19

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> _In the unfolding narrative of human growth, from the delicate beginnings of infancy to the subtle shifts of advanced age, proteins and hormones orchestrate a symphony of development with Insulin-like Growth Factor 1 (IGF-1) as the maestro guiding this complex ballet. This ensemble, comprising the diligent architects of our bodies—proteins—and the subtle conductors of our physiological processes—hormones—plays in harmony to script the saga of the human form across the tapestry of time._

### What is the evolutionary normal human protein intake?

Based on various meat and fish-based models (8), paleolithic ancestors likely consumed between 150 to 200 grams of protein daily, depending on their calorie intake. For instance, with an average intake of 2200 kcal daily, protein consumption would have been closer to 150 grams. While the topic will be further explored in "BIOS Needs Meat," this article focuses on protein levels related to growth.

The evolution of modern humans has spanned various positions on the trophic level. Going from a little meat as primates, to straight-up carnivory with H. erectus and back to generalist levels as H. sapiens with a further decline towards more plant specialists, today, after the agricultural and industrial evolution. According to paleoanthropologist Miki Ben-Dor, the average meat intake for an American (88 grams per day) is still between 100-200% of what is considered "evolutionary normal."

![(9)](https://storage.googleapis.com/papyrus_images/af87831c2db4e1f8e860a9354c164164134ed18a96b2262fbf295955a12f232f.jpg)

(9)

Today's dietary protein recommendations are designed for sedentary individuals. However, following the guidelines for athletes and those engaged in weightlifting, you would be much closer to the evolutionary normal levels.

![From the RDA to evolutionary normal levels, it all makes sense](https://storage.googleapis.com/papyrus_images/5fd4c6538dca5463fde21e7b663b308b75b0a274c416ae8d2546c8fa54c472e9.png)

From the RDA to evolutionary normal levels, it all makes sense

For most of our evolution, human ancestors hunted meat primarily for its fat content as a calorie source, not because of a specific need for high protein intake. Despite some variation, there's a limit to how much protein a human body can utilize effectively. This is because food proteins contain both essential (EAA) and nonessential amino acids (NEAAs), and our body needs to filter out the essential ones and dispose of the excess amounts of both EAAs and NEAAs, and this process creates metabolic waste.

Prey with too little fat and too much lean protein was often avoided, as excessive protein intake is limited by the urea cycle in humans. The human body’s protein intake is rate-limited by its ability to excrete nitrogen waste. Consuming about 31% of total calories from protein (roughly 250 grams) is likely close to the upper limit. Beyond this, there is a risk of illness or protein poisoning. Throughout evolution, our ancestors continually approached this limit, not out of preference for high protein but because animal sources of calories inherently provided substantial protein. In nature, dietary recommendations were unnecessary as their bodies regulated their protein intake.

To understand this limiting mechanism, it’s essential first to grasp the relationship between nitrogen and proteins.

Nitrogen, a colorless, odorless gas that makes up about 78% of the Earth's atmosphere, is crucial for life due to its role in synthesizing proteins and DNA, RNA, and ATP, the fundamental components of all living cells. Through nitrogen fixation, certain bacteria and archaea convert atmospheric nitrogen (N₂) into forms that plants can absorb and use to build amino acids, the building blocks of proteins, and nucleic acids, essential for genetic information storage and transfer.

Unlike these microorganisms, plants and animals cannot directly fix atmospheric nitrogen. Animals obtain nitrogen by consuming plants or other animals, incorporating it into their proteins and DNA. Excess nitrogen is processed in the liver through the urea cycle, converting toxic ammonia into urea, which is then excreted by the kidneys. This intricate interplay of biological processes underscores the nitrogen cycle's critical role in converting and recycling nitrogenous compounds, supporting life across various ecosystems.

Dietary proteins are the primary source of nitrogen for the human body, required for synthesizing our proteins and nucleic acids (DNA and RNA). However, dietary proteins vary in their amino acid composition. Amino acids, the building blocks of proteins, are categorized into essential and non-essential types. Essential amino acids cannot be synthesized by the human body and must be obtained from the diet, whereas non-essential amino acids can be produced by the body to some extent.

When we consume protein, our body breaks it down into individual amino acids. These amino acids are then used to synthesize new proteins as dictated by our DNA, a process needed for growth, repair, and maintaining bodily functions. If the consumed amino acids match the body's current need for protein synthesis, they are efficiently utilized, and the urea cycle's role is minimal in this context.

However, when there's an excess of amino acids, or if they're not in the required types or quantities for immediate protein synthesis, the body needs to manage these surplus amino acids. Non-essential amino acids or excess essential amino acids undergo a process called deamination, where their amino group is removed. This step is needed for two reasons: firstly, it helps convert these amino acids into forms that can be used for energy production or stored as fat. Secondly, the removal of the amino group produces ammonia, a toxic compound that needs to be safely excreted from the body.

