Key Takeaways (expand)
- Threonine is one of the nine essential amino acids (meaning we must obtain it from our diet), and one of 20 amino acids that can be used to create protein.
- Many of threonine’s functions are due to its presence as a residue of specific proteins, including collagen, elastin, and enamel.
- It also influences growth and protein synthesis of skeletal muscle, both due to contributing to protein synthesis and due to acting as a signaling molecule within the protein synthesis pathway.
- Threonine is needed for synthesizing mucins—large glycoproteins that help form mucus secretions throughout the body.
- Due to being a component of the intestinal mucus layer, there’s particularly high demand for threonine in the gut.
- Threonine is involved in fat metabolism, and can help prevent fat accumulation in organs like the liver.
- Its role in lipid metabolism makes threonine potentially helpful for fighting metabolic diseases, including cardiovascular disease.
- Threonine plays an important role in gut immune function, and has a synergistic effect with certain carbohydrates (such as pectin) to promote intestinal immune responses.
- Threonine may also help support healthy gut morphology!
- If threonine deficiency occurs, it may impair mucin production in the gut, alter lipid metabolism in the liver (leading to the buildup of liver fat), and increase susceptibility to seizures.
- Due to its effects on collagen and elastin, threonine may help improve
- The best sources of threonine are protein-rich foods like dairy, fish, poultry, meat, eggs, and lentils.
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Threonine (symbol Thr) is one of the nine amino acids that’s essential for humans, meaning we must obtain it from our diet. Of the 20 common amino acids found in proteins, it was the very last to be discovered: the credit here typically goes to American biochemist William Cumming Rose and his colleagues at the University of Illinois (Urbana–Champaign), who discovered it in 1936, although it was reportedly isolated from oat protein a decade earlier by scientists at Imperial College London. This amino acid was named “threonine” due to its similar molecular structure to threonic acid.
Along with being used for protein biosynthesis, threonine promotes fat metabolism, keeps bones and tooth enamel strong, and is involved in liver, intestinal, and immune system function. It’s also important for connective tissue and muscle strength and elasticity, and may even improve wound healing and recovery from injury.
The best sources of threonine are protein-rich foods like dairy, fish, poultry, meat, eggs, and lentils. It’s also found in sesame seeds, mushrooms, and leafy vegetables.
The Biological Roles of Threonine
Broadly, amino acids are molecules with the molecular formula of R-CH(NH2)-COOH-NH2, where -NH2 is the basic amino group, COOH is an acidic carboxyl group, and R represents a molecular unit called a side chain. That side chain is unique for each amino acid, and its chemical properties create different classes of amino acids: nonpolar and neutral, polar and neutral, polar and acidic, and polar and basic.
Although hundreds of amino acids exist, only 20 of them are used for what amino acids are arguably most known for: forming the building blocks of proteins. Proteins are not only an essential macronutrient in the human diet; they’re molecules that perform most of the various functions of life. In addition to being major structural components of cells and tissues, proteins have incredibly diverse roles that range from driving chemical reactions (e.g., enzymes) to signaling (e.g., some types of hormones) to transporting and storing nutrients. Proteins are synthesized within cells through a two-phase process of transcription and translation, during which amino acids get linked together to form long chains (spanning anywhere from 20 to over 2,000 amino acids in length!).
So, while all proteins are made of amino acids, not all amino acids are used for making proteins! We use the term proteinogenic amino acids to refer specifically to the amino acids that get encoded into our DNA and incorporated into proteins. Meanwhile, non-proteinogenic amino acids do neither of these things (although they still have some very important biological roles!).
Amino acids can be further classified based on whether we can create them in our bodies, or need them from our diet. Essential amino acids are amino acids that can only be obtained from foods; these include histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. Non-essential amino acids are amino acids our bodies can synthesize metabolically from other molecules; these include alanine, arginine, asparagine, aspartic acid, cysteine, glutamic acid, glutamine, glycine, proline, serine, and tyrosine. And, some amino acids are conditionally essential, meaning our bodies can normally make them, but some circumstances (like illness or stress) can limit their synthesis and create a dietary requirement. These include arginine, cysteine, glutamine, tyrosine, glycine, ornithine, proline, and serine.
