For the last twenty years, tofu has been all the rage. As people became increasingly educated about the dangers of dairy and dairy products, tofu became the viable substitute. However in a bizarre reversal of sorts, we have begun to discover that if a little of something is good, more of it is not necessarily better. “Tofu Shrinks Brain!” Not a science fiction scenario, this sobering soybean revelation is for real. But how did the “poster bean” of the ’90s go wrong? Apparently, in many ways – none of which bode well for the brain.
In a major ongoing study involving 3,734 elderly Japanese-American men, those who ate the most tofu during midlife had up to 2.4 times the risk of later developing Alzheimer’s disease. As part of the three-decade long Honolulu-Asia Aging Study, 27 foods and drinks were correlated with participants’ health. Men who consumed tofu at least twice weekly had more cognitive impairment, compared with those who rarely or never ate the soybean curd.
“The test results were about equivalent to what they would have been if they were five years older,” said lead researcher Dr. Lon R. White from the Hawaii Center for Health Research. For the guys who ate no tofu, however, they tested as though they were five years younger.
What’s more, higher midlife tofu consumption was also associated with low brain weight. Brain atrophy was assessed in 574 men using MRI results and in 290 men using autopsy information. Shrinkage occurs naturally with age, but for the men who had consumed more tofu, White said “their brains seemed to be showing an exaggeration of the usual patterns we see in aging.”
Phytoestrogens – Soy Self Defense
Tofu and other soybean foods contain isoflavones, three-ringed molecules
bearing a structural resemblance to mammalian steroidal hormones. White and his fellow researchers speculate that soy’s estrogen-like compounds (phytoestrogens) might compete with the body’s natural estrogens for estrogen receptors in brain cells.
Plants have evolved many different strategies to protect themselves from predators. Some have thorns or spines, while others smell bad, taste bad, or
poison animals that eat them. Some plants took a different route, using birth
control as a way to counter the critters who were wont to munch.
Plants such as soy are making oral contraceptives to defend themselves, says
Claude Hughes, Ph.D., a neuroendocrinologist at Cedars-Sinai Medical Center.They evolved compounds that mimic natural estrogen. These phytoestrogens caninterfere with the mammalian hormones involved in reproduction and growth – a strategy to reduce the number and size of predators.
Toxicologists Concerned About Soy’s Health Risks
The soy industry says that White’s study only shows an association between tofu consumption and brain aging, but does not prove cause and effect. On the other hand, soy experts at the National Center for Toxicological Research, Daniel Sheehan, Ph.D., and Daniel Doerge, Ph.D., consider this tofu study very important. “It is one of the more robust, well-designed prospective epidemiological studies generally available. . . We rarely have such power in human studies, as well as a potential mechanism.”
In a 1999 letter to the FDA (and on the ABC News program 20/20), the two
toxicologists expressed their opposition to the agency’s health claims for soy, saying the Honolulu study “provides evidence that soy (tofu) phytoestrogens cause vascular dementia. Given that estrogens are important for maintenance of brain function in women; that the male brain contains aromatase, the enzyme that converts testosterone to estradiol; and that isoflavones inhibit this enzymatic activity, there is a mechanistic basis for the human findings.”
Although estrogen’s role in the central nervous system is not well understood, White notes that “a growing body of information suggests that estrogens may be needed for optimal repair and replacement of neural structures eroded with aging.”
One link to the puzzle may involve calcium-binding proteins, which are
associated with protection against neurodegenerative diseases. In recent
animal studies at Brigham Young University’s Neuroscience Center, researchers found that consumption of phytoestrogens via a soy diet for a relatively short interval can significantly elevate phytoestrogens levels in the brain
and decrease brain calcium-binding proteins.
Concerns About Giving Soy to Infants
The most serious problem with soy may be its use in infant formulas. “The
amount of phytoestrogens that are in a day’s worth of soy infant formula equals 5 birth control pills,” says Mary G. Enig, Ph.D., president of the Maryland Nutritionists Association. She and other nutrition experts believe that infant exposure to high amounts of phytoestrogens is associated with early puberty in girls and retarded physical maturation in boys.
A study reported in the British medical journal Lancet found that the “daily
exposure of infants to isoflavones in soy infant-formulas is 6-11 fold higher on a bodyweight basis than the dose that has hormonal effects in adults consuming soy foods.” (A dose, equivalent to two glasses of soy milk per day, that was enough to change menstrual patterns in women. ) In the blood of infants tested, concentrations of isoflavones were 13000-22000 times higher than natural estrogen concentrations in early life.
Soy Interferes with Enzymes
While soybeans are relatively high in protein compared to other legumes, Enig says they are a poor source of protein because other proteins found in soybeans act as potent enzyme inhibitors. These “anti-nutrients” block the action of trypsin and other enzymes needed for protein digestion. Trypsin inhibitors are large, tightly folded proteins that are not completely deactivated during ordinary cooking and can reduce protein digestion. Therefore, soy consumption may lead to chronic deficiencies in amino acid
Soy’s ability to interfere with enzymes and amino acids may have direct consequence for the brain. As White and his colleagues suggest, “isoflavones in tofu and other soyfoods might exert their influence through interference with tyrosine kinase-dependent mechanisms required for optimal hippocampal function, structure and plasticity.”
High amounts of protein tyrosine kinases are found in the hippocampus, a
brain region involved with learning and memory. One of soy’s primary
isoflavones, genistein, has been shown to inhibit tyrosine kinase in the
hippocampus, where it blocked “long-term potentiation,” a mechanism of memory formation.