An Explanation of "Brain Aging and Midlife Tofu Consumption," (L.R. White, et al., Journal of the American College of Nutrition 2000; 19: 242–255; abstract at the end of this treatise)

Copyright ã 2003, James Michael Howard, Fayetteville, Arkansas, U.S.A.

The findings of White, et al., may be explained as premature decline of production of the major adrenal steroid hormone, dehydroepiandrosterone (DHEA). Tofu (soy, phytoestrogens) stimulates DHEA production. This stimulation acts on a finite capability of DHEA production during the human life span which peaks around the age of twenty to twenty-five and then declines to very low levels in old age. This Stimulation of DHEA by tofu during "midlife" inappropriately advances the natural decline of DHEA of old age and the consequences of loss of DHEA of old age. I am suggesting the tofu is advancing the decline of DHEA of old age. (In the following chart, the black curve is the "normal" production of DHEA during the human life span. The red curve is a "generic" curve of anything which causes DHEA production to increase and then results in reduced DHEA in cases such as this. This eventually decreases the overall time of production of DHEA during the life span.)


 It is my hypothesis that DHEA was selected by evolution because DHEA optimizes replication and transcription of DNA. In fact, I suggest DHEA was fundamental in the evolution of mammals and large brains ("Hormones in Mammalian Evolution," Rivista di Biologia / Biology Forum 2001; 94: 177-184 ). I think DHEA is critical to growth and development and maintenance of our brains. Therefore, any substance or behavior which affects the production of DHEA also affects our brains. Of importance to this explanation of the effects of tofu is the other major adrenal steroid hormone, cortisol. It is my hypothesis that cortisol evolved as the major antagonist of DHEA function.

The phytoestrogens found in tofu are known to "markedly" increase DHEA production while decreasing cortisol production; the hypothesis is that cortisol synthesis is "shunted" toward DHEA synthesis (J Clin Endocrinol Metab. 1999; 84: 2443-8). So, tofu increases DHEA and, at the same time, decreases the major DHEA antagonist, cortisol. If the production of DHEA over the life span is finite, this should shorten the time of DHEA production. If a person started consuming tofu in "midlife," this should increase DHEA and hasten time of reduced DHEA production and the consequences of low DHEA. That is, this should accelerate the onset of the effects of loss of DHEA; this should accelerate old age. I suggest the loss of DHEA results in declines we describe as "old age."

White, et al., point to increased "brain atrophy" and use hippocampal decline and enlarged ventricles as examples of the negative effects of tofu consumption at midlife. The loss of DHEA of old age has been connected to hippocampal reduction and ventricle enlargement: "In elderly subjects, particularly if demented, the mean serum dehydroepiandrosterone sulfate (DHEAs) levels throughout the 24-hour cycle were significantly lower than in young controls. A significant reduction of the hippocampal and temporal volume and an enlargement of the lateral ventricles were found in aged subjects, these changes being significantly related to subjects' age." (Dement Geriatr Cogn Disord. 2000; 11: 90-9). Since tofu stimulates DHEA production, tofu accelerates the onset of the end of production of DHEA. In this case, tofu is accelerating the signs and symptoms of old age, such as damage to the hippocampus and ventricle enlargement.

The effect of consumption of tofu at midlife was increased in men, though the effect was still present in women. I suggest testosterone reduces overall availability of DHEA, especially when DHEA production is limited ("Androgens in Human Evolution," Rivista di Biologia / Biology Forum 2001; 94: 345-362 .) Therefore "male gender" should exacerbate the characteristics of decline of old age: "Results indicated that: (1) after age 60, cerebral atrophy, polio- and leuko-araiosis doubled and cerebral perfusion decreased, with marked individual variations; (2) risk factors independently accelerating cerebral atrophy and cortico-subcortical perfusional declines included [transient ischemic attacks] TIAs, hypertension, smoking, hyperlipidemia, excessive alcohol consumption and male gender; (3) progressive leuko-araiosis correlated directly with cortical atrophy and cortical perfusional declines. We posit that: (1) cerebral atrophy and degenerative changes result from neuronal shrinkage and/or loss, which are accelerated by TIAs, hypertension, smoking, hyperlipidemia, excessive alcohol consumption and male gender; (2) accelerated cerebral atrophic and degenerative changes identified by neuroimaging should be considered as markers for depleted neuronal synaptic reserves, which predispose to cognitive declines." (J Neurol Sci. 1997; 152: 39-49). The effect of tofu in women is reduced because they produce less testosterone.

It is my hypothesis that testosterone ultimately, adversely affects the availability of DHEA. This should shorten the time of useful DHEA production, therefore, shorten the time to old age and its consequences. Men die earlier than women. I also suggest that drugs are "attractive" and "addictive" because they stimulate DHEA production. All of these would have the same effect as I have just suggested for tofu in men at midlife. Again, I suggest the explanation of the findings of White, et al., is tofu, by stimulating DHEA, accelerates the decline of DHEA of old age and its consequences. Please note that it is my hypothesis that cancer may be triggered by low DHEA; please see "An Explanation of Cancer and the Increase in Cancer." Before you totally condemn soy because of the findings that caused me to write this, please note that the many health benefits attributed to soy may be real because soy increases DHEA and reduces cortisol. The simple problem is that this shortens the time to low levels of DHEA.


Here is the abstract of L.R. White, et al., Journal of the American College of Nutrition 2000; 19: 242–255:


"Objective: To examine associations of midlife tofu consumption with brain function and structural changes

in late life.

Methods: The design utilized surviving participants of a longitudinal study established in 1965 for research

on heart disease, stroke, and cancer. Information on consumption of selected foods was available from

standardized interviews conducted 1965–1967 and 1971–1974. A 4-level composite intake index defined

"low-low" consumption as fewer than two servings of tofu per week in 1965 and no tofu in the prior week in

1971. Men who reported two or more servings per week at both interviews were defined as "high-high"

consumers. Intermediate or less consistent "low" and "high" consumption levels were also defined. Cognitive

functioning was tested at the 1991–1993 examination, when participants were aged 71 to 93 years (n 5 3734).

Brain atrophy was assessed using neuroimage (n 5 574) and autopsy (n 5 290) information. Cognitive function

data were also analyzed for wives of a sample of study participants (n 5 502) who had been living with the

participants at the time of their dietary interviews.

Results: Poor cognitive test performance, enlargement of ventricles and low brain weight were each

significantly and independently associated with higher midlife tofu consumption. A similar association of midlife

tofu intake with poor late life cognitive test scores was also observed among wives of cohort members, using

the husband’s answers to food frequency questions as proxy for the wife’s consumption. Statistically significant

associations were consistently demonstrated in linear and logistic multivariate regression models. Odds ratios

comparing endpoints among "high-high" with "low-low" consumers were mostly in the range of 1.6 to 2.0.

Conclusions: In this population, higher midlife tofu consumption was independently associated with

indicators of cognitive impairment and brain atrophy in late life."