The urea cycle comes into play to handle this ammonia. It converts ammonia into urea, a less toxic compound, in the liver, which is then excreted in the urine via the kidneys. This cycle ensures that excess nitrogen from the breakdown of amino acids is safely removed from the body, preventing toxicity. Additionally, some of the carbon skeletons left after deamination can be used to produce energy or synthesize glucose or fats, contributing to the body's energy reserves.

![Net Nitrogen Utilisation](https://storage.googleapis.com/papyrus_images/5e89f55d132a49e3a60b21ea0775fa0c08ba4cee725698994b0eb330f1103e8c.jpg)

Net Nitrogen Utilisation

There's a limit to how much urea the cycle can process at a time. Consuming excessive amounts of protein, beyond what the urea cycle can efficiently handle, leads to an accumulation of ammonia and other nitrogenous wastes in the blood, a condition known as hyperammonemia. This can result in protein poisoning, or "rabbit starvation," where the body cannot expel nitrogen fast enough, leading to symptoms like headache, fatigue, and eventually more serious health issues, including death. This underscores the importance of adhering to protein intake limits.

Furthermore, kidney function tends to decline with age, reducing the ability to efficiently excrete urea and nitrogenous waste, potentially leading to higher levels of these substances in the blood. Blood urea nitrogen (BUN) levels, an indicator of kidney function and protein metabolism, tend to increase with age. Optimal BUN values range between 5 – 15 mg/dL, with levels in this range associated with a decreased risk of all-cause mortality.

Additionally, meat contains sulfuric amino acids, which can lead to chronic metabolic acidosis, a mild form of acidosis that can damage kidney function over time. The kidneys are particularly vulnerable organs, making it crucial to manage protein intake carefully. Although there is nothing harmful about the protein itself to kidney function (in healthy individuals/HMN1), the decline in kidney function is related to mild chronic acidosis and has been shown to be entirely preventable when we buffer urinary Ph to an alkaline state with bicarbonates. On BIOS, you don’t want “low protein”, you want “high protein” with “high bicarbonate” levels, offering the best of both worlds.

Let's return to discussing proteins in the context of their broader impact on health and bodily functions.

![The masterplan](https://storage.googleapis.com/papyrus_images/48233ba89370df13f68f1c1c7a671277f9bd172fefd4e68a09ca22a65d7d6c7d.png)

The masterplan

DNA acts as the master plan for protein synthesis, containing the instructions to build specific proteins through sequences called genes. When the body needs a particular protein, the corresponding gene in the DNA is transcribed into messenger RNA (mRNA), which then travels to a ribosome. There, the mRNA is translated into the amino acid sequence of the protein. Dietary proteins are broken down into amino acids, which the body uses as building blocks to assemble new proteins according to the instructions encoded in the DNA.

As discussed earlier, natural dietary proteins are not perfect. Some amino acids are not in the right type or quantity needed for the body's immediate protein synthesis requirements. The net protein utilization (NPU) is the percentage of ingested nitrogen that is retained in the body for building proteins. NPU is used to determine the nutritional efficiency of dietary proteins, serving as a measure of "protein quality" for human nutrition. Most natural foods have an NPU of around 70-90%, indicating that a significant portion of ingested protein is effectively utilized by the body.

![Egg protein has the highest NPU at 94%](https://storage.googleapis.com/papyrus_images/e6b032a7ee29f7c8bcbc1776f70ddaaf3153b1a00dbe5623518ecdf83e8df2d7.png)

Egg protein has the highest NPU at 94%

Eggs have long been considered the most perfect protein regarding utilization rates. In theory, a perfect protein (NPU of 100%) would be absorbed by the body without any part turning into fuel or fat or causing metabolic waste products. It would stimulate maximum protein synthesis for cell metabolism without contributing direct calories toward energy intake.

### The discovery of a 100% NPU?

In 1998, after 31 years of research, Spanish Professor Dr. Lucà-Moretti discovered that all living organisms, including humans, have their own very specific amino acid formulation, which he called the Master Amino Acid Pattern (MAP). The MAP is a specific formulation of essential amino acids in a pattern purportedly optimized for the highest degree of utilization by the body, with a reported 99% Net Protein Utilization (NPU), which is higher than that of eggs. This means that almost all of the amino acids ingested in this pattern can be used for protein synthesis, with minimal waste or conversion to other compounds that would need to be excreted via the urea cycle.

However, this was not the first instance where protein intake was no longer rate-limited by the urea cycle. Research during World War II laid the groundwork for understanding amino acid utilization. While Moretti might have modified the quantities and conducted randomized controlled trials (RCTs) to develop the MAP, credit for the initial discovery should go to William Cumming Rose, who identified the essential amino acids and their importance in human nutrition.

