New research suggests increasing IAA intake by 1.6x

Tony Clark, CSO and Steve Fratini, PhD:  March 19, 2024
Updated: May 7, 2024

Intro

In the “Proteins and Amino Acids: The Charm Bracelets of Health” article, we discuss the relationship between protein and amino acids and remind readers of the wide range of critical biological processes that depend on the adequate daily consumption of indispensable amino acids (IAA).  In “What happens if you don’t eat enough protein?,” we address why it is important to consume an adequate amount of protein as part of a balanced diet.  And, in this article, we tackle the question of just how much protein is enough?

The current United States Department of Agriculture (USDA) and World Health Organization (WHO) recommendations, which address the amount of protein that we should consume, are 20 years old and much has happened since their initial publication.  The world in the mid-2020s is vastly different than it was at the turn of the century.  Adults are living longer, and are doing so with one or more chronic health conditions [1], which are correlated with diet. 

Given the prominent role of IAA in our daily diets, this ORIGINAL-RESEARCH article proposes Adjusted Dietary Reference Intakes* (ADRI) for IAA.  The IAA ADRI incorporate more recent evidence-based research and data, which suggest a higher baseline consumption of IAAs may be warranted to help offset the widespread prevalence of chronic health conditions. 

The IAA ADRI presented hereafter are for adults (> 18 years old) and explicitly consider the widespread prevalence of chronic physical disease and chronic mental illness in the adult population.  Readers should consider the IAA ADRI, presented hereafter, within the context of their specific health goals.

Protein and IAA DRI History

Recommended Dietary Allowance (RDA) is a subcategory of the USDA’s Dietary Reference Intakes (DRI).  The current RDA for protein is primarily based on the minimum amount of dietary protein that needs to be consumed to ensure that daily protein intake (absorption and synthesis) supplies an amount that is equal to the amount of protein that is lost each day [2].   In other words, protein consumption recommendations are generally specified to meet the requirements of protein turnover—the continuous process of breaking down and re-synthesizing body proteins for almost all healthy subjects. 

Readers may recall that the 37 trillion cells in our bodies, comprising our blood, muscle, skin, bone, enzymes, immune system cells and other tissues, are all made from protein; and as we are living beings, the timely replacement of our expired cells is critical to our continued well-being.  The thought underlying the protein RDA is that if one consumes protein at the DRI’s RDA level then theoretically one should be able to maintain their body’s total protein mass over time.  Thus, the consumption of protein at the RDA level is intended to ensure that individuals consume just enough protein to avoid a variety of resultant health consequences, inclusive of premature aging, hair loss, and unwanted weight gain.  That said, the RDA minimums for protein should not be confused with the amount of protein one should consume for optimal health**.

The respective government agencies that have assumed responsibility for defining the RDA for protein are the USDA [4] and the WHO [3].  The respective daily Protein RDA from the USDA and WHO are within 2% of each other.  The daily RDA of protein per the USDA for healthy adults (> 18 years of age) is 0.80 grams of protein per kilogram of body weight [2].  The RDA for protein per the WHO for healthy adults (> 18 years of age) is 0.83 grams of protein per kilogram of body weight [5] [38].

The current daily RDA for IAA, respectively from the USDA and WHO, are given in Table 1.  The respective USDA [2] and WHO [38] recommendations are for healthy, non-pregnant, non-lactating adults (> 18 years of age).  Generally, the WHO recommends slightly lower levels of each IAA compared to the USDA, except for Isoleucine and Valine.

Reasons to Consume More IAA Than the DRI/RDA Amount*

Originally published in 2005, by the Institute of Medicine [2], and based on nitrogen balance and other relevant studies reported in 2003 [6], the USDA DRI have long been criticized because the DRI fail to adequately account for protein digestibility challenges, the suitability of using nitrogen balance to estimate protein absorption and bioavailability, activity levels [37], and other limitations.  The same criticisms also apply to the WHO’s Protein DRI [5], which were reaffirmed in the same time frame. 