As an essential and proteinogenic amino acid, threonine must be supplied from dietary sources, and is used to synthesize a number of important proteins!
In fact, many of threonine’s functions are due to its presence as a residue of specific proteins, including collagen, elastin, and enamel. This makes it a contributor to dental health, skeletal strength, and connective tissue. It also influences growth and protein synthesis in skeletal muscles—both by serving as a precursor for protein synthesis, and also by acting as a signaling molecule to regulate the protein synthesis pathway.
Threonine is also needed for the synthesis of mucins—large glycoproteins produced by epithelial cells and that help form mucus secretions throughout the body (including the respiratory tract and GI tract). There’s particularly high demand for threonine in the intestine, since threonine is needed for synthesizing the intestinal mucus layer. Threonine availability in the intestinal lumen significantly impacts the mucin production there. Animal studies suggest that the body prioritizes the use of threonine for mucin production so much that in times of nutritional inadequacy, muscle growth and other protein-related tissue functions will be compromised in order to keep threonine available for mucin synthesis!
Threonine plays an important role in the metabolism of fat and porphyrins (important molecules found in hemoglobins, peroxidases, cytochromes, catalases, myoglobins, and more). Threonine is particularly critical for fat metabolism in the liver. Insufficient threonine leads to an increased expression of genes involved in fatty acid and triglyceride synthesis, while downregulating the expression of genes associated with fatty acid and triglyceride transport. So, adequate levels are needed in order to ensure fat is appropriately burned or transported instead of accumulating.
Threonine also plays a role in the immune system—especially gut immune function. In vitro experiments show that lymphocytes use threonine to support their proliferation and antibody secretion, and threonine can influence the secretion of immunoglobin A (IgA) and modulate the expression of inflammatory cytokines in the gut. Animal experiments show that threonine supplementation up-regulates interleukin-6 gene expression and down-regulates the expression of several inflammatory mediators (interferon γ, interleukin-12, and tumor necrosis factor alpha). And in animal models of bacterial infection, threonine deficiency can worsen the intestinal inflammatory response by promoting the gene expression of pro-inflammatory cytokines and inhibiting the expression of anti-inflammatory cytokines.
Interestingly, threonine may have a synergistic effect with fiber and other carbohydrates when it comes to enhancing immune function. Some studies show that threonine and pectin, for example, work together to promote intestinal immune responses during infection!
Although many animals can convert threonine into glycine (another amino acid) via the enzyme L-threonine 3-dehydrogenase, this pathway isn’t very active in humans! Our version of the gene responsible for L-threonine 3-dehydrogenase expression is a pseudogene—that is, a nonfunctional segment of DNA that structurally resembles a gene, but isn’t actually capable of coding for a protein. While animal experiments tend to show substantial degradation of threonine into glycine, similar studies in humans show that only a small amount of threonine gets catabolized through this pathway (and even then, only in the context of a very high protein intake). Because so much of what we know about threonine comes from animal experiments, and because some of the health effects of threonine seen in those studies is due to its conversion to glycine, it’s important to be cautious in how we interpret these findings for humans!
Up to 4 g of threonine daily for a period of one year appears to be safe for most people. Sometimes, minor side effects can occur from from supplementation, including headache, nausea, skin rash, and upset stomach. And, people taking NMDA antagonists (which are often used to treat Alzheimer’s disease) are advised to avoid using threonine supplements.
Threonine in Health and Disease
Threonine has demonstrated a number of interesting health benefits in studies—particularly for fat metabolism, cardiovascular health, gut health, bone health, and wound healing!
