Skip to main content
    • Aa
    • Aa

Safety of soya-based infant formulas in children

  • Yvan Vandenplas (a1), Pedro Gutierrez Castrellon (a2), Rodolfo Rivas (a3), Carlos Jimenez Gutiérrez (a2), Luisa Diaz Garcia (a3), Juliana Estevez Jimenez (a2), Anahi Anzo (a3), Badriul Hegar (a4) and Pedro Alarcon (a5)...

Soya-based infant formulas (SIF) containing soya flour were introduced almost 100 years ago. Modern soya formulas are used in allergy/intolerance to cows' milk-based formulas (CMF), post-infectious diarrhoea, lactose intolerance and galactosaemia, as a vegan human milk (HM) substitute, etc. The safety of SIF is still debated. In the present study, we reviewed the safety of SIF in relation to anthropometric growth, bone health (bone mineral content), immunity, cognition, and reproductive and endocrine functions. The present review includes cross-sectional, case–control, cohort studies or clinical trials that were carried out in children fed SIF compared with those fed other types of infant formulas and that measured safety. The databases that were searched included PubMed (1909 to July 2013), Embase (1988 to May 2013), LILACS (1990 to May 2011), ARTEMISA (13th edition, December 2012), Cochrane controlled trials register, Bandolier and DARE using the Cochrane methodology. Wherever possible, a meta-analysis was carried out. We found that the anthropometric patterns of children fed SIF were similar to those of children fed CMF or HM. Despite the high levels of phytates and aluminium in SIF, Hb, serum protein, Zn and Ca concentrations and bone mineral content were found to be similar to those of children fed CMF or HM. We also found the levels of genistein and daidzein to be higher in children fed SIF; however, we did not find strong evidence of a negative effect on reproductive and endocrine functions. Immune measurements and neurocognitive parameters were similar in all the feeding groups. In conclusion, modern SIF are evidence-based safety options to feed children requiring them. The patterns of growth, bone health and metabolic, reproductive, endocrine, immune and neurological functions are similar to those observed in children fed CMF or HM.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Safety of soya-based infant formulas in children
      Available formats
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Safety of soya-based infant formulas in children
      Available formats
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Safety of soya-based infant formulas in children
      Available formats
Corresponding author
* Corresponding author: Y. Vandenplas, fax +32 24775783, email
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

4 American Academy of Pediatrics (1998) Soy-protein formulas: recommendations for use in infant feeding. Pediatrics 101, 148153.

9 A Chen & WJ Rogan (2004) Isoflavones in soy infant formula: a review of evidence for endocrine and other activity in infants. Ann Rev Nutr 24, 3354.

11 PG Tuohy (2003) Soy infant formula and phytoestrogens. J Paediatr Child Health 39, 401405.

12 C Essex (1996) Phytoestrogens and soy-based infant formula: risks remain theoretical. BMJ 313, 507508.

16 TH Shepard , GE Pyne , JF Kirschvink , et al. (1960) Soybean goiter. N Engl J Med 262, 10991103.

20 GK Powell (1978) Milk- and soy-induced enterocolitis of infancy: clinical features and standardization of challenge. J Pediatr 93, 553560.

22 G Zoppi , G Zamboni , N Bassani , et al. (1979) Gammaglobulin level and soy-protein intake in early infancy. Eur J Pediatr 131, 6169.

24 JC Callenbach , MB Sheehan , SJ Abramson , et al. (1981) Etiologic factors in rickets of very-low-birth-weight infants. J Pediatr 98, 800805.

26 JR Poley & AW Klein (1983) Scanning electron microscopy of soy protein-induced damage of small bowel mucosa in infants. J Pediatr Gastroenterol Nutr 2, 271287.

27 RT Hall , JC Callenbach , MB Sheehan , et al. (1984) Comparison of calcium- and phosphorus-supplemented soy isolate formula with whey-predominant premature formula in very-low-birth-weight infants. J Pediatr Gastroenterol Nutr 3, 571576.

28 R Dagan , R Gorodischer & SW Moses (1984) Dietary treatment of acute diarrhea: comparison between cow's milk and a soy formula without disaccharides. J Trop Pediatr 30, 221224.

