History of Soy Nutritional Research (1990-2021)

William Shurtleff, Akiko AoyagiISBN: 978-1-948436-33-5

Publication Date: 2021 Feb. 20

Number of References in Bibliography: 4547

Earliest Reference: 1990

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Brief Chronology/Timeline of the History of Soy Nutrition (1990-2021)

For this book, we give our deepest thanks to the U.S. National Library of Medicine for PubMed, its free search engine accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics.

Human nutritional studies are the hallmark of this time period – for two main reasons.

Mark Messina, PhD, who worked for the National Cancer Institute, was deeply interested in understanding whether consuming soyfoods could reduce one’s risk of getting cancer or dying from it. He soon became especially interested in the potential health benefits of isoflavones.

By 1990 soyfoods (such as tofu, soymilk, tempeh, soynuts, and miso) were widely available in the USA and Europe because of the soyfoods movement and the arrival of immigrants from Asia based on the Immigration Act of 1965, which went into effect in 1968.

During the period 1990 to 2020 the number of publications on health and of soyfoods increased dramatically – from 500 papers in 1990 to 1560 papers in 2000, to 2707 in 2010, to a peak of 3443 papers in 2019. These numbers resulted from a search on PubMed for the words isoflavones, genistein, daidzein, equol, soy, soya or plant estrogen.

During the period from 1990 to 2000, when soy was really “hot,” the number of papers on isoflavones (isoflavones, genistein, daidzein, or equol) also increased dramatically - from 96 papers in 1990 to 840 papers in 2000, rising more slowly to a near-peak of 1059 in 2007 and a peak of 1089 papers in 2014.

This research was mainly in the following health-related areas: Heart disease. Bone health. Menopausal symptoms. Breast cancer. Prostate cancer. Cognitive function. Thyroid health. Reproductive health. And Skin health.

Are soyfoods healthful and good for you?

My life’s work has been to study soybeans, and especially soyfoods. They form a regular part of my diet and I have written numerous books about them. I have read thousands of articles about soy nutritional research and written summaries of each – many of which appear in this 3-volume book on the history of soy nutritional research. I believe soyfoods are one of the best sources of protein in the world as part of a healthy diet. I also believe that soy is not a “magic bullet” that provides significant health benefits as part of an unhealthy diet. As with all things, there are pros and cons.


Soybeans contain the highest quantity of protein (about 40%) and that protein is of very high quality. By all modern measures of protein quality, soyfoods are the highest of all plant proteins and equal to eggs, milk and meat. Moreover soy protein is very inexpensive when purchased as widely used soyfoods such as tofu, soymilk, edamame, tempeh and miso.

Soy, as a plant protein, has relatively low carbon footprint – for those of us concerned about global warming and living lightly on planet Earth.

Soyfoods make it possible to enjoy a delicious, healthy vegan diet, which is kind to animals in factory farms.

Soybeans are a good source of vitamins A, C, thiamine and riboflavin, and a fair source of other B vitamins.

Soyfoods, especially typical tofu and soymilk, are very good sources of calcium, and that calcium is well absorbed. Look for tofu curded with calcium and soymilk fortified with calcium.

Soybeans, like all plant-based foods, contain no cholesterol, and they are rich in polyunsaturated fat and a source of both essential amino acids (linolenic acid and alpha-linolenic acid).

Soyfoods contain lecithin, which has a host of health benefits; it may even reduce wrinkles.

If you start consuming soyfoods at an early age, it may reduce your risk of breast cancer and prostate cancer.

Soyfoods may alleviate menopausal hot flashes. This is especially true among women who are high producers of the metabolite equol. But only about 25% of Westerners have equol-producing bacteria in their intestines, compared to roughly 50% of East Asians.

While much of the fat is of the polyunsaturated omega-6 type, soyfoods are one of the few good plant sources of the essential omega-3 fatty acid ALA.

Soyfoods probably place less stress on kidney function than do animal products.

Soyfoods contain isoflavones, a type of phytoestrogens (plant estrogens), which are vastly less potent than female estrogens - typically 1/100 to 1/10,000. They bind to the same receptors in cells – a necessary step for biological action – that the female hormone estrogen binds. When they bind to (dock at) an estrogen receptor, that prevents a female estrogen from docking there – thereby reducing the body’s exposure to estrogen. The less exposure to female estrogen, the lower the risk (in general) of breast cancer.


Soy is one of the top 8 allergens. Yet it is by far the least problematic of the eight. Those allergic to soy are mostly infants and children, but that allergy largely disappears after they become teenagers.

