Amino Acids and Fatty Acids: When the Diet Doesn't Cover the Needs

Calculating the right amount of protein in a diet does not mean the body will get enough essential amino acids. With fats, the situation is even more fundamental: omega-3 fatty acids can come as EPA and DHA — that is, in the form of long-chain polyunsaturated fatty acids available to the body without further conversion — or as ALA, a precursor that needs desaturase and elongase enzymes to be converted into EPA and DHA.

The nutritional value of a diet depends not only on the amount of nutrients in the foods that make it up. The decisive role is also played by how fully the body can absorb each of these nutrients. So judging how balanced a diet is by its composition alone would be a crude oversimplification.

Not all protein foods have the same amino acid composition

20 g of protein from fish and 20 g of protein from legumes mean different amino acid compositions. The amino acid profile depends on the source: plant proteins often contain less of certain essential amino acids than animal proteins. If a diet relies on a narrow range of protein sources, some essential amino acids may be supplied in insufficient amounts even when total protein intake looks adequate.

There is another level of variability. The requirement for protein and amino acids depends on age, physiological state, and physical activity. Studies using the indicator amino acid oxidation method show a wide range of protein requirement estimates depending on the group and conditions.

Protein requirement cannot be reduced to a single number. It involves at least a match between the amount of protein and the body's needs, a sufficient amino acid profile, and the bioavailability of amino acids.

For fatty acids, the form is key: ALA needs further conversion into long-chain omega-3s, whereas the body gets EPA and DHA in this long-chain form right away, with no such conversion required. So the same amount of omega-3 from food does not necessarily mean the same amount of a specific fatty acid available for further metabolism.

Essential amino acids come from food

The adult body can synthesize only 11 of the 20 proteinogenic amino acids. The other nine are essential, which means they must come from food.

The nutritional value of protein depends not only on its total amount but also on its amino acid composition — how well the quantity and proportions of essential amino acids can meet the body's needs. At the same time, even an optimal amino acid composition does not guarantee equal availability of amino acids for absorption: their digestibility depends on the protein source.

DIAAS is a measure of how well a protein supplies the body with essential amino acids. It takes into account both their amount and their absorption in the small intestine. The score is determined by the amino acid that is absorbed least relative to requirements: the higher the DIAAS, the better the protein covers those requirements. The resulting value is compared with the reference content of that amino acid. This approach makes it possible to assess protein quality while accounting for differences in the digestibility of individual amino acids, not just the overall digestibility of the protein (FAO, Dietary Protein Quality Evaluation in Human Nutrition, 2013).

In some plant sources, the content of certain essential amino acids is lower and their ileal digestibility is lower than in many animal sources. At the same time, these values vary considerably depending on the specific food, and combining different protein sources in the diet can make up for a low content of individual essential amino acids.

The requirement for essential amino acids also varies depending on physiological state and life stage. It is assessed using metabolic methods, in particular indicator amino acid oxidation (IAAO), which makes it possible to determine the requirement for a specific amino acid from the change in oxidation of an indicator amino acid at different intake levels of the amino acid being studied. The IAAO method has been used to estimate requirements in various age and physiological groups, although the available studies do not cover all life stages and populations (Matsumoto et al., J. Nutr., 2023).

From ALA to EPA and DHA: where individual variability arises

Among polyunsaturated fatty acids, omega-3s are one of the most studied groups. At the same time, omega-3s include several fatty acids that differ in their biological roles:

• DHA is an important structural component of cell membranes, especially in the brain and retina
• EPA takes part in the synthesis of signaling molecules that regulate inflammatory processes
• ALA is a precursor of EPA and DHA, but its conversion into these long-chain fatty acids is limited and varies between people (Calder, Proc. Nutr. Soc., 2020).

So, to assess omega-3 intake, it is important to consider its form: if omega-3s come mainly as ALA, the supply of EPA and DHA will depend, among other things, on the efficiency of endogenous conversion.

α-Linolenic acid (ALA) is an essential omega-3 fatty acid that humans get from plant foods. The main sources of ALA are flaxseed, walnuts, canola and soybean oils, chia seeds, and so on. The body can convert only part of the ALA consumed into the long-chain EPA and DHA: about 5–12% is converted into EPA and less than 1% into DHA, and conversion is more efficient in women than in men (Takić et al., Int. J. Mol. Sci., 2024). Therefore, flaxseed and other plant sources of ALA are not an equivalent substitute for fish and other sources that contain EPA and DHA.

Converting ALA requires the sequential work of desaturase and elongase enzymes. This pathway involves, in particular, enzymes encoded by the FADS1 (fatty acid desaturase 1) and FADS2 (fatty acid desaturase 2) genes, whose genetic variants are associated with differences in the concentrations of long-chain polyunsaturated fatty acids. A meta-analysis of eight studies showed that carriers of the A allele of FADS1 rs174556 have lower blood concentrations of EPA and DHA compared with other genotypes, although for DHA this association was sensitive to the analysis method (Wu et al., Adv. Nutr., 2023).