Moreover, much has happened in the subsequent 20 years, since the protein DRI were published.  We have suffered through and are still enduring a world-wide pandemic which has left numerous mental health and physical health challenges in its wake, including elevated levels of chronic stress and an amplified opioid overdose epidemic [7].  The world in the 2020s is vastly different than it was at the turn of the century.  A healthy adult today lives longer and has one or more chronic health conditions [1].  The current reexamination of the USDA and WHO Protein/IAA DRI, in light of these changes, is warranted.

More recent evidence-based, scientific research on wide-spread chronic health conditions and amino acids consumption reveals that the consumption of a higher baseline level of IAA, relative to what the USDA and WHO DRI prescribe, is desirable.   Chronic health conditions include (or are influenced by) mood disorders, stress, physical illness, pain, sleep dysfunction, smoking, drug use, and allergies: 

• Stress:  Stress affects us all [8].  Additionally, chronic stress is an under-reported epidemic, which can induce physical symptoms such as chest pain, headaches, anxiety, upset stomach, high blood pressure, depression, sexual dysfunction, and sleeplessness.  Nearly eight in ten Americans say they frequently or sometimes encounter stress in their daily lives, with the two most common contributors to stress being children and work [9] [10].  Stress interrupts normal sympathetic and para-sympathetic balance [8] [11]; resulting in longer stays in fight-or-flight mode.  More frequent fight-or-flight episodes negatively impact digestion by inducing diarrhea or constipation and / or reducing the activity of digestive enzymes, which independently and together can impair the digestibility of protein [8] [12] [13] [14].   Moreover, chronic stress may reduce the preference for high protein foods and may trigger cravings for high fat and high carbohydrate foods, resulting in less protein consumption [15].  Ironically, increased protein consumption reduces inflammatory immune system responses and improves gut barrier function [16].  A 2008 Australian diet and exercise clinical study, examining stress, exercise, and nutrition, found that general practitioner supplied counseling led to an 18% improvement in stress levels and was accompanied by a minimum average increase in protein consumption of 12.5% [17].

• Age:  We are living longer.  The percentage of people 65 and older in the North America and Europe has more than doubled since the 1970s and current projections suggest that 25% of the U.S. population will be aged 65 or older by 2050 [18].  In 2021, 48% of the U.S. population was 40 years old or older [19].  Moreover, studies have revealed a rapid decline (a 30% to 50% decrease) in muscle mass between the ages of 40 years and 80 years [20].  Meanwhile, new research affirms that older adults need more protein than is currently recommended for optimal health [21].  The increased need is in part due to a decreased ability to digest protein and in part due to an increase in the protein turnover rate for certain tissues [21], both of which accompany ageing.  The benefits of consuming more protein include the slower loss of bone density, muscle mass, and strength [22] [23] [24] [25] [26] [27].  Research recommends that older adults should consume at least 1.2 grams of protein [22], and up to 1.5 grams of protein [21], per kilogram of body weight.

• Chronic Illness and Pain:  A significant majority of American adults, 6 in 10, have at least one chronic disease and 4 in 10 have two or more chronic diseases [1].  Chronic diseases include systemic inflammation, heart disease, cancer, diabetes, asthma, chronic obstructive pulmonary disease (COPD), digestive diseases, Alzheimer’s, kidney disease and depression.   Chronic disease negatively alters protein synthesis, causing the loss of body protein and resulting in skeletal muscle wasting [8] [14] [21].   Increased protein consumption has been clinically found to help treat chronic digestive disease, primarily by improving the gut barrier [16][28].  Also, certain IAAs, inclusive of Tryptophan, play a support role in pain relief.  Moreover, clinical subjects who were given a supplement of 0.75 grams of protein per kilogram of body weight experienced lower esophageal sphincter pressure during acid reflux [29].  And, in a separate Crohn’s Disease study, patients who consumed an average diet consisting of a total of 1.8 grams of protein per kilogram of body weight**, instead of taking corticosteroids, experienced significantly improved disease symptoms and inflammatory markers [39].  Ironically, medications (e.g., antibiotics, non-steroidal anti-inflammatory drugs, etc.) taken to combat a chronic condition (e.g., recurrent urinary tract infection, headache, etc.) may disturb digestion, and consequently can reduce the normal uptake of dietary nutrients inclusive of IAAs [40].