33 N Iyngkaran , M Yadav , LM Looi , et al. (1988) Effect of soy protein on the small bowel mucosa of young infants recovering from acute gastroenteritis. J Pediatr Gastroenterol Nutr 7, 6875.

37 SA Bock & FM Atkins (1990) Patterns of food hypersensitivity during 16 years of double-blind, placebo-controlled food challenges. J Pediatr 117, 561567.

44 AW Burks , HB Castee , SC Fiedorek , et al. (1994) Prospective oral food challenge study of two soybean protein isolates in patients with possible milk or soy protein enterocolitis. Pediatr Allergy Immunol 5, 4045.

46 C Magnolfi , G Zani , L Lacava , et al. (1996) Soy allergy in atopic children. Ann Allergy Asthma Immunol 77, 197201.

48 MA Jabbar , J Larrea & RA Shaw (1997) Abnormal thyroid function tests in infants with congenital hypothyroidism: the influence of soy-based formula. J Am Coll Nutr 16, 280282.

49 A Cantani & P Lucenti (1997) Natural history of soy allergy and/or intolerance in children, and clinical use of soy protein formulas. Pediatr Allergy Immunol 8, 5974.

55 PLBJ Lucassen , WJJ Assendelft , JW Gubbels , et al. (1998) Effectiveness of treatments for infantile colic: systematic review. BMJ 316, 15631569.

56 WA Burks , JM James , A Hiegel , et al. (1998) Atopic dermatitis and food hypersensitivity reactions. J Pediatr 132, 132136.

62 G Zoppi & S Guandalini (1999) The story of soy formula feeding in infants: a road paved with good intentions. J Pediatr Gastroenterol Nutr 28, 541543.

64 LR Goldman , R Newbold & SH Swan (2001) Exposure to soy-based formula in infancy. JAMA 286, 24022403.

67 K Ostrom , MW Borschel , JE Westcott , et al. (2002) Lower calcium absorption in infants fed casein hydrolysate- and soy protein-based infant formulas containing palm olein versus formulas without palm olein. J Am Coll Nutr 21, 564569.

68 T Klemola , T Vanto , K Juntunen-Backman , et al. (2002) Allergy to soy formula and to extensively hydrolyzed whey formula in infants with cow's milk allergy: a prospective, randomized study with a follow-up to the age of 2 years. J Pediatr 140, 219224.

71 N Stettler , VA Stallings , AB Troxel , et al. (2005) Weight gain in the first week of life and overweight in adulthood: a cohort study of European American subjects fed infant formula. Circulation 111, 18971903.

75 T Hays & RA Wood (2005) A systematic review of the role of hydrolyzed infant formulas in allergy prevention. Arch Pediatr Adolesc Med 159, 810816.

76 S Berger-Achituv , T Shohat , O Romano-Zelekha , et al. (2005) Widespread use of soy-based formula without clinical indications. J Ped Gastroenterol Nutr 41, 660666.

77 T Klemola , K Kalimo , T Poussa , et al. (2005) Feeding a soy formula to children with cow's milk allergy: the development of immunoglobulin E-mediated allergy to soy and peanuts. J Pediatr Allergy Immunol 16, 641646.

78 C Agostoni , I Axelsson , O Goulet , et al. (2006) Soy protein infant formulae and follow-on formulae: a commentary by the ESPGHAN Committee on Nutrition. J Ped Gastroenterol Nutr 42, 352361.

80 E D'Auria (2006) Impact of soy formulas on growth. J Ped Gastroenterol Nutr 42, 594595.

82 K Ostrom , JR Jacobs , RJ Merritt , et al. (2006) Decreased regurgitation with a soy formula containing added soy fiber. Clin Pediatr (Phila) 45, 2936.

83 B Ballmer-Weber , T Holzhauser , J Scibilia , et al. (2007) Clinical characteristics of soybean allergy in Europe: a double-blind, placebo-controlled food challenge study. J Allergy Clin Immunol 119, 14891496.

84 E Fortes , M Malerba , P Luchini , et al. (2007) Ingestão excessiva de fitoestrógenos e telarca precoce: relato de caso compossível correlação (Excessive ingestion of phyto-oestrogens and precocious thelarche: case report with a possible correlation). Arq Bras Endocrinol Metab 51, 500503.