Soybeans are high in anti-nutrients such as phytate (which can bind minerals), oxalate (which can lead to kidney stones), and lectins.

Soy is being grown on land in Brazil that was formerly rain forest. Now, however, expanding onto new rain-forest land in Brazil is illegal.

Most of the soybeans grown in the USA are genetically engineered (often incorrectly called “genetically modified”), however most of those used for soyfoods are organically grown and certified to be not genetically engineered by the Non-GMO Project.

Soy protein is relatively low in the sulfur-containing amino acids methionine and cystine – Nevertheless it is the highest quality plant protein. Moreover it is high in lysine, which is the limiting amino acid in cereal grains.


1990 June 27 – A workshop on “The role of soy products in cancer prevention” is organized by Mark Messina, PhD, of the Diet and Cancer Branch, National Cancer Institute. It is held at the NIH main campus in Bethesda, Maryland. A summary of each of the 20-minute papers and a commentary (“The role of soy products in reducing risk of cancer”) by Messina and S. Barnes is published on 17 April 1991 in the Journal of the National Cancer Institute (v.83, p. 541-46).

Note: As of Feb. 2021 - according to Google Scholar - this is Mark Messina's 2nd most widely cited paper, cited in 898 publications.

1990 Sept. – Dr. Dean Ornish's Program for Reversing Heart Disease: The Only System Scientifically Proven to Reverse Heart Disease Without Drugs or Surgery is published by Random House. This pioneering, bestselling book by a physician and head of the Preventive Medicine Research Inst. in California, featured soyfoods.

The results of Ornish's study, recently published in the British medical journal Lancet are dramatic. 82% of the patients who followed Ornish's program showed a decrease in arterial blockage and reported less pain. Dr. Ornish was the first to prove that lifestyle changes alone – without drugs – could reverse arterial heart disease.

1991 – In response to recommendations of the 5th session of the Codex Committee on Vegetable Proteins (CCVP) held in Ottawa, Canada, a joint FAO/WHO Expert Consultation on Protein Quality Evaluation was held in Bethesda, Maryland, USA from December 4-8 1989... This publication is a report of that meeting's findings.

The Consultation concluded that the protein

digestibility-corrected amino acid score (PDCAAS) method was the most suitable approach for routine evaluation of protein quality for humans and recommended the adoption of this method as an official method at the international level” (FAO Food and Nutrition Paper No. 51).

1991 April 17 – “The role of soy products in reducing risk of cancer: Commentary,” by Mark Messina and Stephen Barnes is published in the J. of the National Cancer Institute (p. 541-46). This paper and the symposium on which it is based have far-reaching consequences.

The symposium was held on 27 June 1990 at the National Cancer Institute (NCI), Bethesda, Maryland. The symposium was organized by Mark Messina, PhD, Program Director, Diet and Cancer Branch, Div. of Cancer Prevention and Control, NCI.

This is also the earliest document seen containing the word “nutraceutical” in connection with soy.

1992 May 8 – Mark Messina decides to leave his position as a Program Director, Diet and Cancer Branch at the National Cancer Institute to devote more of his time to research on and promotion of soyfoods. He would also like to speak, write, do consulting, and organize a conference now and then on soybeans and/or soyfoods.

1992 early summer – Richard and Valerie James, a retired American couple living in New Zealand, notice that their beautiful exotic and native birds are starting to die mysteriously and become very sick. Richard is a lawyer by training; he uses his legal skills to try to track down the cause of this disaster. He finally decides that the cause is toxins in the soybean meal, which is an ingredient in his parrot feed. After hiring Mike Fitzpatrick, and contacting many others who feed soybean meal in New Zealand and Australia, he finds many others who are having similar problems. So he and Fitzpatrick begin a campaign to warn others of the dangers of soy. He is quickly attacked by those selling soyfoods and feeds, soy ingredients and soy-based infant formula in New Zealand, yet he also receives widespread, sympathetic media coverage. The anti-soy campaign has begun.

1992 Dec. – Writing in the Yearbook of Agriculture (USDA), James A. Duke, PhD, first uses the word “nutriceuticals” (spelled that way) in connection with soy.

1992 – Menopausal symptoms. Adlercreutz et al. suggested that the low prevalence of hot flashes reported by Japanese menopausal women might be at least partially due to their high consumption of soyfoods. Speculation was that the estrogen-like effects of isoflavones might mitigate the drop in estrogen levels, one trigger for hot flashes that occurs when women enter menopause. More than 50 hot flash trials evaluating the efficacy of isoflavone-containing products have been conducted. Most analyses have found suggestive evidence supporting the efficacy of isoflavones but did not reach definitive conclusions because of the conflicting data.