![The "discovery" of MAP by Dr. Lucà-Moretti](https://storage.googleapis.com/papyrus_images/0fc0c2db4e09fcfce188018a3d457a48a4ab8a8a93091dea183ba8de507ae990.jpg)

The "discovery" of MAP by Dr. Lucà-Moretti

Earlier, in 1931, William Cumming Rose, a former president of the American Society of Biological Chemists, discovered threonine and identified the optimal amino acid composition for rats. During World War II, certain governmental agencies became interested in understanding the amino acid needs of humans. This led to an extensive, long-term research program that lasted until 1955. The research aimed to achieve nitrogen balance and ultimately succeeded, in discovering the amino acid requirements for humans, which are now known as the essential amino acids.

![June 8, 1955](https://storage.googleapis.com/papyrus_images/f7ca8c3ce5cddf8d7d1ef4d407c3d13bd949a12056275d30c8d22c11599b87fa.jpg)

June 8, 1955

Since 1955, the essential amino acids (EAAs) and their ratios have been known and found to be similar to human muscle composition. On the question of how much of this formula we need daily, the researchers concluded that there is significant "biochemical individuality" even among healthy young subjects. It depends on individual factors such as who you are and what you do. Today, a dietary protein is considered “high quality” if it contains a higher proportion of EAAs.

![8 essential amino acids](https://storage.googleapis.com/papyrus_images/a876f2243b948d423028e689016291c26893edf32facc6bfcc08f61712902a3b.jpg)

8 essential amino acids

In the '70s and '80s, the amino acid histidine was recognized as essential for adults, expanding the list of essential amino acids (EAAs) to nine. Initially considered essential only for infants, histidine was so abundant in foods that it was difficult to isolate. Interestingly, when Moretti proposed the Master Amino Acid Pattern (MAP), he used the Rose formula from 40 years earlier, which included only 8 EAAs. By that time, histidine had been recognized as the ninth EAA for 10-20 years.

Some EAA powders today still only include the original 8 EAAs as proposed by Rose. However, most commercial formulations now contain all 9, including histidine. This might not seem spectacular, but thanks to this research, you can now purchase various EAA formulas on the market that include the (upgraded) Rose/MAP formula, containing the essential amino acids in the correct ratio for human needs. This advancement, as Rose might have said, represents "unprecedented times," providing a real privilege for modern nutrition.

![William Cumming Rose](https://storage.googleapis.com/papyrus_images/3420b7e665fe25655526ea573759df42fe4021981f99e26930be28a5619b1197.jpg)

William Cumming Rose

What is not included in the MAP/EAA formula are the non-essential amino acids. These amino acids are classified as non-essential not because they are unimportant, but because our bodies can synthesize them. Their role in supporting both physical and mental health is as important as that of essential amino acids. For instance, proline is vital for promoting collagen production and preventing arterial plaque accumulation. The distinction between essential and non-essential amino acids is often fine and sometimes challenged in the literature. Certain non-essential amino acids can become conditionally essential under specific circumstances, such as wound healing or intense exercise. Be that as it may, only the 9 essential amino acids are required for muscle growth, and adding NEAAs to them doesn’t improve muscle building.

Notably, during the World War II research program led by Rose, researchers decided to incorporate the non-essential amino acid glycine into their formula after observing enhanced growth in rats. This highlighted the importance of even non-essential amino acids in nutritional science. BIOS, for example, reintroduces glycine to the EAAs recognizing its significance.

![9 EAA's, 7 conditionally essential amino acids, 4 NEAA's](https://storage.googleapis.com/papyrus_images/a7de8a63c70f0bcdb7c52c31f5d3bfaad5b4f905f098470de1749d779d8e09a3.png)

9 EAA's, 7 conditionally essential amino acids, 4 NEAA's

![MAP commercial in the 90's... By the time the Master Amino Acid Pattern (MAP) was created, Lucà-Moretti marketed "his" formulation as a superior substitute for traditional protein consumption. It promised optimal protein synthesis rates and offered various benefits, including improved health, longevity, satiety, body weight management, muscle building, and enhanced cardiorespiratory capacity. The MAP formulation aimed to provide an efficient amino acid profile that maximized the body's ability to utilize protein for numerous physiological functions.](https://storage.googleapis.com/papyrus_images/12f0ab71ffd29be2fff05af4187133f2db278695d0da14af34e08d9a6d65e137.jpg)

MAP commercial in the 90's... By the time the Master Amino Acid Pattern (MAP) was created, Lucà-Moretti marketed "his" formulation as a superior substitute for traditional protein consumption. It promised optimal protein synthesis rates and offered various benefits, including improved health, longevity, satiety, body weight management, muscle building, and enhanced cardiorespiratory capacity. The MAP formulation aimed to provide an efficient amino acid profile that maximized the body's ability to utilize protein for numerous physiological functions.