85 BM Halm , LA Ashburn & AA Franke (2007) Isoflavones from soya foods are more bioavailable in children than adults. Br J Nutr 98, 9981005.

86 D Turck (2007) Soy protein for infant feeding: what do we know? Curr Opin Clin Nutr Metab Care 10, 360365.

87 WO Song , OK Chun , I Hwang , et al. (2007) Soy isoflavones as safe functional ingredients. J Med Food 10, 571580.

89 MS Wolff , JA Britton , L Boguski , et al. (2008) Environmental exposures and puberty in inner-city girls. Environ Res 107, 393400.

90 L Zuidmeer , K Goldhahn , R Rona , et al. (2008) The prevalence of plant food allergies: a systematic review. J All Clin Immunol 121, 12101218.

96 J Bernbaum , D Umbach , NB Ragan , et al. (2008) Pilot studies of estrogen-related physical findings in infants. Environ Health Perspect 116, 416420.

98 L Caminiti , LG Passalacqua , S Barberi , et al. (2009) A new protocol for specific oral tolerance induction in children with IgE-mediated cow's milk allergy. Asthma Allergy Proc 30, 443448.

101 SA Lee , XO Shu , H Li , et al. (2009) Adolescent and adult soy food intake and breast cancer risk: results from the Shanghai Women's Health Study. Am J Clin Nutr 89, 19201926.

102 L Korde , AH Wu & T Fears (2009) Childhood soy intake and breast cancer risk in Asian American women. Cancer Epidemiol Biomarkers Prev 18, 10501059.

103 JF Guest & E Nagy (2009) Modelling the resource implications and budget impact of managing cow milk allergy in Australia. Curr Med Res Opin 25, 339349.

104 J Palmer , A Herbst , K Noller , et al. (2009) Urogenital abnormalities in men exposed to diethylstilbestrol in utero: a cohort study. Environ Health 8, 37.

105 CH Cederroth , A Zimmermann , F Eustache , et al. (2010) Soy, phyto-oestrogens and male reproductive function: a review. Int J Andrology 33, 304316.

106 Y Vandenplas , E De Greef , T Devreker , et al. (2011) Soy infant formula: is it that bad? Acta Pædiatr 100, 162166.

107 A Dias , A Santos & JA Pinheiro (2010) Persistence of cow's milk allergy beyond two years of age. Allergol Immunopathol (Madr) 38, 812.

108 S Bolca , M Urpi-Sarda , P Blondeel , et al. (2010) Disposition of soy isoflavones in normal human breast tissue. Am J Clin Nutr 91, 976984.

109 G Cheng , T Remer , R Prinz-Langenohl , et al. (2010) Relation of isoflavones and fiber intake in childhood to the timing of puberty. Am J Clin Nutr 92, 556564.

111 T Tillet (2010) Soy formula of “minimal concern”. Environ Health Perspect 118, A335A336.

113 E Sladkevicius , E Nagy , G Lack , et al. (2010) Resource implications and budget impact of managing cow milk allergy in the UK. J Med Econ 13, 119128.

114 Y Katz , N Rajuan , M Goldberg , et al. (2010) Early exposure to cow's milk protein is protective against IgE-mediated cow's milk protein allergy. J Allergy Clin Immunol 126, 7782.

115 H Patisaul & W Jefferson (2010) The pros and cons of phytoestrogens. Front Neuroendocrinol 31, 400419.

117 E Dinsdale & W Ward (2010) Early exposure to soy isoflavones and effects on reproductive health: a review of human and animal studies. Nutrients 2, 11561187.

120 J Kim , S Kim , K Huh , et al. (2011) High serum isoflavone concentrations are associated with the risk of precocious puberty in Korean girls. Clin Endocr (Oxf) 75, 831835.

121 JD Kattan , RR Cocco & KM Järvinen (2011) Milk and soy allergy. Pediatr Clin N Am 58, 407426.

122 R Dabeka , A Fouquet , S Belisle , et al. (2011) Lead, cadmium and aluminum in Canadian infant formulae, oral electrolytes and glucose solutions. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 28, 744753.

