Based on an analysis of NHANES III (Third National Examination and Nutritional Health Survey Study (1988-1994) data, Pennsylvania State University researchers recently found that diets lower in sulfur amino acids (SAAs), that is, diets closest to the estimated average requirement (EAR), are associated with reduced risk for cardiometabolic diseases.1 This is not the first time that the two SAAs, methionine and cysteine, have been implicated in disease etiology.2 And the research may have implications for soyfoods, suggesting benefits to including them in the diet.
The Penn State researchers found that after multivariable adjustment, higher intake of SAAs was associated with significant increases in composite cardiometabolic disease risk score. Factors comprising the risk score included blood cholesterol, triglycerides, HDL, C-reactive protein, uric acid, glucose, blood urea nitrogen, glycated hemoglobin, insulin, and estimated glomerular filtration rate. The association between SAA intake and risk was independent of traditional cardiovascular disease risk factors, including body mass index, diabetes, and hypertension.
Among the 11,576 participants, average intake of SAA (39.2 ± 18.1 mg/kg/day) was more than 2.5-fold higher than the EAR for adults (15 mg/kg/day). Among participants in the highest SAA quintile, intake was more than 4-times the EAR.
Could the association between cardiometabolic disease risk and SAA intake simply be the result of an overall higher protein intake? Not according to the results of a secondary analyses of the data. When SAA intake was expressed as a percentage of total protein intake, referred to as protein density, the findings were relatively unchanged. In addition, animal studies have shown mechanistic support for a relationship between SAA intake and cardiometabolic risk factors.3
The authors of this study suggest moderating the intake of legume products and diluting total protein intake by ingestion of ample amounts of fruits and other foods. They also suggested that “… reduced SAA intake may be in part, responsible for beneficial health effects attributed to plant-based diets.”1
But not everyone agrees with recommendations to reduce protein intake. The Acceptable Macronutrient Distribution Range (AMDR) for protein established by the Institute of Medicine (now National Academy of Medicine) is 10 to 35% of calories.4 U.S. protein intake falls close to the lower end of the range, at about 16%.5 Also, there is considerable suggestive evidence that the Recommended Dietary Allowance (RDA) for protein is too low for most population groups.6-13 Higher protein intake may be particularly beneficial for maintaining muscle mass in older people14 and could be useful for protecting against muscle loss in weight reduction and maintenance.15
One theory proposed by the Penn State researchers is that the beneficial health effects associated with plant-based diets could be due in part to their lower SAA content. Schmidt et al.16 found that among participants in the Oxford arm of the European Prospective Investigation into Cancer and Nutrition (EPIC-Oxford), vegan (n=98) methionine intake was about 50% lower (0.88 vs 1.67 g/d) than omnivore (n=98) intake; however, when expressed as a percentage of total protein intake, the difference between vegans and omnivores was only about 25% (1.53 vs 2.04 g/d), since the vegans consumed less protein overall. The difference between lacto-ovo vegetarians and omnivores was only about 15% (1.73 vs 2.04 g/d) on a per gram protein basis.1 (In the Adventist Health Study 2, total protein intake was similar between omnivores and vegetarians/vegans).17 However, SAA intake is just one difference between vegetarian and non-vegetarian diets as vegetarian diets are much higher in fiber and lower in saturated fat. 17
The recommendation made by the Penn State researchers to moderate legume intake is questionable given the important contribution that these foods make to lysine intake on plant- based diets.18 Furthermore, legumes currently make a negligible contribution to the protein intake of Americans and therefore have little impact on SAA intake.5 Given the nutrient content and health benefits of these foods19 and their potential as a sustainable protein source, it makes sense for Americans to increase their intake of legumes.20 Current dietary guidelines from many countries, including the US, encourage bean consumption. 21
Finally, as a percentage of total protein content, legumes are relatively low in SAA (see table below) which is not surprising since SAAs are the limiting amino acids in these foods.
Amino acid score for the sulfur amino acids for selected proteins (excludes digestibility)
|Food (100 g edible portion)||Nutrient|
|Amino acid score*|
|0-3 years||>3 years|
The SAA content of a protein on a mg/g protein basis versus the SAA requirement established by the Food and Agriculture Organization of the United Nations for two age groups, 6 months to 3 years (27 mg/g protein) and >3 years (23 mg/g protein)
Soyfoods may have a particular benefit among legumes since the amount of soy needed to meet the protein RDA also meets (or comes close to meeting) requirements for all essential amino acids but without exceeding the requirements for the SAAs.22,23 In contrast, consuming the RDA for total protein in the form of grains would not only exceed the SAA requirement but would provide insufficient amounts of the essential amino acid lysine.22,23 Meat and dairy protein meet the requirements for all the essential amino acids; they exceed the SAA requirement (see table).22,23 In addition, soy protein modestly lowers blood cholesterol levels.24
In the past, SAAs were implicated as a risk factor for osteoporosis due to their proposed effects on endogenous acid production. 2,25 As a result, soy protein was singled out for possible skeletal benefits due to its high-quality but lower amounts of the SAAs.26 However, subsequent clinical27,28 and epidemiologic29 research has failed to support this theory. Whether a similar fate awaits the hypothesis proposed by Dong et al.1 is unknown. In the meantime, the totality of the evidence indicates soy protein and soyfoods are healthful choices.
- Dong Z, Gaob X, Chinchillia VM, et al. Association of sulfur amino acid consumption with cardiometabolic risk factors: Cross-sectional findings from NHANES III. EClinicalMedicine. 2019.
- Trilok G, Draper HH. Sources of protein-induced endogenous acid production and excretion by human adults. Calcif Tissue Int. 1989;44(5):335-8.