### ROCKET FUEL

The knowledge about Essential Amino Acids (EAAs)(and their ratio), revolutionized dietary approaches by eliminating the need to center diets around protein requirements. Now, a small amount of EAA powder can cover all bases.

EAA supplements are more effective in stimulating muscle protein synthesis (MPS) than an equivalent amount of high-quality protein, whether isolated or part of a meal. According to a 2023 position statement by the ISSN, a 3g oral dose of EAAs can stimulate MPS as much as 20g of whey protein isolate, which typically contains about 10g of EAAs. Adding EAAs to whey protein further enhances the MPS response. This superior effect is due to the higher concentration of EAAs per gram in free-form EAA supplements and their rapid absorption in the intestines, leading to quicker increases in plasma EAA levels and faster peak intramuscular EAA concentrations.

EAA powder supplements are created through chemical synthesis or bacterial fermentation, producing individual amino acids in their free-form state rather than from the enzymatic breakdown of whole proteins. Thus, EAAs do not require digestion to break them down from protein into smaller peptides or amino acids. This allows for rapid absorption into the bloodstream, making them immediately available for protein synthesis and other metabolic processes. This is particularly beneficial for muscle repair and growth immediately after exercise or for treating burn victims in hospitals.

Taking EAAs in supplement form helps build muscle more effectively than consuming protein-rich foods. While scientists agree that the amount of EAAs taken influences muscle building, they are still investigating the precise mechanisms behind this process.

![](https://storage.googleapis.com/papyrus_images/93e272d6df363defd8b43f164b86afb5df900faa5fde806a11d469d90381bcf2.jpg)

The overall effect of a supplement on muscle building throughout the day depends not only on your body's immediate response but also on its reaction to your regular meals. Interestingly, having a protein shake before a meal might reduce the muscle-building benefits of the meal. However, taking a 15-gram dose of EAA supplements doesn't interfere with the muscle-building effects of your meals.

What's remarkable about EAA supplements is their rapid absorption. Since they don't need to be broken down like food protein, they quickly enter your bloodstream. For example, taking 15 grams of EAAs from a supplement can elevate blood amino acid levels much faster and higher than eating a steak, even if the steak contains more protein. This quick increase in blood amino acids is highly beneficial for muscle building. You can take an EAA protein shake before a meal to boost your muscles, then consume the meal as usual and still benefit from its protein content, absorbed more gradually.

EAA supplements offer a way to stimulate muscle protein synthesis and support metabolic functions with minimal caloric intake compared to whole protein sources or other protein powders. This can be particularly advantageous for individuals managing their calorie intake for weight loss or body composition goals. The intake is less bulky compared to either food or normal protein shakes, requiring only a small amount of powder that rapidly dissolves in water.

EAAs can be an essential supplement for those on restricted diets, including vegetarians and vegans, who might find it challenging to obtain all essential amino acids from their diets. Even when they do, plant proteins might be inferior in quality. During periods of caloric deficit, EAA supplementation can help preserve lean muscle mass. EAAs provide the necessary signals for muscle protein synthesis without requiring significant caloric intake, making them ideal for weight loss programs focused on fat loss while preserving muscle.

When we don't eat enough protein during a weight loss diet or fasting, it can affect not just our muscles but our entire body, including other organs and tissues. If our body doesn't get enough essential amino acids (EAAs) from food, it starts breaking down muscle to obtain these nutrients. Additionally, when calorie intake is low, the body might use the protein we eat for energy instead of using it to build and repair muscle. During these conditions, whole-body EAA requirements are raised, meaning EAA supplements solve this issue, while extra protein in other forms might not. Clinical data has proven that these supplements counteract protein disarrangement and preserve energy homeostasis in acute and chronic hypercatabolic conditions without influencing renal function \[14\].

As highlighted before, since EAAs are directly used for protein synthesis, there's less nitrogen waste generated compared to consuming complete proteins that need to be broken down into individual amino acids before they can be used, which can increase BUN levels. The metabolism of amino acids in the liver produces ammonia, which is then converted to urea and contributes to BUN. Consuming free-form EAAs can lead to a more straightforward utilization for protein synthesis, potentially resulting in less ammonia (and consequently urea) needing to be processed and excreted.

EAA supplements, being free-form amino acids, also do not contain purines as found in high-protein foods. This means that they can provide the essential amino acids necessary for various bodily functions, including muscle synthesis and repair, without contributing to the body's uric acid load, which can lead to uric acid-related conditions, such as gout or kidney stones.

