Valine

Valine is a nutrient belonging to the branch-chained essential amino acid (BCAAs) class.

Valine is also known as Val, 2-Amino-3-methylbutanoic acid and L-valine.

Valine is necessary for immunological function, blood sugar homeostasis, neurotransmitter synthesis, muscle development, energy generation during exercise, and maintaining the body's nitrogen balance.

Valine deficiency can lead to Valinemia. It is a rare metabolic condition characterised by low levels of the enzyme valine transaminase, which is essential for the body to break down (metabolise) valine and may include symptoms like loss of appetite, excessive drowsiness, poor growth, neurological issues, developmental delays, lack of muscle tone, and elevated levels of valine in the blood & urine.

Valine can be obtained naturally in various protein-rich meals derived from plant and animal sources. Plant sources include beans (navy beans, kidney beans, adzuki beans, chickpeas and lentils), mushrooms, gluten-free whole grains (quinoa and brown rice) and seeds (pistachios, cashews and almonds). In contrast, red meat (lamb and beef), fish, poultry (Turkey and chicken), eggs and dairy products (cheese and yoghurt) are excellent sources of animal sources of valine.

Valine is absorbed in the small intestine, transported to tissues like muscles, and then metabolised for energy or protein synthesis. For optimal metabolic equilibrium, excess valine is removed by the kidneys through urine.

The common side effects of valine include digestive discomfort, nausea, and an upset stomach.

Valine is available in tablets, capsules and oral powders.

Biochemical action of Valine

Valine, belonging to the essential amino acid class, acts in several physiological processes. It works via the propionyl-CoA synthesis pathway.

Leucine, isoleucine, and valine are three essential amino acids, referred to as branched-chain amino acids (BCAAs), and they are needed for human nutrition. The health of muscles and energy metabolism benefit greatly from BCAAs.

All three BCAAs undergo catabolism (decomposition), which starts in muscle tissue and results in the synthesis of NADH and FADH2, essential for producing ATP, the body's energy. Each BCAA forms a distinct alpha-keto acid due to a transamination process involving a BCAA aminotransferase and alpha-ketoglutarate. The branched-chain alpha-keto acid dehydrogenase complex is then used to change these alpha-keto acids into the corresponding CoA derivatives. The metabolic pathways vary after this, though. The metabolic route for valine produces propionyl-CoA, a precursor for gluconeogenesis, the process of making glucose.

In general, the catabolism of valine contributes to both the synthesis of glucose and energy production.

Valine is available in tablets, capsules and oral powders.

• Tablets: To be swallowed whole with water/liquid, as applicable.
• Capsules: To be swallowed whole with water/liquid, as applicable.
• Powders, oral: Powders must be mixed thoroughly with the appropriate amount of liquid and stirred well to dissolve the powder, as applicable.

Valine can be used as a supplement when the amount of valine taken through diet is insufficient.

Taking valine supplements effectively treats valine deficiency caused by specific genetic diseases or other disorders.

Valine supplements help in reducing post-workout soreness and accelerating muscle repair.

Supplements containing valine may contribute to energy production during intense physical activities.

Valine supplement may help treat brain trauma as it can improve cognitive functioning.

Vitamins and natural supplements should not replace a balanced diet.

This product is not intended to diagnose, treat or prevent any disease(s).

Valine can help to support as a supplement for the following health benefits:

