Isoleucine (Ile, I)

A balanced, plant-based diet with few to no industrially processed foods generally provides sufficient macro- and micronutrients, with the exception of vitamin B₁₂. However, phytochemicals are particularly relevant for maintaining health and healing, even though they are not considered essential nutrients – apart from vitamins.

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Definition

Isoleucine (Ile, I) is one of eight (ten in children, including histidine and arginine) amino acids considered essential (non-dispensable) for the human body. Humans use 21 proteinogenic amino acids. These are the building blocks of proteins. With the exception of two (lysine and threonine), the body can adapt proteins to its needs, even though eight are classically considered essential.

Occurrence

Legumes, nuts and seeds are particularly rich in isoleucine.

Other beans include kidney beans (1000 mg/100 g) and white beans (1000 mg/100 g). Nuts, seeds, and kernels include sunflower seeds (1100 mg/100 g), cashews (790 mg/100 g), sesame seeds (760 mg/100 g), almonds (750 mg/100 g), walnuts (620 mg/100 g), amaranth (580 mg/100 g), spelt (550 mg/100 g), buckwheat (500 mg/100 g), quinoa (500 mg/100 g), and corn (340 mg/100 g). There are other foods with even higher amounts of this amino acid.¹

Some major sources of isoleucine, such as spirulina (3200 mg), dried parsley (1500 mg, fresh 120 mg), mustard powder (1200 mg), fenugreek (1200 mg), and black mustard (1100 mg), as well as many spices, are consumed in insufficient quantities. Therefore, we have not included them in the table. Soybeans and lupin flour contain about twice the amount of isoleucine as beef (967 mg) and significantly more than chicken breast (1219 mg). Eggs contain 672 mg and cow's milk 198 mg, which corresponds to approximately 10% and only about 10 %, respectively, of the content of soy or lupin flour.¹

A vegan would have to eat a very unbalanced diet to suffer from a persistent protein deficiency.

Storage and Preparation Losses

Heating food denatures proteins, thus altering their properties. A fried egg is one example; it denatures due to the heat in the pan. When an egg is heated, the liquid yolk and the egg white, the main protein source, solidify. The proteins in the egg thicken, a process known as "coagulation" or "flocculation". The egg white coagulates at 60 °C, the yolk at 65 °C, and complete coagulation occurs at 70 °C.

The oxidation of an amino acid by reactive oxygen species can significantly affect its function.

Nutrition - Health

Branched-chain amino acids (BCAAs), consisting of leucine, isoleucine, and valine, are essential amino acids. They play an important role in various bodily processes, such as regulating energy metabolism, gut health, immunity, and disease in both humans and animals.⁹

Our bodies cannot produce (synthesize) BCAAs themselves, but require them in certain amounts to maintain growth and nitrogen balance. Approximately 35% of essential muscle proteins and 40 % of all amino acids required by mammals consist of these BCAAs.^10,11

It is now known that the body irreversibly transaminates only lysine and threonine, and that only these two are truly essential. Specific dietary habits, such as those of fruitarians (fruitarians, fructarians, fruganians) or the 80/10/10 (high-carb) diet, and even more extreme diets, can lead to deficiencies over time. This often occurs over a long period without any directly noticeable symptoms.

Long-term daily requirement

Estimates of the daily requirement for isoleucine in healthy adults range from 7.5 to 28 mg of isoleucine per kilogram of body weight, depending on the method used. The WHO specifies a daily requirement of 20 mg/kg body weight.⁶ However, according to scientific tables Geigy, Vol. 2, p. 232, the minimum requirement for isoleucine, including a 30 % allowance for individual variations, is only 12 mg/kg body weight. This would be 0,9 g/day for a person weighing 75 kg.

The German Federal Institute for Risk Assessment (BfR) states that adults can tolerate up to 2,2 g of isolated isoleucine (alone or in combination) per day in addition to normal food intake. Current study results also suggest that branched-chain amino acids should not be taken individually, but rather in combination. Furthermore, the BfR recommends that children, adolescents, pregnant women, and breastfeeding mothers avoid isolated intakes of branched-chain amino acids from dietary supplements or sports nutrition products.¹²

Deficiency symptoms

A deficiency in isoleucine is possible with insufficient dietary intake over a long period. A natural vegan diet more than adequately covers isoleucine requirements, and increased physical activity naturally leads to increased food intake. Infants are particularly at risk if they are weaned from breast milk too early and receive inappropriate nutrition.