Adjusted Dietary Reference Intakes for IAA*

The following adjusted IAA dietary reference intake levels have not been evaluated by the FDA and are not intended to diagnose or treat any disease.  That said, there is precedent for increasing the IAA DRI.  Note that the current WHO Protein DRI are about 10% higher than the values proposed by WHO in 1985 [5] and a separate meta-analysis found that protein requirements for adults are 10% higher than the WHO stated requirements [30]. 

Considering the above clinical study findings and the resultant increased metabolic requirements therein, the USDA and WHO IAA DRI appear to be inadequate to maintain a body’s total protein mass over time.  As such, we propose the following adjustments to the DRI (i.e., IAA ADRI).  And, for ease-of-compliance, we utilize a single, higher baseline for healthy adults (> 18 years old), which factors in rapidly changing demographics, the widespread effect of stress, epidemic levels of chronic diseases (e.g., Type 2 Diabetes), and pervasive chronic pain.

Our IAA Adjusted DRI (ADRI) assume a daily consumption of 1.35 grams of protein per kilogram of body weight and is informed by the clinical studies summarized earlier in this article.  Regarding the profile of the IAA ADRI, recall that in our 2-part article discussing the importance of protein quality,  we introduce and motivate why human milk is the ideal “gold-standard” for IAA composition.  Accordingly, our IAA ARDI calculations assume the IAA composition of human milk and are consistent with clinical research which has examined the role that the limiting IAA plays in overall protein synthesis [21].  Given these considerations we arrive at the Adjusted Dietary Reference Intakes for Indispensable Amino Acids in Table 2.  The ARDI’s 300 milligrams of total IAA are 22% of the total protein reference of 1.35 grams of protein per kilogram of body weight. These numbers include protein consumption from all sources (food and supplements). 

Protein and IAA Consumption Upper Limits

We now consider the IAA ARDI in the context of research-supported safe upper limits for protein and IAA consumption.   Generally, the USDA notes that the risk of adverse effects from excess protein intake from foods appears to be very low [2].  Consumption of protein at 2 grams per kilogram of body weight*** is considered safe for healthy adults, and the tolerable upper limit for protein consumption is 3.5 grams per kilogram of body weight for well adapted subjects [9].  Thus, the tolerable upper limit for protein is more than 2.5 times the ADRI amount for protein per this article.

Table 3 provides upper limits for the supplementation of IAAs beyond what an individual gets from their food consumption.  Further, the various studies on upper limits from IAA supplementation typically consider only one or a few of the IAAs at a time (potentially resulting in an unbalanced IAA distribution) and the doses are often not distributed throughout the day.  Numbers from the various papers are in bold, converted numbers are not in bold.

Summary

The IAA ADRI for adults (> 18 years old) presented in this article consider the growing prevalence of chronic illness and dramatic demographic shifts to arrive at a new set of reference intakes for indispensable amino acids, which are higher than those recommended by the USDA and WHO.  Readers should consider our research-supported IAA ADRI within the context of their specific goals for more optimal health.  We encourage you to discuss your particular needs with your doctor and / or nutritionist.

Footnotes

* ARDI are presented for educational purposes only, for the consideration by healthy adults (> 18 years old and older) who are not experiencing metabolic disorders involving impaired nitrogen utilization, kidney issues or other issues which may be exacerbated by the increased consumption of protein.  Please consult your doctor or nutritionist to discuss your specific situation.