While the necessity of obtaining adequate amounts of each EAA through high-quality protein intake has been acknowledged for decades, the specific advantages of consuming free-form EAAs in amounts surpassing these minimal requirements have only been fully recognized recently. The market offers single-free amino acid supplements, such as leucine or lysine, and compositions featuring small groups of EAAs, notably the branched-chain amino acids (BCAAs) - leucine, valine, and isoleucine. However, research indicates that the most significant benefits are derived from supplements containing a complete set of all the EAAs. You want to have all nine essential amino acids in the shake at the same time for muscle synthesis; that’s why BCAA powders are such an overhyped inferior supplement. These only deliver 3 out of 9 EAAs and are an inferior muscle builder.

Dr. Robert Wolfe is another expert who specializes in essential amino acid research. He has 30+ years of clinical research, 500+ peer-reviewed publications, and has been cited over 70,000 times by other researchers. Accumulation of liver fat rises with age, and EAAs have been shown in Wolfe’s research to cut levels of liver fat in half, competing with Fenofibrate (a leading prescription drug for reducing plasma triglyceride levels) which had no effect at all. EAAs also improve blood lipids in patients with hypercholesterolemia, resulting in less cholesterol, LDL, and triglycerides.

According to the 2023 position statement of the International Society of Sports Nutrition, free-form EAA supplementation can support and enhance muscle physiology, crucial not only for athletes looking to improve performance and recovery but also for aging populations and individuals recovering from illness or injury. The ability of EAAs to promote protein synthesis more effectively than dietary protein or supplements with incomplete EAA profiles (all of them really), suggests a targeted approach to nutrition that can support muscle health, improve functional capacity, and potentially contribute to better overall health outcomes.

### Beyond Bricks

Essential amino acids (EAAs) and the Master Amino Acid Pattern (MAP) play roles beyond merely serving as building blocks for tissue construction; they also activate signaling pathways and regulate protein synthesis by triggering gene activation.

Protein synthesis unfolds in two stages: transcription, where DNA is transcribed into messenger RNA (mRNA), and translation, where mRNA is used to assemble proteins in the ribosome with the help of transfer RNA (tRNA). EAAs help during the initiation and elongation phases of this process, especially by activating the mammalian target of rapamycin complex 1 (mTORC1), which is crucial for starting protein synthesis.

Studies have shown that consuming EAAs can significantly enhance muscle protein synthesis even without exercise. Dr. Robert Wolfe's research for NASA demonstrated that muscle mass could be maintained and even increased with EAA supplementation during complete bed rest, which is why EAAs are taken to space due to their efficiency and space-saving properties 【NAG91155】【Paddon-Jones, 2004】.

EAA supplementation has shown remarkable benefits, particularly in older adults. When given EAAs (11g twice daily), they not only gain muscle but also improve in physical activities. Even smaller doses (3g twice a day) have been shown to increase strength and walking speed. In scenarios like hip replacement recovery, EAA supplementation has led to an 800% increase in strength recovery compared to standard care 【12】.

Further research has indicated that EAAs taken immediately after resistance exercise can enhance muscle building and balance as effectively as a full mix of amino acids. The timing of EAA intake post-exercise appears flexible, with the muscle-building effects remaining consistent whether taken immediately or a few hours later. This is particularly beneficial for older adults, where EAAs help increase muscle-building signals and the number of satellite cells involved in muscle repair and growth.

Additionally, EAAs are effective in reducing muscle damage and loss of strength after exercise, contributing to overall recovery. This effect underscores the importance of EAAs in maintaining muscle health and function, not just by boosting muscle protein synthesis but also by aiding in recovery and repair.

Overall, EAAs are powerful agents in promoting muscle growth, strength, and recovery across different age groups and conditions, highlighting their significant role in both the synthesis and regulation of proteins essential for health and physical performance.

### LONGEVITY: EAAs as a calorie restriction mimetic

As we age, many biological functions start to decline, leading to a higher risk of diseases like heart disease, cancer, and diabetes, and ultimately increasing the chance of death. One of the key factors in aging is how our mitochondria, the powerhouses of our cells, start to function poorly. They don't produce energy as well as they used to, and our bodies don't make as many new mitochondria. This, along with more damage from harmful oxygen molecules, plays a big role in the aging process.

However, there are ways to fight some of these aging effects. Cutting back on calories (“calorie restriction, CR”) and regular moderate exercise have been shown to help boost the production of certain proteins in our body that make new mitochondria and protect our cells from damage (at least in the lab). These strategies increase the levels of PGC-1α, which helps make new mitochondria, and SIRT1, which helps protect cells and extend lifespan, thus reducing damage in our tissues. And this can be done with EAAs too (14).

EAAs have shown promise in extending lifespan in yeast studies. Building on this, research (13) has looked into whether a diet supplemented with EAAs could help with aging-related issues in animals and humans. Indeed, supplementing with a mix of EAAs has been found to increase the average lifespan of mice, boost the creation of new mitochondria, activate mTOR/eNOS pathways to benefit cardiovascular and metabolic health, and enhance the expression of SIRT1 in muscle tissues. NO is primarily produced by endothelial NO synthase (eNOS) and is involved in various physiological processes, including mitochondrial biogenesis and angiogenesis.