• Athletic Performance: The main benefit of valine is that it helps build powerful muscles. It increases the production of protein, which is vital for the development of muscles. Participants in one trial who took valine together with Leucine and isoleucine produced an incredible 22% more muscle protein than those who took a placebo. The ability to synthesise muscle protein was considerably more significant when a supplement containing all nine necessary amino acids was used.
• Muscle recovery: A valine supplement can help repair muscle and relieve post-workout discomfort. Soreness is often felt the day after working out, but it can continue for up to three days due to small muscle rips from intense workouts. Valine can lessen soreness intensity and length by decreasing protein synthesis during exercise and lowering creatine kinase levels, an enzyme linked to muscle injury.
• Maintaining of muscles: The body's muscles endure an ongoing breakdown and regeneration process. The equilibrium between protein production and destruction governs muscle protein levels. Muscle wasting occurs when breakdown outpaces repair in conditions including hunger, sickness, fasting, and ageing. However, studies show that valine, frequently present in BCAA supplements, could lower the rate of breakdown of muscles. The process of muscle wasting may be slowed or stopped by taking valine or BCAA supplements, promoting muscle health and maintenance.
• Cirrhosis: Individuals with cirrhosis, a disorder characterised by liver damage and reduced function, may benefit from valine supplementation. Complications from liver illness, such as protein imbalance and muscle loss, are frequently caused by liver disease. Branch-chain amino acids like valine may help in protein synthesis and muscle repair. While further study is required, valine's ability to help people with cirrhosis prevent muscle atrophy shows its potential as a dietary supplement to enhance their physical and mental well-being.
• Gallbladder: For people with gallbladder disease, valine supplements may be beneficial. Problems with the gall bladder can interfere with nutrition absorption and digestion. Valine is a branched-chain amino acid that may benefit digestive health by encouraging the production of proteins and enzymes that help digestion. Further research is required to determine valine's potential benefit to digestion, which could be helpful to people who have gallbladder problems.

Valine supplementation may be administered orally.

Orally: Valine supplements are available as tablets, capsules and powders that can be taken orally. Valine supplements should be taken between meals that include other amino acids to ensure optimal absorption and utilization. Valine supplements should also be taken before bed to promote overnight muscle repair and development.

Taking it before, during or after exercise may boost its impact on growth hormone release for goals associated with activity.

The dosage and duration of treatment should be as per the clinical judgment of the treating healthcare professional).

Vitamins and natural supplements should not replace a balanced diet

This product is not intended to diagnose, treat or prevent any disease(s).

• Tablets: 450 mg, 1000 mg
• Capsules: 400 mg, 450 mg, 800 mg
• Powder, oral: 2000 mg, 150g, 454 g

Dosage Adjustment for Adult Patients

By mouth

Take 1000-2000 mg (or 1/2 tsp) once or twice a day as a dietary supplement, depending on the requirements or as recommended by the physician.

Valine supplements are available in tablets, capsules and oral powders.

Valine should be a supplement that helps in several physiological processes and appropriate dietary restrictions.

• Avoid alcoholic beverages.
• Stay within your daily calorie needs.
• Since these may hinder absorption, keep away from food, especially foods high in other branched-chain amino acids (BCAAs) like Leucine and isoleucine.
• While taking valine supplements, limit the consumption of valine-rich foods to avoid excessive intake.

Recommended Daily Allowance (RDA)

As per FSSAI, the estimated RDA of valine is 26 mg/kg body weight per day.

Upper Tolerable Intake (UTL):

The UTL of valine is not established.

Valine supplementation may be contraindicated in the following conditions:

• Hypersensitivity: sensitive to valine-related allergy.
• Chronic liver disease
• Chronic kidney disease (CKD)
• Kidney failure
• Maple syrup urine disease (a rare, inherited disorder).
• Amino acids disorders
• Pregnancy
• Breastfeeding

Valine supplements should be avoided in pregnant and breastfeeding mothers unless advised to do so by a healthcare professional.

Before taking valine, individuals with renal or liver disorders should see a physician since the dosage may need to be adjusted to prevent adverse effects.

Supplements containing valine should be given cautiously to people with preexisting medical conditions or taking medications.

Individuals with a history of allergies or sensitivities to amino acids should be vigilant and used cautiously.

To avoid potential interactions, it is recommended to use only one amino acid supplement or dietary supplements.

Caution is advised when consuming alcohol with valine.

Avoid the use of valine during breastfeeding.

Avoid the use of valine during pregnancy.

While taking valine supplements, limit the consumption of valine or other branched-chain amino acids (BCAAs) like Leucine and isoleucine to avoid excessive intake.

The adverse reactions related to valine can be categorised as:

• Common: GI disturbances like nausea or stomach upset
• Less common: Headaches and changes in blood sugar levels.
• Rare: Allergic Reactions (Skin rashes, itching, or swelling) and decreased liver or kidney function.