** The daily average amount of protein consumed per exclusive enteral nutrition was 131.25 grams and the average weight of patients was 74.6 kilograms.

*** For the past 5 years, as part of an ongoing longitudinal case study exploring how much protein should be and can be safely consumed for more optimal health, co-author Tony Clark has consumed on average 2.1 grams of protein per kilogram of body weight per day.  He has experienced no negative side-affects from the consumption of protein at this level, which is nearly 3x the amount recommended by the USDA.  Although his results are positive, they are not sufficient and are not intended to make a recommendation to any member of the public.

Definitions for Upper Limits on IAAs

The following definitions are from the National Academy of Medicine (formerly Institute of Medicine) (2005). [6]

Estimated average requirement (EAR): the average daily nutrient intake level estimated to meet the requirement of half the healthy individuals in a particular life stage and gender group.

Recommended dietary allowance (RDA): the average daily dietary nutrient intake level sufficient to meet the nutrient requirement of nearly all (97% to 98%) healthy individuals in a particular life stage and gender group.

Adequate Intake (AI): the recommended average daily intake level based on observed or experimentally determined approximations or estimates of nutrient intake by a group (or groups) of apparently healthy people that are assumed to be adequate – used when an RDA cannot be determined.

Tolerable upper intake level (UL): the highest average daily nutrient intake level that is likely to pose no risk of adverse health effects to almost all individuals in the general population. As intake increases above the UL, the potential risk of adverse effects may increase.

No observed adverse effect level (NOAEL): highest intake (or experimental oral dose) of a nutrient at which no adverse effects have been observed.

Lowest observed adverse effect level (LOAEL): the lowest intake (or experimental oral dose) at which an adverse effect has been identified.

References

[1] CDC, Chronic Diseases in America.  Accessed Jan. 2024.  Chronic Diseases in America | CDC .

[2] Institute of Medicine, Dietary Reference Intakes: The Essential Guide to Nutrient Requirements. Washington, DC: The National Academies Press. 2006; Pages 144-155, 464 and 530. https://nap.nationalacademies.org/download/11537.

[3] World Health Organization (WHO), accessed Feb. 2024,  World Health Organization (WHO).

[4] U.S. Department of Agriculture, accessed Feb. 2024, USDA.

[5] World Health Organization, Protein and Amino Acid Requirements in Human Nutrition: Report of a Joint FAO/WHO/UNU Expert Consultation. ISSN 0512-3054; 2002; Pages 125-126. WHO Online text.

[6] Institute of Medicine, Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. 2005; Chapter 10.  https://doi.org/10.17226/10490.

[7] CDC, Understanding the Opioid Overdose Epidemic | Opioids.  Accessed January 26, 2024.  CDC Online text. 

[8] Konturek, P.C., et al., Stress And The Gut: Pathophysiology, Clinical Consequences, Diagnostic Approach and Treatment Options.  Journal of Physiology And Pharmacology; 2011; Vol. 62, No. 6; Pages 591-599.  https://www.jpp.krakow.pl/journal/archive/12_11/pdf/591_12_11_article.pdf .

[9] Saad, L. (2017, December 20). eight-americans-afflicted-stress.aspx. Retrieved August 11, 2020, from news.gallup.com: https://news.gallup.com/poll/224336/eight-americans-afflicted-stress.aspx.

[10] The United Nations, The Pandemic Accelerant: How COVID-19 Advanced Our Mental Health Priorities. Accessed Jan. 2024.  UN Online text. 

[11] Noushad, S., et al., Physiological biomarkers of chronic stress:  A systematic review.  International Journal of Health Science (Qassim). 2021; v.15(5); Pages 46-59. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8434839/.

[12] Leigh, S.J., et al., The impact of acute and chronic stress on gastrointestinal physiology and function: a microbiota-gut-brain axis perspective.  ISSN 0022-3751; 2023; The Journal of Physiology; Vol. 601; Issue 20; Pages 4469-4462.