1993 April – “Genistein, a dietary-derived inhibitor of in vitro angiogenesis,” by Fotsis, Pepper, Adlercreutz, et al. is published in the Proceedings of the American Academy of Sciences (p. 2690-94). This extremely important article describes angiogenesis, the mechanism by which the isoflavones (especially genistein) in soybeans inhibit the growth of some tiny cancerous tumors by blocking the growth of new capillaries that supply blood to those tumors.

For tumors to grow beyond 1-2 mm in size, it is thought they need to foster development of new blood vessels (neovascularization) in order to receive the nutrients and oxygen required for growth.

People consuming a traditional Japanese diet were found to have 30 times as much genistein in their urine as typical Westerners.

1993 JuneThe Soy Connection, a newsletter sent mainly to registered dietitians, begins publication. It is funded by the United Soybean Board in Chesterfield, Missouri. Mark Messina PhD has a major article in most issues. By July 1993 it is mailed to about 70,000 people free of charge.

1993 – Protein digestibility-corrected amino acid score (PDCAAS) is a method of evaluating the quality of a protein based on both the amino acid requirements of humans and their ability to digest it. The PDCAAS rating was adopted by the US Food and Drug Administration (FDA) and the Food and Agricultural Organization of the United Nations/World Health Organization (FAO/WHO) in 1993 as "the preferred 'best'" method to determine protein quality.

1994 Feb. 20-23 – First International Symposium on the Role of Soy in Preventing and Treating Chronic Disease is held in Mesa, Arizona. Organized by Mark Messina and sponsored by Protein Technologies International, the United Soybean Board as well as soybean growers from Nebraska and Indiana, it focuses on heart disease and cancer. The proceedings are published in the Journal of Nutrition (March 1995). The word “Soy” starts to be used in a new way (see title); it used to refer to soy sauce.

Subsequent symposia, all (except the last) with the same title and organized by Messina were held: (2) 1996 Sept. 15-16, Brussels, Belgium; (3) 1999 Oct. 31-Nov. 3, Washington, DC; (4) 2001 Nov. 4-7, San Diego, California; (5) 2003 Sept. 21-24, Orlando, Florida; (6) 2005 Oct. 30-Nov. 2, Chicago, Illinois; (7) 2007 March 7-9, Bangkok, Thailand; (8) 2008 Nov. 9-12, Tokyo, Japan.

1994 April – “Soy intake and cancer risk: A review of the in vitro and in vivo data,” by Mark Messina et al. is published in Nutrition and Cancer (p. 113-31).

Note: As of Feb. 2021 – according to Google Scholar - this is Mark Messina's most widely cited paper, cited in 1,858 publications.

1994 AprilThe Simple Soybean and Your Health, a book by Mark Messina, PhD, Virginia Messina, RD, and Kenneth D.R. Setchell is published. It shows (among other things) how soyfoods can lower your cholesterol and reduce your risk of heart disease and cancer. The authors are outstanding educators and writers who present complex ideas in an accurate yet easy to understand manner. Mark Messina received his master’s degree from the University of Michigan, and his doctorate from Michigan State Univ., both in nutrition science.

1994 May – The term “Functional Foods” is first used in connection with soy (Rutgers University). It has arrived to replace words like “nutraceutical” and “nutriceutical.”

1995 Jan. – “Neonatal genistein chemoprevents mammary cancer,” by Coral A. Lamartiniere et al. is published in Proceedings of the Society for Experimental Biology. It shows that early intake of genistein, an estrogenic component of soy, reduces later risk of breast cancer in rats. The importance of “early intake” of soy by humans eventually becomes one of the most important soy-related discoveries of the next 25 years.

1995 March – “Modern applications for an ancient bean: soybeans and the prevention and treatment of chronic disease,” by Mark Messina is published in a special issue of the Journal of Nutrition, which publishes many papers and some abstracts from the First International Symposium.

1995 June 15 – The use of estrogens and progestins can increase the risk of breast cancer, reports the New England Journal of Medicine. The analysis is based on the Nurses' Health Study, which has followed 121,700 women nurses since 1972.

On the other hand, estrogen has been found to cut in half a woman's risk of heart disease, which is the leading cause of death for woman as well as men. It has a similar impact on fractures, a major cause of disability. For a women 50 or 60 years of age, her risk of dying from heart disease is six times greater than dying from breast cancer.