- Dong Z, Sinha R, Richie JP, Jr. Disease prevention and delayed aging by dietary sulfur amino acid restriction: translational implications. Ann N Y Acad Sci. 2018;1418(1):44-55.
- Institute of Medicine of the National Academies. 2005. P. 686 Dietary reference intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids. National Academy Press, Washington, DC.
- Shan Z, Rehm CD, Rogers G, et al. Trends in dietary carbohydrate, protein, and fat intake and diet quality among US adults, 1999-2016. JAMA. 2019;322(12):1178-87.
- Bandegan A, Courtney-Martin G, Rafii M, et al. Indicator amino acid-derived estimate of dietary protein requirement for male bodybuilders on a nontraining day is several-fold greater than the current recommended dietary allowance. J Nutr. 2017;147(5):850-7.
- Bandegan A, Courtney-Martin G, Rafii M, et al. Indicator amino acid oxidation protein requirement estimate in endurance-trained men 24 h postexercise exceeds both the EAR and current athlete guidelines. American journal of physiology Endocrinology and metabolism. 2019;316(5):E741-E8.
- Rafii M, Chapman K, Elango R, et al. Dietary protein requirement of men >65 years old determined by the indicator amino acid oxidation technique is higher than the current estimated average requirement. J Nutr. 2016;146681-7.
- Rafii M, Chapman K, Owens J, et al. Dietary protein requirement of female adults >65 years determined by the indicator amino acid oxidation technique is higher than current recommendations. J Nutr. 2015;145(1):18-24.
- Elango R, Humayun MA, Ball RO, et al. Protein requirement of healthy school-age children determined by the indicator amino acid oxidation method. Am J Clin Nutr. 2011;94(6):1545-52.
- Humayun MA, Elango R, Ball RO, et al. Reevaluation of the protein requirement in young men with the indicator amino acid oxidation technique. Am J Clin Nutr. 2007;86(4):995-1002.
- Stephens TV, Payne M, Ball RO, et al. Protein requirements of healthy pregnant women during early and late gestation are higher than current recommendations. J Nutr. 2015;145(1):73-8.
- Tang M, McCabe GP, Elango R, et al. Assessment of protein requirement in octogenarian women with use of the indicator amino acid oxidation technique. Am J Clin Nutr. 2014;99(4):891-8.
- Traylor DA, Gorissen SHM, Phillips SM. Perspective: Protein requirements and optimal intakes in aging: Are we ready to recommend more than the recommended daily allowance? Adv Nutr. 2018;9(3):171-82.
- Longland TM, Oikawa SY, Mitchell CJ, et al. Higher compared with lower dietary protein during an energy deficit combined with intense exercise promotes greater lean mass gain and fat mass loss: a randomized trial. Am J Clin Nutr. 2016;103(3):738-46.
- Schmidt JA, Rinaldi S, Scalbert A, et al. Plasma concentrations and intakes of amino acids in male meat-eaters, fish-eaters, vegetarians and vegans: a cross-sectional analysis in the EPIC-Oxford cohort. Eur J Clin Nutr. 2015.
- Rizzo NS, Jaceldo-Siegl K, Sabate J, et al. Nutrient profiles of vegetarian and nonvegetarian dietary patterns. Journal of the Academy of Nutrition and Dietetics. 2013;113(12):1610-9.
- Mariotti F, Gardner CD. Dietary protein and amino acids in vegetarian diets-A review. Nutrients. 2019;11(11).
- Hall C, Hillen C, Robinson JG. Composition, nutritional value, and health benefits of pulses. Cereal Chem. 2017;94(1):11-31.
- Clark MA, Springmann M, Hill J, et al. Multiple health and environmental impacts of foods. Proc Natl Acad Sci U S A. 2019;116(46):23357-62.
- Marinangeli CPF, Curran J, Barr SI, et al. Enhancing nutrition with pulses: defining a recommended serving size for adults. Nutr Rev. 2017;75(12):990-1006.
- Hughes GJ, Ryan DJ, Mukherjea R, et al. Protein digestibility-corrected amino acid scores (PDCAAS) for soy protein isolates and concentrate: Criteria for evaluation. J Agric Food Chemistry. 2011;59(23):12707-12.
- Mathai JK, Liu Y, Stein HH. Values for digestible indispensable amino acid scores (DIAAS) for some dairy and plant proteins may better describe protein quality than values calculated using the concept for protein digestibility-corrected amino acid scores (PDCAAS). Br J Nutr. 2017;117(4):490-9.
- Blanco Mejia S, Messina M, Li SS, et al. A meta-analysis of 46 studies identified by the FDA demonstrates that soy protein decreases circulating LDL and total cholesterol concentrations in adults. J Nutr. 2019;149(6):968-81.
- Barzel US. The skeleton as an ion exchange system: implications for the role of acid-base imbalance in the genesis of osteoporosis. J Bone Miner Res. 1995;10(10):1431-6.
- Kaneko K, Masaki U, Aikyo M, et al. Urinary calcium and calcium balance in young women affected by high protein diet of soy protein isolate and adding sulfur-containing amino acids and/or potassium. J Nutr Sci Vitaminol (Tokyo). 1990;36(2):105-16.
- Roughead ZK, Hunt JR, Johnson LK, et al. Controlled substitution of soy protein for meat protein: effects on calcium retention, bone, and cardiovascular health indices in postmenopausal women. J Clin Endocrinol Metab. 2005;90(1):181-9.
- Roughead ZK, Johnson LK, Lykken GI, et al. Controlled high meat diets do not affect calcium retention or indices of bone status in healthy postmenopausal women. J Nutr. 2003;133(4):1020-6.
- Shams-White MM, Chung M, Du M, et al. Dietary protein and bone health: a systematic review and meta-analysis from the National Osteoporosis Foundation. Am J Clin Nutr. 2017;105(6):1528-43.