Threonine, Obesity, and Lipid Metabolism
Studies suggest that threonine may benefit obesity by promoting fat metabolism, including preventing fat buildup in specific organs (especially the liver) and supporting overall metabolic health. In one experiment of mice with high fat diet-induced obesity, the addition of supplemental threonine led to a significant decrease in body weight, fat pad weights, blood glucose levels, triglyceride levels, LDL and total cholesterol levels, and insulin resistance (as measured by HOMA-IR). From a mechanistic perspective, threonine achieved these effects by down-regulating the expression of genes involved in lipogenesis (the creation of fat) and up-regulating the expression of genes involved in lipolysis (the breakdown of fat), while also stimulating the brown tissue expression of uncoupling protein 1 (UCP-1)—a protein that increases fat burning through thermogenesis. Importantly, the other amino acids tested in this experiment (methionine and lysine) failed to have any significant effect on metabolism. So, threonine appears uniquely suited for inhibiting fat mass and improving lipid metabolism—at least in obese mice! Much more research is needed in humans, however.
Threonine and Cardiovascular Disease
The supportive role threonine plays in lipid metabolism may also make it helpful for fighting metabolic diseases, including cardiovascular disease. A cross-sectional study found that higher plasma levels of threonine were associated with lower levels of small density LDL (a particularly atherogenic form of LDL), triglycerides, and remnant-like particle cholesterol (a stand-alone cardiovascular risk factor). In fact, participants in the highest tertile of plasma threonine had a 56% lower risk of elevated triglycerides and 43% lower risk of elevated small density LDL, compared to those in the lowest tertile of plasma threonine. Although correlation doesn’t prove causation here, these findings do warrant further investigation into a possible protective role of threonine on cardiovascular health!
Threonine and Gut Health
Threonine also appears beneficial for gut health in several different ways. Along with helping maintain the integrity of the intestinal mucosa (by helping form mucin), animal experiments show that threonine supplementation can support healthy gut morphology—including positively affecting crypt depth, villus height, the quantity of goblet cells, and epithelial thickness.
And, when threonine availability is low, animal models show a decline in digestive enzyme synthesis and brush border enzyme activity, suggesting threonine could enhance the digestive and absorptive capacity of the gut. There’s even evidence that threonine can support healthy gut microbiota: animal studies show that high dietary threonine reduces pathogenic Salmonella and E. coli populations, while increasing levels of beneficial Lactobacillus. Dietary threonine has even been shown to recover the microbial diversity lost from experimentally induced stress, while also enhancing the abundance of beneficial bacteria (including populations of Enterobacteria, Lactobacillus, Bacteroides, and Enterococci). It’s possible that the mucin secretion threonine promotes along the GI tract serves as substrate for these beneficial microorganisms, in turn helping their populations grow. Of course, more research is needed in humans to understand the role of threonine in our own gut health!
Threonine and Bone Health
Although threonine would be expected to support bone health due to its role in forming collagen and elastin, very little research has examined this specifically. One study did show that threonine (along with the amino acids lysine, methionine, tryptophan, and isoleucine) is able to increase the activation, proliferation, and differentiation of osteoblasts (bone-building cells) while decreasing the activity of osteoclasts (bone-degrading cells). This suggests that threonine could be therapeutic for bone disorders like osteoporosis, but much more research is needed on the topic.
Threonine and Wound Healing
Some evidence also suggest that threonine could help support wound healing, especially for leg ulcerations. A handful of trials showed that threonine supplementation (sometimes in conjunction with other amino acids) improved the healing of hypostatic leg ulceration, although benefits were less clear for other injuries. Again, more research is needed!
Health Effects of Threonine Deficiency
Threonine deficiency is relatively rare, but can sometimes occur due to malnourishment, very low protein diets, or malabsorption disorders. When it’s been studied experimentally in animals, threonine deficiency has been shown to impair mucin production in the gut, alter lipid metabolism in the liver (leading to the buildup of liver fat), and increase the susceptibility to seizures.
How Much Threonine Do We Need?
The World Health Organization recommends that adults consume about 15 mg per kg (or 6.8 mg per lb) of body weight daily. In the context of certain health conditions (such as sepsis, inflammation, and inflammatory bowel diseases), this requirement may be higher in order to maintain adequate mucin production in the gut.
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