EAAs also helped upregulate the body's defense system against oxidative damage by activating the master antioxidant switch in the body Nrf2, leading to less damage from oxygen molecules by increasing superoxide dismutase (SOD) and catalase (11)(13)(14). EAA formulations have been shown to enhance ROS scavenging mechanisms and improve mitochondrial function, leading to an overall increase in antioxidant status.

eNOS-PGC-1α-mediated mitochondrial renewal mechanisms are the basis for the benefits of both calorie restriction and exercise and EAAs elicit the same mechanism (14). It looks like I have my second calorie restriction mimetic for BIOS, with alcohol consumption being another powerful tool. (See BIOS Needs Alcohol).

Although cutting calories looks good in animal models, it's not something many people, especially older adults, might want to or be able to stick with. And it might turn out not to be a bright idea too, your body needs protein for the immune system, and the antioxidant system (glutathione levels), but protein is also needed for DNA repair, proper hormone levels, tissue growth, physical functioning, ATP production, prevention of cancer, and maintenance of cardiovascular health. That's where EAA supplements come in as a potential alternative to mimic some of the life-extending benefits of calorie restriction without having the drawbacks. While more research is needed, especially for humans, the findings so far are encouraging for using EAA supplements as a way to improve health with age.

In “BIOS Needs Tryptophan & Indoles”, I already discussed how important and neglected proteolytic fermentation is for the health of the microbiome. 4 out of the 10 most important metabolites circulating in our bodies associated with good health are indoles originating from the metabolism of tryptophan by the microbiome, an essential amino acid. But this is not merely limited to tryptophan, EAAs affect intestinal bacterial growth in a species-specific manner to support microbiota growth and survival, in the same ways that fiber does (14). The gut microbiota catabolizes the amino acids and produces NO from them and short-chain fatty acids like propionate, butyrate, and acetate. EAAs protect the intestinal barrier and mucosal immunity (14) and can reduce bacteria associated with obesity.

In medical settings, supplementing diets with essential amino acids (EAAs) has shown benefits across a wide range of health conditions, many of which are associated with aging. These conditions include muscle loss (sarcopenia), infections acquired in long-term care settings, reduced physical function, and heart failure. EAAs have also helped in situations like rehabilitation after injuries, recovery from strokes, periods of bed rest or immobility, peripheral artery disease, renal failure, inflammation, critical illnesses, lung cancer, cystic fibrosis, chronic obstructive pulmonary disease (COPD), wound healing, brain injury, metabolic syndrome, cardiovascular risk factors, obesity, liver fat issues, and diabetes. As stated by the ISSN, even in the absence of exercise stimulus, EAA administration in anabolically resistant populations, such as aging and pathologies, is beneficial to clinical outcomes and efficacious in the restoration of strength and functional performance.

And still, we are merely scratching the surface here, while amino acids are known to be used for protein synthesis, they are critical for many other cellular processes. They supply intermediates that drive metabolic rewiring upon immune cell activation, and are used to make antioxidants such as glutathione, maintaining redox balance. They provide methyl and acetyl groups to epigenetically modify DNA and histones to facilitate specific gene expression programs in immune cells. These intermediates, and others, can also be used to post-translationally modify proteins and affect their function. Amino acids drive proliferation and growth by fueling nucleotide synthesis and driving translation, and can also be stored in lysosomes, driving autophagy as a protective mechanism in times of stress.

### Growth restriction is like putting a gun to your head

Whether it is the intentional withholding of protein-specific amino acids, or calories through a certain lifestyle or “biohacking” routine, to affect certain cellular pathways in a misguided attempt to extend human longevity, BIOS posits that HMN1 (see Bios Needs Activator X) is an advanced model that displays the strength of the human body and a guaranteed robust expiration date of 70-80 years in nature.

Biological evolution has already perfected the life extension of the so-called third chimpanzee on its own with great results. Scientists are critical of their “anti-aging” colleagues, who try to tamper with cellular pathways that do extend longevity in animal models, but which fail to show results in humans because nature has already optimized the longevity of our species. These attempts can only work counterproductive (don’t try to fix what ain’t broken), BIOS posits that we can only leverage the existing framework.

Growth restriction is akin to self-harm when it involves deliberately inhibiting mTOR, as mTOR is essential for healing processes, including DNA repair. Inhibiting mTOR can lead to the accumulation of DNA double-strand breaks. For instance, rapamycin, an mTOR inhibitor, causes testicular damage, heart scarring, and liver fattening in mice, making them unhealthier despite an increase in lifespan (15, 16).