A broader scoping review of 40 studies confirms the link between common FADS and ELOVL variants and circulating EPA and DHA levels: the four FADS1 variants (rs174537, rs174547, rs174556, rs174561) turned out to be the most studied, and carriers of the minor allele had lower EPA and DHA levels (Loukil et al., Genes Nutr., 2024).

Thus, the efficiency of converting ALA into EPA and DHA differs between people. And genetic variants of FADS are among the factors behind this difference. At the same time, carrying a FADS genetic variant does not mean that a particular person has or will have an omega-3 deficiency at any given moment. A genetic association describes a predisposition, not current nutrient status.

The significance of FADS genetic variants depends on the omega-3 source in the diet

A genetic variant does not act outside its environment: the outcome is shaped at the same time by the dietary sources of fatty acids, their amount, physiological state, and other metabolic factors.

The role of endogenous ALA conversion grows when omega-3 fatty acids come mainly from plant-based food. If a person regularly eats fatty fish and so gets EPA and DHA directly, the efficiency of this conversion matters less.

Nutrient adequacy: from diet to metabolism

For a healthy person, a varied diet that provides the recommended intake of essential nutrients remains the foundation of nutrition. However, the same amount of a nutrient in the diet does not necessarily mean the same biological availability or the same metabolic outcome.

Thus, a carefully calculated protein norm does not guarantee getting all essential amino acids in the required amount. Likewise, the total amount of omega-3 in the diet does not guarantee a supply of EPA and DHA, nor does it show how efficiently ALA is converted into these forms.

Therefore, assessing nutrient status should rely on several levels of information:

• the composition and amount of nutrients in the diet
• the form in which they are supplied
• features of individual metabolism and nutrient conversion
• biomarkers that reflect actual nutrient status
• genetic variants associated with the relevant metabolic pathways.

In Apixmed Prism, the “Lipids, Cholesterol and Fatty Acids” DNA test analyzes markers and genetic variants associated with fatty acid metabolism, in particular with the conversion of ALA into the long-chain omega-3 fatty acids EPA and DHA. The “Amino Acids” DNA test analyzes variants associated with the metabolism of valine, leucine, isoleucine, methionine, threonine, tryptophan, phenylalanine, arginine, and other amino acids.

Such data show the genetic variability of metabolic pathways — one more layer of information alongside data on diet, biomarkers, and physiological state, which together allow a more accurate assessment of a particular person's nutrient status.

Explore the genetic features of amino acid and fatty acid metabolism with Apixmed Prism — look at your health through the lens of DNA.

Genetic test results are not a diagnosis and not a substitute for consulting a doctor. The Apixmed Prism report provides genetic context that complements the results of examinations and helps you make decisions together with your doctor.

Sources

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2. Loukil I, Mutch DM, Plourde M. (2024). Genetic association between FADS and ELOVL polymorphisms and the circulating levels of EPA/DHA in humans: a scoping review. Genes & Nutrition, 19(1), 11. https://doi.org/10.1186/s12263-024-00747-4

3. Matsumoto M, Narumi-Hyakutake A, Kakutani Y, Tsuji M, Hatamoto Y, Higaki Y, Sasaki S. (2023). Evaluation of protein requirements using the indicator amino acid oxidation method: a scoping review. Journal of Nutrition, 153(12), 3472–3489. https://doi.org/10.1016/j.tjnut.2023.07.015

4. Tome D, Xipsiti M, Shertukde SP, Calvez J, Vasilopoulou D, Wijesinha-Bettoni R, Owino VO. (2024). Context and Perspectives for Establishing a Novel Database for Protein Quality of Human Foods, as Proposed by a Joint FAO/IAEA Expert Technical Meeting in October 2022. Journal of Nutrition, 154(2), 294–299. https://doi.org/10.1016/j.tjnut.2023.12.050

5. Takić M, Ranković S, Girek Z, Pavlović S, Jovanović P, Jovanović V, Šarac I. (2024). Current Insights into the Effects of Dietary α-Linolenic Acid Focusing on Alterations of Polyunsaturated Fatty Acid Profiles in Metabolic Syndrome. International Journal of Molecular Sciences, 25(9), Article 4909. https://doi.org/10.3390/ijms25094909

6. FAO. (2013). Dietary Protein Quality Evaluation in Human Nutrition: Report of an FAO Expert Consultation. Food and Agriculture Organization of the United Nations. https://openknowledge.fao.org/handle/20.500.14283/i3124e

7. Calder PC. (2020). Omega-3 (n-3) polyunsaturated fatty acids and inflammation: From membrane to nucleus and from bench to bedside. Proceedings of the Nutrition Society. https://doi.org/10.1017/S0029665120007077