[13] Cherpak, C.E., Mindful Eating: A Review of How The Stress-Digestion-Mindfulness Triad May Modulate And Improve Gastrointestinal And Digestive Function.  Integrative Medicine; 2019; Vol. 18, No. 4; Pages 48-53.

[14] Lee, S.P., et al., The Effect of Emotional Stress and Depression on the Prevalence of Digestive Diseases.  Journal of Neurogastroenterology and Motility; 2015; Vol. 21, No. 2; Pages 273-282.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4398234/pdf/jnm-21-273.pdf.

[15] Teegarden, S.L., et al., Effects of stress on dietary preference and intake are dependent on access and stress sensitivity.  Physiology & Behavior; 2008; Vol. 93, Issues 4-5; Pages 713-723.

[16] Ma, S., et al., Protein diets with the role of immune and gut microbial regulation alleviate DSS-induced chronic ulcerative colitis.  Food Science & Nutrition; 2020; Vol. 9; Pages 1259-1270.

[17] Forsyth, AK., A randomized controlled trial of nutrition and physical activity intervention for patients with depression and/or anxiety in primary care.  Doctor of Philosophy thesis; School of Health Sciences, University of Wollongong.  2013; Pages 136-143.

[18] United Nations Department of Economic and Social Affairs, Population Division (2022). World Population Prospects 2022: Summary of Results. UN DESA/POP/2022/TR/NO. 3.  www.unpopulation.org.

[19] United States Census Bureau, Age and Sex Composition in the United States: 2021.  Accessed February 2024.  Age and Sex Composition in the United States: 2021 (census.gov).

[20] Faulkner, J.A., et al., Age-related changes in the structure and function of skeletal muscles. Clin. Exp. Pharmacol. Physiol. 2007, 34, 1091–1096.  https://pubmed.ncbi.nlm.nih.gov/17880359/.

[21] Jonker, R., et al., Role of specific dietary amino acids in clinical conditions.  Br Journal of Nutrition; 2012; Vol. 108, Issue (0 2); Pages 139-148.

[22] Bauer J., et al., Evidence-Based Recommendations for Optimal Dietary Protein Intake in Older People: A Position Paper From the PROT-AGE Study Group. JAMDA Volume 14 Issue 8 (2013) 542-559.  https://www.jamda.com/article/S1525-8610(13)00326-5/fulltext .

[23] Promislow J.H., et al., Protein consumption and bone mineral density in the elderly: The Rancho Bernardo Study.  American Journal of Epidemiology, 2002; 155:636-644. https://academic.oup.com/aje/article/155/7/636/60202.

[24] Kerstetter J.E., et al., Low dietary protein and low bone density.  Calcified Tissue International, 2000; 66:313. Online text.

[25] Rapuri P.B., et. al., Protein intake: Effects on bone mineral density and the rate of bone loss in elderly women. American Journal of Clinical Nutrition, 2003; 77: 1517-1525. https://pubmed.ncbi.nlm.nih.gov/12791633/.

[26] Hannan M.T., et al., Effect of dietary protein on bone loss in elderly men and women: The Framingham Osteoporosis Study.  Journal of Bone and Mineral Research, 2000; Volume 15; Issue 12; Pages 2504-2512. https://asbmr.onlinelibrary.wiley.com/doi/full/10.1359/jbmr.2000.15.12.2504.

[27] Scott D., et al., Associations between dietary nutrient intake and muscle mass and strength in community-dwelling older adults: The Tasmanian Older Adult Cohort Study. Journal of American Geriatric Society, 2010; 58: 2129-2134.  https://pubmed.ncbi.nlm.nih.gov/21054294/.

[28] Liu, Y., et. al., Therapeutic Potential of Amino Acids in Inflammatory Bowel Disease.  Nutrients; 2017; Vol. 9, Issue 920.