Uric acid (UA) is a powerful antioxidant and a major plasma antioxidant in humans, generated during purine nucleotide metabolism. It accounts for about 66% of the total oxygen-scavenging activity in the blood serum. UA effectively neutralizes free radicals produced by xanthine oxidase during the catalysis of xanthine and hypoxanthine, offering cellular protection from oxidative damage. The typical blood level of UA in humans ranges from 3.5 to 7.5 mg/dL (21, 22, 23, 24, 25).

So what we don’t want to do on BIOS is substitute EAAs for all daily protein intake, we still want the other protein shakes and whole food protein sources. I suggest a high cysteine protein like native whey or egg white protein and a plant-based hydrolyzed protein, I also like soy protein isolates because they still contain a considerable phytochemical content.

Various dietary foods and medicinal plants rich in vitamins and phytochemicals also provide additional protection against oxidative stress. Key antioxidants include vitamins E, A, and C, flavonoids, carotenoids, lipoic acids, and tannins.

A marginal deficiency in essential amino acids, such as methionine restriction, can lead to hyperphagia (overeating), similar to low-protein diets (17). Supplementing with branched-chain amino acids (BCAAs) can cause imbalances among essential amino acids (EAAs), leading to hyperphagia, obesity, and insulin resistance, and can also result in tryptophan and serotonin depletion (18). This phenomenon, known as 'protein leverage,' indicates that a strong appetite for protein drives the overconsumption of fats and carbohydrates when consuming protein-dilute diets.

Some more evidence for pre-workout EAA being ergogenic by improving the secretion of anabolic hormones, modifying fuel use during exercise, preventing mental fatigue, a reduction of subsequent damage-induced power loss due to increased muscle recovery, and stimulating post-MPS (6).

It has been proven that the requirement of an animal for each amino acid is encoded by its genome. There seems to be a species-specific (genetic) optimal amount of protein for mammals. Hitting this amino acid range will benefit everything in that species including growth, satiation ànd longevity. It's not the lowest amount of protein that is optimal for aging, but the appropriate amount. Looking at our evolutionary baseline and evidence from modern human populations, it’s clear that people are not yet hitting their exome-optimized intake level that would benefit growth _(muscle mass, sports performance, healthy aging)_ and reproduction without cost to lifespan.

Ultimately, an optimal amino acid profile for HMN1 likely matches the mRNA in target tissues. Humans are a long-lived species, and understanding the intricate balance of amino acids, gene expression, and antioxidant mechanisms is key to improving health and longevity.

### Transsulfuration Pathway

Methionine restriction is considered an "anti-aging" strategy because methionine, a sulfur-containing amino acid (like cysteine and taurine), is thought to accelerate aging “in animals”, whereas restricting it has been shown to extend lifespan in these studies.

When methionine is metabolized, it generates homocysteine, which, at high levels, is linked to cardiovascular diseases. Thus, the rationale is that restricting methionine intake can lower homocysteine levels.

The transsulfuration pathway converts homocysteine, a byproduct of methionine metabolism, into cysteine, which is then used to produce glutathione, a major antioxidant. Studies on long-lived populations show increased activity and effectiveness in their transsulfuration pathways. Therefore, rather than reducing methionine intake, enhancing the transsulfuration pathway can better handle methionine, this is what we want for BIOS, sufficient methionine (EAAs, high protein diets), and high transsulfuration.

Methionine, an essential amino acid, offers several health benefits. It is crucial for protein synthesis, supporting tissue growth, repair, and maintenance. Methionine is a precursor to cysteine, necessary for producing glutathione, the body’s main antioxidant. It also aids in methylation processes, DNA synthesis, gene regulation, and detoxification. These are not things, you should be willing to restrict.

Additionally, methionine supports liver health by aiding detoxification and lipid metabolism, helps produce keratin and collagen for healthy skin, hair, and nails, and contributes to mood and cognitive function through synthesizing S-adenosylmethionine (SAMe). It also supports wound healing and immune function.

To enhance the transsulfuration pathway, maintain plentiful methionine intake rather than restricting it. Consider supplementing cysteine (500-1000 mg/day) or consuming native whey or egg white shakes if you eat little meat or dairy. Taurine, another sulfur-containing amino acid, is part of the transsulfuration pathway and has a role in removing toxic byproducts and is in turn associated with increased longevity, consider 500mg/day. Glycine is part of this pathway too, including glycine-rich foods like bone broth, meat, fish, dairy products, and legumes, or taking glycine supplements (3-10 grams daily), can enhance detoxification and promote longevity.

Additionally, ensure sufficient intake of methyl donors like folate (vitamin B9), vitamin B12, and betaine, which maintain proper methylation linked to the transsulfuration pathway. Green leafy vegetables, legumes, whole grains, and animal products are good sources. By following these strategies, you can enhance the effectiveness of your transsulfuration pathway, supporting overall health and longevity.

