Soy Protein Safety Concerns Lack Human Adverse Effect Data - FDA

Challenges to the safety of soy protein-containing foods failed to provide documented evidence of adverse effects in humans or any information "about actual levels of potentially harmful components or about threshold levels for adverse effects in humans," FDA says in its approved soy protein health claim.

In a final rule expected to be published in the Oct. 26 Federal Register, the agency says it has no reason to conclude soy protein is not safe and lawful. The rule authorizes a health claim for soy protein and the reduced risk of coronary heart disease on labeling for eligible foods (¹ (Also see "Soy Protein Health Claim For Reduced Heart Disease Clears FDA" - Pink Sheet, 25 Oct, 1999.)).

The agency reviewed numerous comments addressing concerns about estrogenic effects of soy isoflavones, including proliferative and potentially carcinogenic impacts on estrogen-sensitive tissues, effects on circulating hormone levels and potentially adverse consequences on fertility and sexual development.

Among the respondents on the issue were researchers from the HHS National Center for Toxicological Research, who cited animal studies suggesting the potential for estrogenic toxicity in humans (² (Also see "Soy Protein Toxicity Data Needed To Support Health Claim - Researchers" - Pink Sheet, 22 Mar, 1999.)).

"Soy isoflavones and other dietary phytoestrogens are known to exert hormonal effects - both estrogenic and antiestrogenic - depending on the amount and type consumed and endogenous hormonal status of the organism studied," FDA says, citing considerable individual variability in the absorption, metabolism and disposition of soy isoflavones.

"Overall, the evidence for proliferative effects, effects on fertility and hormone levels, and developmental and other effects in humans due to the estrogenic effects of soy isoflavones is very limited," FDA says. "Both possible beneficial effects and possible detrimental effects are still hypothetical. FDA finds that the information presented in the comments has not adequately documented deleterious effects of dietary intake of soy isoflavones in humans."

Some comments questioned the safety of soy protein-based infant formulas and cited observed or hypothesized detrimental effects such as hormonal disturbances, thyroid abnormalities, altered mineral balance and diabetogenic effects in infants.

"FDA is aware of concerns raised about the safety of soy infant formulas, but notes that these are speculative at this time, pending the results of definitive research," the final rule states.

"In any case, concerns about the effects of soy protein specific to infant formulas are beyond the scope of the current rule," which "contains no provisions for use of the health claim about the relationship between soy protein and CHD on foods for infants and toddlers."

Regarding potential allerginicity of soy protein, FDA agrees with one of the comments "that authorization of a health claim for soy protein and CHD will highlight the presence of soy protein in those food products that bear the claim. The agency, therefore, anticipates that persons with known soy allergies will be able more easily to avoid soy protein based products."

Some comments took issue with FDA's failure to conclude the isoflavone component is a relevant factor to the diet-disease relationship.

"The additional evidence about the role of isoflavones is contradictory and inconclusive and has not persuaded FDA to alter its original conclusion about the inability to identify a specific contribution of soy isoflavones to the cholesterol-lowering effects of soy protein," the final rule states. "Therefore, no additional benefit would result from restricting the claim to products having particular levels of isoflavones, or produced using particular methods of manufacture."

Comments suggesting food products that bear the soy protein health claim be allowed or required to state the isoflavone content on the label failed to offer persuasive evidence that consumers would find this information useful, FDA concludes.

Establishment of a 25 g per day level for a reduction in heart disease is supported by scientific literature demonstrating a consistent, clinically significant effect on total and LDL cholesterol levels, the agency says, disagreeing with the American Heart Association's suggestion that soy protein levels of 30 g to 50 g/day are necessary to produce clinically significant reductions in CHD (³ (Also see "Soy Protein Increased Daily Intake For Heart Disease Claim Urged By AHA" - Pink Sheet, 1 Feb, 1999.)).

Comments urging FDA to consider claims about other beneficial effects of soy protein on cardiovascular disease, other than lowering cholesterol, and on other diseases and health conditions, such as cancer, osteoporosis and menopausal symptoms, are beyond the scope of the current rulemaking, the agency says.