Children's HealthNutritionSoy Protein

Research Highlights Relevant to Soy Isoflavones, SIF, Ultra-processed Foods and Protein Quality

By September 30, 2021 No Comments
Research Highlights Relevant to Soy Isoflavones, SIF, Ultra-processed Foods and Protein Quality


Soy isoflavones and Alzheimer’s disease

Although isoflavones are routinely classified as endocrine disruptors (EDs) a recent comprehensive technical review that focused on the observational and clinical data concluded this designation is unwarranted.1 That is one reason a new narrative review by Polish researchers entitled, “The Beneficial Role of Natural Endocrine Disruptors: Phytoestrogens in Alzheimer’s Disease” is so germane to soy.2

As the title suggests, these researchers concluded that despite being classified by some as EDs, phytoestrogens can be beneficial in the prevention of Alzheimer’s disease. Although isoflavones were not the only phytoestrogens evaluated, much of the cited research involved these soybean constituents. The authors suggested that in the near future, phytoestrogens will become a promising treatment for Alzheimer’s disease. The point of highlighting this narrative review is not to argue that isoflavones prevent Alzheimer’s disease, although a recently published meta-analysis of the clinical data did find that isoflavones improved cognitive function.3 Rather, it is to point out that this team of researchers recognizes isoflavones are often classified as EDs, while also recognizing their potential benefits.

Soy infant formula

Soy infant formula (SIF) has been used for decades and in the not too distant past, it was estimated that 36% of Americans used SIF.4 Nevertheless, and despite the conclusion of the American Academy of Pediatrics that SIF promotes normal growth and development,5 SIF is controversial.6 This controversy exists primarily because SIF contains isoflavones. This is why the results of a new retrospective study from Korea make such an important contribution to the literature.7

This study — the largest observational study to examine the health impact of SIF —   investigated the effect of consuming SIF 9-12 months after birth on the subsequent development of epilepsy, neurodevelopmental disorders, and developmental status. A national database of children born in the Republic of Korea during 2008 and 2009 (n = 917,707) was used for recruitment. A total of 153,841 eligible participants were enrolled; 11,535 (7.5%) children received SIF, while 142,864 (92.5%) received cow’s milk formula. The median follow up duration was 8.9 years.  After matching for 92 baseline demographic and clinical variables, there were 10,951 infants fed SIF and 21,892 fed cow’s milk formula. The results showed that feeding with SIF rather than cow’s milk formula had no apparent association with epilepsy, attention-deficit hyperactivity disorder, autism spectrum disorder, and developmental status including puberty onset.

Plant-based meat alternatives and ultra-processed foods

According to the NOVA food classification system, plant-based meat alternatives (PBMA) are classified as ultra-processed foods (UPF, group 4) whereas hamburgers are classified as unprocessed or minimally processed foods (group 1).8,9 Many health experts are calling for limiting the intake of UPF10  because the intake of UPF is associated with an array of adverse health outcomes.11

However, in a recent paper, Russian investigators argued that  “… the mere industrial processing of ingredients of plant origin does not make a PBMA product ultra-processed by default.”12 They supported their argument by generating new clinical data from a study involving 40 participants that showed when PBMA replaced meat approximately 5 times per week, there was an improvement in the microbiome. This finding aligns with previously published research showing that when consuming about two servings daily of PBMA instead of meat, cholesterol and trimethylamine oxide (possible marker of heart disease risk) levels were decreased.13

Soy burger receives high protein quality score

The protein digestibility corrected amino acid score (PDCAAS) is the method accepted by many regulatory bodies around the world, including the USDA, for evaluating protein quality. However, the digestible indispensable amino acid score (DIAAS) has been proposed as one of the methods to potentially replace the PDCAAS.  University of Illinois researchers recently determined that when using the indispensable amino acid requirements for the older child, adolescent and adult, the Impossible Burger had a DIAAS of 107%, which as the authors note, allows it to be classified as an excellent protein source according to the FAO. The score for the Impossible Burger, for which soy is the primary protein source, was similar to 80% lean ground beef.  The Beyond Burger received a score of 83%, which as noted by  the authors, allows it to be classified as a good, but not excellent, source of protein. The primary protein source in the Beyond Burger is pea protein.1


  1. Messina M, Mejia SB, Cassidy A, et al. Neither soyfoods nor isoflavones warrant classification as endocrine disruptors: a technical review of the observational and clinical data. Crit Rev Food Sci Nutr. 2021:1-57.
  2. Domańska A, Orzechowski A, Litwiniuk A, et al. The beneficial role of natural endocrine disruptors: Phytoestrogens in Alzheimer’s disease. Oxidative Medicine and Cellular Longevity. 2021.
  3. Cui C, Birru RL, Snitz BE, et al. Effects of soy isoflavones on cognitive function: a systematic review and meta-analysis of randomized controlled trials. Nutr Rev. 2020;78:134-44.
  4. Merritt RJ, Jenks BH. Safety of soy-based infant formulas containing isoflavones: the clinical evidence. J Nutr. 2004;134:1220S-4S.
  5. Bhatia J, Greer F. Use of soy protein-based formulas in infant feeding. Pediatrics. 2008;121:1062-8.
  6. McCarver G, Bhatia J, Chambers C, et al. NTP-CERHR expert panel report on the developmental toxicity of soy infant formula. Birth Defects Res B Dev Reprod Toxicol. 2011;92:421-68.
  7. Ha EK, Lee SW, Kim JH, et al. Neurodevelopmental outcomes in infants fed with soy formula: A retrospective, national population-based observational cohort study. J Nutr. 2021.
  8. Monteiro CA, Cannon G, Levy R, et al. NOVA. The star shines bright. [Food classification. Public health]. World Nutrition. 2016;7:28-38.
  9. Monteiro CA, Moubarac JC, Cannon G, et al. Ultra-processed products are becoming dominant in the global food system. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2013;14 Suppl 2:21-8.
  10. Wickramasinghe K, Breda J, Berdzuli N, et al. The shift to plant-based diets: are we missing the point? Global Food Security. 2021;29:100530.
  11. Lane MM, Davis JA, Beattie S, et al. Ultraprocessed food and chronic noncommunicable diseases: A systematic review and meta-analysis of 43 observational studies. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2021;22:e13146.
  12. Toribio-Mateas MA, Bester A, Klimenko N. Impact of plant-based meat alternatives on the gut microbiota of consumers: A real-world study. Foods. 2021;10:2040.
  13. Crimarco A, Springfield S, Petlura C, et al. A randomized crossover trial on the effect of plant-based compared with animal-based meat on trimethylamine-N-oxide and cardiovascular disease risk factors in generally healthy adults: Study With Appetizing Plantfood-Meat Eating Alternative Trial (SWAP-MEAT). Am J Clin Nutr. 2020;112:1188-99.
  14. Fanelli NS, Bailey HM, Thompson TW, et al. Digestible indispensable amino acid score (DIAAS) is greater in animal-based burgers than in plant-based burgers if determined in pigs. Eur J Nutr. 2021.

 This blog sponsored by the Soy Nutrition Institute and the United Soybean Board.

Dr. Mark Messina

Author Dr. Mark Messina

PhD in Nutrition, Executive Director, Soy Nutrition Institute. Expert in soyfoods and isoflavones.

More posts by Dr. Mark Messina

Comments will be reviewed by the website moderator, but are not guaranteed to be posted.