[29] Gielkens HA., et al., Effect of amino acids on lower esophageal sphincter characteristics and gastroesophageal reflux in humans. Dig Dis Sci. 1998 Apr;43(4):840-6. doi: 10.1023/a:1018834618682. PMID: 9558042.

[30] Millward DJ., Identifying recommended dietary allowances for protein and amino acids: a critique of the 2007 WHO/FAO/UNU report. Br J Nutr. 2012 Aug;108 Suppl 2:S3-21. doi: 10.1017/S0007114512002450. PMID: 23107542.

[31] Luc Cynober, Dennis M Bier, Patrick Stover, Motoni Kadowaki, Sidney M Morris, Rajavel Elango, Miro Smriga, Proposals for Upper Limits of Safe Intake for Methionine, Histidine, and Lysine in Healthy Humans, The Journal of Nutrition, Volume 150, Supplement 1, 2020, Pages 2606S-2608S, ISSN 0022-3166, https://doi.org/10.1093/jn/nxaa231.

[32] Rajavel Elango, Tolerable Upper Intake Level for Individual Amino Acids in Humans: A Narrative Review of Recent Clinical Studies. Advances in Nutrition, Volume 14, Issue 4, 2023, Pages 885-894, ISSN 2161-8313, https://doi.org/10.1016/j.advnut.2023.04.004. (https://www.sciencedirect.com/science/article/pii/S2161831323002892)

[33] Blachier F, Blais A, Elango R, Saito K, Shimomura Y, Kadowaki M, Matsumoto H. Tolerable amounts of amino acids for human supplementation: summary and lessons from published peer-reviewed studies. Amino Acids. 2021 Sep;53(9):1313-1328. doi: 10.1007/s00726-021-03054-z. Epub 2021 Aug 2. PMID: 34338884; PMCID: PMC8416832.

[34] Cynober L, Bier DM, Kadowaki M, Morris SM Jr, Renwick AG. A proposal for an upper limit of leucine safe intake in healthy adults. J Nutr. 2012 Dec;142(12):2249S-2250S. doi: 10.3945/jn.112.160853. Epub 2012 Oct 24. PMID: 23096009.

[35] Hayamizu K, Oshima I, Nakano M., Comprehensive Safety Assessment of l-Lysine Supplementation from Clinical Studies: A Systematic Review. J Nutr. 2020 Oct 1;150(Suppl 1):2561S-2569S. doi: 10.1093/jn/nxaa218. PMID: 33000161.

[36] Cynober L, Bier DM, Kadowaki M, Morris SM Jr, Elango R, Smriga M., Proposals for Upper Limits of Safe Intake for Arginine and Tryptophan in Young Adults and an Upper Limit of Safe Intake for Leucine in the Elderly. J Nutr. 2016 Dec;146(12):2652S-2654S. doi: 10.3945/jn.115.228478. Epub 2016 Nov 9. PMID: 27934658.

[37] Wu G., Dietary protein intake and human health. Food Funct. 2016 Mar;7(3):1251-65. doi: 10.1039/c5fo01530h. PMID: 26797090. https://pubmed.ncbi.nlm.nih.gov/26797090/.

[38] Report of a Food and Agriculture Organization (FAO) of the United Nations Rome Expert Consultation, Dietary protein quality evaluation in human nutrition.  ISSN 0254-4725; 2013; Page 27.

[39] Wall, CL., et al., Treatment of Active Crohn’s Disease with Exclusive and Partial Enteral Nutrition:  A Pilot Study in Adults.  Inflammatory Intestinal Diseases. 2018; 2 (4): 219-227.

[40] Philpott HL, et al., Drug-induced gastrointestinal disorders. Frontline Gastroenterol. 2014 Jan;5(1):49-57. doi: 10.1136/flgastro-2013-100316. Epub 2013 Jun 19. PMID: 28839751; PMCID: PMC5369702.