The diseases kwashiorkor and marasmus, which arise from very prolonged protein and general energy deficiency, are now rarely found in the Western world. Milder deficiencies can lead to stunted growth in children and loss of lean body mass in adults.¹¹

A deficiency first manifests itself as a general weakness in physical and mental performance, hormonal fluctuations and susceptibility to illness.

Oversupply

Isoleucine only occurs with high intake of this amino acid. This is hardly possible through diet alone. Therefore, it essentially only affects people who consume isoleucine in isolation via supplements or who overdose on it.

An excess of BCAAs can decrease the uptake of other amino acids, such as phenylalanine, tyrosine, histidine, and tryptophan, which are precursors of dopamine, norepinephrine, histamine, and serotonin, into the brain, because they enter the brain via a common transporter for large neutral amino acids.¹³

In cases of impaired kidney function, a low-protein diet is recommended to prevent increased production and accumulation of urea in the kidneys due to amino acid breakdown. The book * The China Study* vividly illustrates, with strong evidence, that we typically suffer from an excess, not a deficiency, of protein (see detailed book review): Only in recent years have scientists discovered that animal protein, previously considered the highest quality protein (biological value), does not promote optimal health, but rather the opposite.

Functions in the body

Isoleucine contributes to energy production, muscle building, blood sugar regulation, and wound healing.^2,3,4,5

• Isoleucine is of particular importance in the building and protection of muscles.
• During strenuous physical activity, isoleucine can serve as an energy source once the body's free glucose reserves are depleted. This metabolic process leads to gluconeogenesis (new glucose production) via several intermediate steps. The breakdown of isoleucine yields acetyl-CoA and succinyl-CoA. However, even during low-intensity physical activity, an adequate intake of isoleucine is important, as this amino acid is continuously required for the maintenance and regular regeneration of muscle tissue is necessary.
• Isoleucine regulates numerous hormones, including the growth hormone somatotropin and insulin.
• Due to its strengthening effect on the immune system and its contribution to the formation of new tissue, isoleucine plays a crucial role in the defense against pathogens and wound healing.

Absorption and Metabolism

The metabolism of BCAAs occurs in two main steps, which differ in intensity between muscle and liver. In muscle, the first step involves the reversible transamination of BCAAs to the corresponding α-keto acids. For complete breakdown of the BCAAs, the α-keto acids must reach the liver, where they undergo further oxidation.^12,15

In the second step, irreversible oxidative decarboxylation occurs via the branched-chain ketoacid dehydrogenase complex. Enzyme activity is high in the liver, kidneys, and brain in humans, and low in skeletal muscle, intestines, and adipose tissue. Further breakdown of isoleucine yields acetyl-CoA and succinyl-CoA. In this process, isoleucine acts as both a glycogenic and a ketogenic amino acid.

During initial transamination, glutamic acid is formed by the transfer of the nitrogen group to α-ketoglutarate. Besides protein synthesis and serving as an energy substrate, BCAAs act as nitrogen donors in the brain and peripheral tissues. Thus, BCAAs, especially leucine, are important nitrogen sources for the synthesis of the neurotransmitters glutamate and γ-aminobutyric acid in the brain.^12,15

Storage - Consumption - Losses

The main source of BCAAs is the diet, while synthesis by the gut microbiota accounts for only a small portion. BCAAs from food or protein breakdown enter the bloodstream and from there reach the tissues. There, they oxidize or are incorporated into new proteins. The normal value for free isoleucine in the blood is 7 mg/L.

In the human body, isoleucine occurs almost exclusively in a bound state. The isoleucine content is particularly high in muscle tissue. BCAA loss occurs primarily through oxidative degradation. We typically lose 10 to 15 mg of isoleucine per day via urine.^7,16

Structure

Isoleucine is a proteinogenic α-amino acid with a hydrophobic side chain. The term leucine refers to the group of four isomeric amino acids: leucine, isoleucine, tert-leucine, and norleucine.

Other names for isoleucine: α-Amino-β-methylvaleric acid; (2S,3S)-2-Amino-3-methylpentanoic acid. Molecular formula: C₆H₁₃NO₂. Abbreviations: Ile, I (one-letter code).¹⁴