1995 Aug. 3 – “Meta-analysis of the effects of soy protein intake on serum lipids,” by James W. Anderson et al. is published in the New England J. of Medicine (p. 276-82). Note: This statistical analysis of 38 scientific studies is probably the most significant and influential article on the health / medical benefits of soyfoods to be published to date. It received widespread media coverage and led to a large jump in soyfoods consumption in the USA. The article begins: “Ingestion of vegetable protein in place of animal protein appears to be associated with a lower risk of coronary heart disease.”

1997 July 5 – Infants consuming soy formula have extremely high plasma isoflavone is shown by Kenneth D. Setchell et al. in “Exposure of infants to phyto-estrogens from soy-based infant formula” (Lancet 350, p. 23-27). Is this early exposure good news or bad?

1997 Nov. 15 – New research suggesting that genistein and daidzein in soybeans are goitrogenic in vitro is published by R.L. Divi et al. in “Anti-thyroid isoflavones from soybean: isolation, characterization, and mechanisms of action,” in Biochemical Pharmacology (54, p. 1087-96). Subsequent research shows this not to be a problem for humans.

1997 Nov. – Phytoestrogens extracted from soybeans, made by ADM and sold in pill/supplement form under the brand name Novosoy, are launched in the USA. These soy capsules are sold in two sizes: 135 mg and 700 mg.

1998 Jan. – The American Academy of Pediatrics, Committee on Nutrition, recommends soy protein-based infant formulas under certain conditions: Above all, the academy “is committed to the use of maternal breast milk as the ideal source of nutrition for infant feeding. Even so, by 2 months of age, most infants in North America are formula-fed. Despite limited indications, the use of soy protein-based formula has nearly doubled during the past decade to achieve 25% of the market in the United States.”

“Conclusions and recommendations: 1. In term infants whose nutritional needs are not being met from maternal breast milk or cow milk-based formulas, isolated soy protein-based formulas are safe and effective alternatives to provide appropriate nutrition for normal growth and development.

"2. Because soy protein-based formulas are lactose-free, they are appropriate for use in infants with galactosemia and hereditary lactase deficiency.

"3. Parents seeking a vegetarian-based diet for a term infant can be advised to use isolated soy protein-based formula." There are 6 other conclusions (Pediatrics, p. 148-53).

1998 Sept. 1 – Genistein stimulates the growth of existing mammary tumors in rats is shown by C.Y. Hsieh et al. in “Estrogenic effects of genistein on the growth of estrogen receptor-positive human breast cancer (MCF-7) cells in vitro and in vivo.” (Cancer Research. 58, p. 3833-3838). This is potentially bad news for soy. Yet subsequent research shows that because laboratory animals metabolize phytochemicals differently, it is not. Likewise, other studies on lab animals turn out to be of limited value in understanding how soy affects humans.

1999 Oct. 26 – U.S. Food and Drug Administration (FDA) authorizes the use of a qualified health claim about the role of soy protein in reducing the risk of coronary heart disease (CHD) on labeling of foods containing soy protein. In order to qualify for this health claim, a food must contain at least 6.25 grams of soy protein per serving. This announcement starts a stampede among food manufacturers. Those which already have such foods on the market, rush to put the FDA claim and logo on their label. Many companies which previously had little or no interest in soy, rush to launch new soy protein products which would qualify for the FDA heart-health claim. This heart health claim can be seen as a high point for the soyfoods movement – and the start of its decline.

2000 April/Sept. – Sally Fallon and the anti-soy faction begin to gain momentum. “Tragedy and hype: The Third International Soy Symposium,” by Sally Fallon and Mary Enig (Nexus magazine {New Zealand} (April/May, 2000. p. 15-20, 69; July p. 66-71; Aug/Sept, p. 56-58). This article, in an obscure, popular magazine, contains 72 references.

2000 April – Tofu intake is linked with brain atrophy. Lon R. White et al write “Brain aging and midlife tofu consumption” (J. of the American College of Nutrition. 19, 242-255). This association was later shown to be untrue. For more balance and perspective, see the editorial by Grodstein et al. published in this same issue.

2002 Dec. – Individuals who host certain gut bacteria that are able to convert daidzein to equol may benefit more from consuming soyfoods. K.D. Setchell et al. write “The clinical importance of the metabolite equol – a clue to the effectiveness of soy and its isoflavones.” (J. of Nutrition. 132, p. 3577-3584).

2005 March 9 - A 440-page French-language report concludes that soy and its isoflavones have few if any definitive health benefits. Author: Agence française de sécurité sanitaire des aliments (AFSSA; [French Food Safety Agency]). Title: Sécurité et bénéfices des phyto-estrogènes apportés par l'alimentation – Recommandations AFSSA [Safety and benefits of phytoestrogens found in food –AFSSA recommendations - French Food Safety Agency]. Nancy, France, 440 p., 171 references.