### DOSING

Consuming Essential Amino Acids (EAAs) typically does not cause adverse effects.

There's limited information to establish a safe upper limit for EAA intake. Available data suggest that consuming over 100 grams of EAAs supplementally per day, on top of an average habitual intake of about 40 grams per day, is safe for American adults. A reasonable dose for an EAA supplement is up to 15 grams, and even taking up to three times this amount daily aligns with the normal EAA intake from dietary proteins.

A dose as small as 1.5g, can stimulate muscle protein synthesis. The maximum effective dose beyond which no increase of MPS takes place is between 15-18g.

Studies have shown that taking EAAs right before or right after lifting weights can boost the levels of amino acids (using phenylalanine as a marker) in both the blood and muscles by 130%. But, the interesting part is that taking EAAs just before working out leads to a much bigger increase in muscle protein building than taking them afterward.

This happens because drinking EAAs before exercising improves how well amino acids are delivered to your muscles, thanks to increased blood flow from the exercise. This means about three times more amino acids get to your muscles, making it easier for them to grow. This fits with other research that says having more EAAs in your system can kickstart muscle and overall protein building in your body. However, not all studies agree on this when carbohydrates are added.

Interestingly, taking another dose of EAAs an hour after the first one seems to keep the muscle-building process going strong, suggesting that the effect of EAAs isn't just a one-time boost but can be sustained with multiple doses.

Regular folks could take 3.6 grams once or twice a day, and 15 grams 2-3x a day as a routine.

### Updated Dosing Recommendations

Scientists (22) are discovering that although EAAs are more effective than regular protein, combining the EAA with whey protein powders can enhance anabolic effects. This may be because whey provides NEAAs, which aren't essential for muscle building but could become limiting factors. Another possibility is the presence of peptides in whey. It could also be that whey has unique properties, such as its cysteine content, its role in insulin regulation, or its ability to activate incretins.

The combination of EAAs and whey protein is more anabolic in older adults (20) and was later found to be equally effective in younger adults (23). A dose of 0.10 g/kg of free-form EAAs is sufficient to maximize muscle protein synthesis under normal conditions, with higher amounts only being relevant when considering total daily protein intake.

The ideal ratio of EAAs to whey can be 1:1. For example, if you weigh 70 kg, you would take 7 g of EAAs combined with 7 g of whey in a shake, at least twice a day. For greater effect, you can double the dose to 28 g and take it twice a day, or triple it to 42 g twice daily for maximum benefit, such as during heavy training or recovery from injury.

If I'm not mistaken, this combination was supposedly used in the Robert Wolfe NASA study where they had people in their beds for 30 days and they came out with more muscle mass.

✅Remember to prioritise morning protein intake and pre-workout EAA intake

✅Take EAAs/protein, 30 minutes before exercise. The increased blood flow during exercise will enhance MPS maximally

✅Take another dose or half dose, an hour after exercise to maintain these MPS levels

✅While EAAs are superior for MPS compared to normal protein, a combination of EAA + whey is even more anabolic. This might be triggered by properties of whey, but it might be relevant to other protein sources too

✅On BIOS, we opt for a 1:1 ratio of EAAs + whey or other protein isolates

✅For a 1:1 EAA-to-whey ratio, take 7 g of each per 70 kg body weight, twice daily. For higher demands (training, recovery), double or triple the dose to 28-42 g, twice a day

✅The EAA + whey combination is especially compensating during dieting and energy restriction where it superiorly balances anabolic activity and burns more adipose tissue as compared to whey alone or carbohydrates because in this condition the EAA needs are further raised (24)

✅For BIOS, we can further bump (21) the superior effects on muscle strength and MPS by opting for native whey instead of regular commercial whey isolates

✅Including whey protein in the morning may enhance the anabolic window, supporting IGF-1 levels and glucose uptake. Opting for native whey offers additional benefits due to its higher cysteine content, which boosts glutathione production, acting as a powerful antioxidant. It also contains immunoglobulins and lactoferrin, supporting immune health. Additionally, the presence of tryptophan in intact alpha-lactalbumin may aid serotonin production, contributing to mood regulation

✅ This all is congruent with previous protein recommendations on BIOS, where after I read a position statement from The Society of Sports Nutrition highlighted that stacking EAAs with a regular protein shake is effective because EAAs are absorbed rapidly. In essence, meaning that athletes can add EAAs to protein shakes as they would have added (inferior) BCAAs in the past.

On BIOS, you can layer EAAs, then hydrolysate or isolate protein, followed by whole-food animal proteins for sustained anabolic support.

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*Originally published on [ßįôto§hi Nætgœmøto](https://paragraph.com/@to-hi-n-tg-m-to/bios-needs-growth)*