124 R Nguyen , D Umbach , R Parad , et al. (2011) US assessment of estrogen-responsive organ growth among healthy term infants: piloting methods for assessing estrogenic activity. Pediatr Radiol 41, 633642.

125 W Jefferson & C Williams (2011) Circulating levels of genistein in the neonate, apart from dose and route, predict future adverse female reproductive outcomes. Reprod Toxicol 31, 272279.

127 SA Levy , SD Dortas Junior , AH Pires , et al. (2012) Atopy patch test (APT) in the diagnosis of food allergy in children with atopic dermatitis. An Bras Dermatol 87, 724728.

130 F Crinella (2012) Does soy-based infant formula cause ADHD? Update and public policy considerations. Expert Rev Neurother 12, 395407.

131 JL Kay , CW Daeschner Jr & MM Desmond (1960) Evaluation of infants fed soybean and evaporated milk formulae from birth to three months. A comparison of weight, length, hemoglobin, hematocrit, plasma biochemical values. Am J Dis Child 100, 264276.

132 FF Cherry , MD Cooper , RA Stewart , et al. (1968) Cow versus soy formulas. Comparative evaluation in normal infants. Am J Dis Child 115, 677692.

135 AL Jung & SL Carr (1977) A soy protein formula and a milk-based formula. A comparative evaluation in milk-tolerant infants showed no significant nutritional differences. Clin Pediatr (Phila) 16, 982985.

136 G Zoppi , F Gerosa , A Pezzini , et al. (1982) Immunocompetence and dietary protein intake in early infancy. J Pediatr Gastroenterol Nutr 1, 175182.

140 LS Hillman , W Chow , SS Salmons , et al. (1988) Vitamin D metabolism, mineral homeostasis and bone mineralization in term infants fed human milk, cow milk-based formula or soy-based formula. J Pediatr 112, 864874.

142 F Mimouni , B Campaigne , M Neylan , et al. (1993) Bone mineralization in the first year of life in infants fed human milk, cow-milk formula or soy-based formula. J Pediatr 122, 348354.

143 M Giovannini , C Agostoni , A Fiocchi , et al. (1994) Antigen-reduced infant formulas versus human milk: growth and metabolic parameters in the first six months of life. J Am Coll Nutr 13, 357363.

144 JB Lasekan , KM Ostrom , JR Jacobs , et al. (1999) Growth of newborn, term infants fed soy formulas for one year. Clin Pediatr 38, 563571.

148 MH Malloy & H Berendes (1998) Does breastfeeding influence intelligence quotients at 9 and 10 years of age? Early Hum Dev 50, 209217.

149 BL Strom , R Shinnar , EE Ziegler , et al. (2001) Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA 286, 807814.

152 L Businco , G Bruno , ME Grandolfo , et al. (1990) Response to poliovirus immunization and type of feeding in babies of atopic families. Pediatr Allergy Immunol 1, 6063.

155 J Bhatia & F Greer (2008) Use of soy protein-based formulas in infant feeding. Pediatrics 121, 10621068.

156 KD Setchell , L Zimmer-Nechemias , J Cai , et al. (1997) Exposure of infants to phyto-oestrogens from soy-based infant formula. Lancet 350, 2327.

157 Y Cao , AM Calafat , DR Doerge , et al. (2009) Isoflavones in urine, saliva and blood of infants: data from a pilot study on the estrogenic activity of soy formula. J Expo Sci Environ Epidemiol 19, 223234.

159 MA Adgent , JL Daniels , WJ Rogan , et al. (2012) Early-life soy exposure and age at menarche. Paediatr Perinat Epidemiol 26, 163175.

160 A Zung , T Glaser , Z Kerem , et al. (2008) Breast development in the first two years of life: an association with soy-based infant formulas. J Pediatr Gastroenterol Nutr 46, 191195.

163 SC Conrad , H Chiu & BL Silverman (2004) Soy formula complicates management of congenital hypothyroidism. Arch Dis Child 89, 3740.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 79
Total number of PDF views: 654 *
Loading metrics...

Abstract views

Total abstract views: 1936 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 23rd August 2017. This data will be updated every 24 hours.