2005 July – Agency for Health Research and Quality (AHRQ) concludes in a long and detailed report that soy has few if any definitive health benefits. E. Balk et al. “Effects of soy on health outcomes. Evidence report/technology assessment No. 126 (prepared by Tufts-New England Medical Center Evidence-based Practice Center under Contract No. 290-02-0022.) AHRQ Publication No. 05-E024-2.” Rockville, MD: Agency for Healthcare Research and Quality.

2005 Feb. – The Whole Soy Story: The Dark Side of America’s Favorite Health Food, by Kaayla T. Daniel is published in Washington, DC, by New Trends Publishing, Inc. (xviii + 457 p.; 1,797 references); It is the first completely anti-soy book yet published.

2006 March – Clinical studies show no effects of soy on thyroid function; it is not a goitrogen in humans. Mark Messina & G. Redmond write “Effects of soy protein and soybean isoflavones on thyroid function in healthy adults and hypothyroid patients: a review of the relevant literature” (Thyroid 16, p. 249-258).

2006 Feb. 21 – The American Heart Association (AHA) concludes soy has few if any benefits beyond nutrient content. F.M. Sacks et al. write “Soy protein, isoflavones, and cardiovascular health: an American Heart Association Science Advisory for professionals from the Nutrition Committee.” (Circulation 113, p. 1034-1044).

2008 June – Case report of soy consumption feminizing an older man who was drinking 3 quarts of soymilk each day. Martinez & Lewi write “An unusual case of gynecomastia associated with soy product consumption” Endocrine Practice (14, p. 415-418).

2008 Nov. – Soy intake associated with lower sperm count. J.E. Chavarro et al. write “Soy food and isoflavone intake in relation to semen quality parameters among men from an infertility clinic.” Human Reproduction (23, p. 2584-2590).

2009 June – Article claiming soy feminizes men. “Is This the Most Dangerous Food for Men?,” by Jim Thorton. (Men's Health, June 4).

2009 Dec. 9 – Post-diagnosis soy intake improves the prognosis of breast cancer survivors. X.O. Shu et al. write “Soy food intake and breast cancer survival” (JAMA 302, p. 2437-2443).

2010 Jan. – Three-year intervention study showing isoflavone supplements don't reduce bone loss in postmenopausal women. D.L. Alekel DL et al. write “The soy isoflavones for reducing bone loss (SIRBL) study: a 3-y randomized controlled trial in postmenopausal women” (American J. of Clinical Nutrition 91, 218-230).

2010 Aug. – Neither soy nor isoflavones lower testosterone levels: Meta-analysis results. J.M. Hamilton-Reeves et al. write “Clinical studies show no effects of soy protein or isoflavones on reproductive hormones in men: results of a meta-analysis” (Fertility and Sterility 94, p. 997-1007).

2011 Oct. – The National Toxicology Program evaluates safety of soy infant formula in 2009-2010. They have minimal concern. G. McCarver et al. write “NTP-CERHR expert panel report on the developmental toxicity of soy infant formula.” (Birth Defects Research Part B: Developmental and Reproductive Toxicology 92, p. 421-468).

2012 Feb. – High-dose soy isoflavones may protect against breast cancer development; they don't increase in vivo breast cell proliferation. S.A. Khan et al. write “Soy isoflavone supplementation for breast cancer risk reduction: A randomized phase II trial” (Cancer Prevention Research {Philadelphia} 5, p. 309-319).

2013 March – Digestible Indispensable Amino Acid Score (DIASS) is a protein quality method, proposed in March 2013 by the Food and Agriculture Organization to replace the existing protein ranking standard, the Protein Digestibility Corrected Amino Acid Score (PDCAAS).

2014 Feb. – Isoflavones may reduce wrinkles. G. Jenkins et al. write “Wrinkle reduction in post-menopausal women consuming a novel oral supplement: a double-blind placebo-controlled randomized study” (International J. of Cosmetic Science 36, p. 22-31).

2017 Oct. 31 – FDA announces intention to revoke soy protein health claim. https://www.federalregister.gov/documents/2017/10/31/2017-23629/food-labeling-health-claims-soy-protein-and-coronary-heart-disease.

As of Feb. 2021 no action has been taken by FDA on this soy health claim.

2018 May – Soy infant formula exerts estrogenic effects on tissues of female infants. M.A. Adgent et al. write “A longitudinal study of estrogen-responsive tissues and hormone concentrations in infants fed soy formula (J. of Clinical Endocrinology & Metabolism 103, p. 1899-1909).

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