The clinically relevant drug interactions of valine are summarized here:

• Anti-diabetic drugs: Valine has the potential to reduce blood sugar levels. When taken with insulin or other diabetes treatments, this can result in deficient blood sugar levels.
• Antiparkinson’s medications: These medications, such as levodopa, when used along with valine, may interfere with levodopa absorption, reducing its effectiveness.

The common side of Valine include the following:

• Nausea
• vomiting
• Diarrhea
• Stomach bloating
• Fatigue
• Need for coordination.
• Upset stomach

Valine should be prudent in the following group of special populations.

• Pregnancy:

Without specific health recommendations, valine supplements are typically not advised for children. There is no sufficient scientific evidence traceable regarding the use and safety of valine for pregnant populations. Avoid valine supplements unless advised by a healthcare professional while pregnant.

• Paediatrics:

Valine intake is vital for infants as they require more protein and amino acids for healthy development. According to paediatricians, children with certain medical disorders that impact the metabolism of amino acids or the utilisation of protein may benefit from valine supplementation. However, considering that consuming too much valine has the potential to have adverse effects, any supplementation should be done under the supervision of a healthcare professional.

Dosage Adjustment for Paediatric Patients

There are no specific dosage adjustments provided.

• Geriatrics:

Valine helps protein synthesis, essential for preserving muscle mass and the body's composition. The risk of muscle loss (sarcopenia) increases with age. Along with vital minerals, enough valine consumption can stop muscle deterioration. However, since consuming too much valine has the potential to have negative consequences, any supplementation should be done under the supervision of a physician.

• Lactating mothers:

Valine supplements are typically only advised for lactating mothers with specific health recommendations. There is no sufficient scientific evidence traceable regarding the use and safety of valine for lactating mothers populations. Avoid valine supplements unless advised by a healthcare professional while lactating.

Dosage Adjustment in Kidney Impairment

There are no specific dosage adjustments provided.

Dosage Adjustment in Hepatic Impairment

There are no specific dosage adjustments provided.

The physician should be vigilant about the knowledge about identifying and treating overdosage of valine. Overconsumption of valine could lead to symptoms like nausea, vomiting, diarrhoea and difficulty breathing.

There is no specific antidote or treatment for excessive intake of supplemental valine.

Biochemistry profile of Valine

Valine is an α-amino acid with a side chain comprised of straight hydrocarbons. It has a central carbon atom attached to an amino group, a carboxyl group, and a side chain of three carbon atoms.

One of the essential branched-chain amino acids (BCAAs) that the body cannot produce on its own and must obtain from the diet is valine. It greatly aids in preserving muscle tissue and general body composition and acts as an essential component for synthesising new proteins. Transamination, where valine is changed into -ketoisovalerate, signifies the start of valine's catabolism. To generate is butyryl-CoA, a precursor to acetyl-CoA, this -ketoisovalerate then goes through decarboxylation and hydrolysis. The citric acid cycle and oxidative phosphorylation are the final energy sources. Because propionyl-CoA, which valine may be converted into, can enter the gluconeogenic pathway, it also contributes to glucose production. Valine is also involved in producing neurotransmitters and a few other metabolites, which support cognitive and other metabolic functions.

Kinetic profile:

• Absorption: Valine is absorbed from the small intestine by a sodium-dependent active transport process, where it is then circulated throughout the body to different tissues.
• Distribution: Valine is transported by the bloodstream throughout the body after absorption, especially in the skeletal muscles.
• Metabolism: Valine goes through metabolic processes once within cells. It may be broken down into intermediates that can enter the citric acid cycle to produce energy through the catabolic process, which includes converting valine. In addition, especially during times of fasting or low carbohydrate consumption, valine can help with the gluconeogenesis process, which allows the body to produce glucose.
• Elimination: Renal excretion is the main route by which valine and its metabolites are removed from the body. The kidneys filter any excess valine or its metabolites that are not required for various metabolic activities and eliminate them through the urine.

1.https://www.fssai.gov.in/upload/advisories/2021/07/60f1798019f94Direction_RDA_16_07_2021.pdf

2. National Institute of Nutrition. 2011. Dietary guidelines for Indians; 2nd Edition. Hyderabad. India

3. Tessari P. 2019. Nonessential amino acid usage for protein replenishment in humans: a method of estimation; American Society for Nutrition. Department of Medicine, University of Padova, Padova, Italy