SOY AND COGNITIVE FUNCTION IN AGING ADULTS

Life expectancy has risen steadily due to innovations in medicine and improved living standards.¹ With an extended lifespan, it is increasingly important to understand how these additional years of life can be spent in good health. As discussed by Oschwald et al.,² cognitive health is of high importance for aging healthily³ with a substantial impact on one’s ability to complete tasks of independent living⁴ such as medication adherence,⁵ telephone use, financial management, or nutritional choices.⁶

Cognition is defined as the mental action or process of acquiring knowledge and understanding through thought, experience, and the senses.⁷ There is intriguing but speculative evidence that certain dietary patterns and specific foods and dietary components can slow age-related decline in cognitive function.^8-10 Is soy one of these foods? Increasingly, the evidence suggests that it may be; early on, that conclusion certainly did not appear to be case.

Of the various health outcomes being investigated in relation to soy intake, cognitive function took center stage in the year 2000 with publication of results from the Honolulu-Asia Aging Study (HAAS). This prospective epidemiologic study, which began in 1965, found that higher midlife tofu consumption was independently associated with indicators of cognitive impairment and brain atrophy later in life.¹¹ The study involved men, but a post-hoc analysis showed that the results also applied to the spouses of the men in this study. The man’s tofu intake was used as a surrogate for his wife’s intake. The operating hypothesis at the time was that isoflavones in soy were exerting an anti-estrogenic effect in the brain. At the turn of the century, there was growing speculation that estrogen might reduce risk of cognitive impairment in menopausal women.¹²

There are several important limitations to the HAAS. For one, the primary outcome was coronary heart disease; not cognitive function. The latter outcome was added long after the study began. In addition, the food frequency questionnaire (FFQ) included questions about only 26 foods, which pales in comparison to modern FFQs which typically include more than 100 items. Also, questions about tofu intake varied over the course of the study so a new tofu intake category had to be created.

In contrast to the HAAS, several small clinical studies published in the early 2000s suggested soy and soybean isoflavones may have cognitive benefits.^13-16 However, clinical research published over the next several years produced very mixed results. For example, trials involving postmenopausal women published in 2005¹⁴ and 2006¹⁷ showed benefits, but trials published in 2004¹⁸ and 2007¹⁹ did not. 

Importantly, also in contrast to the HAAS, a U.S. cross-sectional study involving middle-aged Asian women published in 2006²⁰ and a cross-sectional study from Hong Kong involving older men and women published that same year²¹ found no relationship between isoflavone intake and cognitive function. It is fair to say that except for the results of the HAAS, the observational and clinical evidence suggested soy intake and/or isoflavone exposure had either no effects on, or favorably affected, cognitive function. 

However, in 2008, the controversy ignited by the HAAS was refueled by the results of a cross-sectional study from Indonesia involving men and women aged 52-98. This study found high tofu consumption was associated with worse memory, whereas high tempeh consumption was independently related to better memory, particularly among participants over 68 years of age.²² The authors suggested the contrasting effects between tofu and tempeh might be due to the adverse effects of isoflavones in tofu or the presence of formaldehyde, which is illegally used by some street vendors as a preservative. It was also suggested that the high folate content of tempeh produced as a result of fermentation could have led to the observed beneficial effects. 

Those mechanistic explanations did not have much support. Furthermore, in 2011, a follow-up study to the Indonesian cross-sectional study²² found positive linear associations of weekly tofu and tempeh consumption with immediate recall, which were significant in those with an average age of 67 years.²³ In addition, among those with an average age of 80, the earlier reported negative association of tofu with immediate recall was no longer significant.²³ 

In 2014, after comprehensively reviewing the clinical and epidemiologic data, Soni et al., ²⁴ concluded that “… the evidence to date is not sufficient to make any recommendations about the association between dietary intake of soy isoflavones and cognition in older adults.” Given the amount of research upon which this assessment was based, this author’s perspective at that time was that it was unlikely additional research would change the current scientific consensus any time soon. However, research produced in the past 6 years warrants a reevaluation of that perspective.

In 2020, a meta-analysis that included 16 randomized clinical trials involving 1,386 participants, with a mean age of 60, found that soy isoflavones improve overall cognitive function and memory.²⁵ This conclusion concurs with a meta-analysis published in 2015²⁶ and a systematic review of the clinical data published in 2017.²⁷ In addition, a Taiwanese cross-sectional study published in 2018, found soy intake was associated with a decreased risk of cognitive impairment.²⁸ Finally, Zajac and colleagues²⁹ found that in contrast to whey protein, soy protein improved reaction time and reasoning speed in postmenopausal women, although no improvement was noted in men.

In summary, the available data still do not allow for definitive conclusions to be made about the cognitive benefits of soy. On the other hand, the evidence points in the direction of benefit. Finally, the initial concern about adverse cognitive effects raised by the publication of the HAAS has not been supported by subsequently published research.

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