Chapter 122
Brain Supplements
The release of butyrate is not the only way the good gut bacteria interact with the brain. There is a large nerve—the vagus nerve—that runs directly from the gut to the brain. Certain Bifidobacterium and Lactobacillus probiotics fed to mice improve anxiety- or depression-related behavior and lower stress hormone levels, but only in animals with an intact vagus nerve. If the nerve is severed, the communication between gut bacteria and the brain is cut off as well, and the effect disappears. When the human vagus nerve is electrically stimulated, memory improves significantly, but a high-fiber diet may still be more pleasant than having an electrode implanted.
The microbiome also affects inflammation in the body. Differences in the gut flora of different people are largely attributable to different eating habits. Switching from a high-fiber, plant-based diet to a diet with animal products not only leads within a few days to a marked drop in butyrate levels, but also promotes the growth of pro-inflammatory bacteria. This matches cross-sectional data according to which people who eat more plant-based diets generally have an anti-inflammatory microbiome, whereas people who eat more animal-based diets tend to have more pro-inflammatory bacterial species.
Scientists were able to demonstrate the role of the bad gut bacteria in mouse fecal transplant studies. They replicated the same brain inflammation and dysfunction seen in mice fed lard by transferring the gut bacteria from those mice to others that had not eaten lard. As for humans, so far we have only been able to show that feeding mice feces from people with obesity impairs the animals’ memory, unlike feces from normal-weight individuals. If a bad gut flora contributes to cognitive dysfunction, could Alzheimer’s patients be treated with antibiotics to wipe out those bacteria? A pilot study with an antibiotic cocktail seemed to justify a more thorough investigation. Unfortunately, the follow-up study showed no significant effect.
There are over 20 randomized studies on probiotics and cognition in mostly healthy adults, and overall no benefit could be found. (In one study, probiotics impaired memory even more than placebos.) However, if you look only at five studies conducted in people with mild cognitive impairment or in the early stage of Alzheimer’s, taking various Lactobacillus and/or Bifidobacterium species for a period of twelve weeks appears to have boosted cognitive abilities more than in the control group.
Brain Supplements
In the last 20 years, Big Pharma has invested over half a trillion dollars in dementia treatment research, so far with little success. In light of that, many people turn to dietary supplements. A survey commissioned by the American Association of Retired Persons (AARP) showed that 36 percent of those over age 74 take brain supplements, to the tune of billions of dollars annually. I had never even heard of the top-selling one (probably because I don’t have a television): Prevagen.
Jellyfish Scam
Prevagen contains a protein from a bioluminescent jellyfish that the manufacturer claims “clinically proven to improve memory,” but not even a study by the manufacturer itself was able to show significant improvements in any of the nine measured cognitive tasks, after which the AARP accused the company of “deceiving millions of aging Americans.” But Prevagen may be more than a waste of money. The manufacturer was held to account for failing to report more than 1000 “adverse events” for which consumers had contacted the FDA. More on this embarrassing story at see.nf/prevagen.
A survey by Pew Charitable Trusts in 2019 found that more than half of respondents believed that, according to the FDA, dietary supplements must be tested for safety, which is not true. A study of dozens of dietary supplements sold as aids to boost cognitive performance found that most (71 percent) listed an ingredient on the label that was not actually in the product and, worse, that 38 percent contained ingredients that are not allowed in dietary supplements at all, such as banned drugs. Another study of a dozen supplements “for brain health” found that eight of twelve supplements were mislabeled (i.e., an ingredient promised on the label was missing), and ten of twelve were classified as adulterated (i.e., they contained undisclosed ingredients such as caffeine in a product explicitly labeled “decaffeinated”). Only one of the twelve supplements was actually third-party certified and contained the ingredients listed on the label.
Ginkgo
Ginkgo biloba is one of the most widely used dietary supplements for “brain health” and is taken by 2 percent of Americans. In recent decades, ginkgo extract has become one of the most commonly used herbal remedies for dementia. For details see see.nf/ginkgo, but bottom line, a review by the Cochrane network concluded: “The evidence that Ginkgo biloba has predictable and clinically significant benefit for people with dementia or cognitive impairment is inconsistent and unreliable.”
Ginseng, Rosemary, Sage, and Lemon Balm
Another herbal remedy that has been tested in randomized controlled trials is ginseng. Unfortunately, it failed in most studies. What about culinary herbs?
In Hamlet, Ophelia says rosemary is for remembrance, an idea that goes back to the ancient Greeks, for whom the fragrant herb “strengthens the brain … sharpens the mind, brings back lost memories, wakes the spirit …”. A study of cognitive performance showed that in a room scented with rosemary essential oil, even merely sniffing can have an effect (lavender essential oil or no smell at all, by contrast, did nothing). The participants’ performance boost was directly proportional to the amount of the rosemary preparation that—presumably via the lungs or nasal passages—entered the bloodstream. And what if you simply eat rosemary?
Older adults—average age 75—were given two cups of tomato juice either with half a teaspoon of powdered, dried rosemary (about the amount used in cooking) or with a whole teaspoon, two teaspoons, more than a tablespoon, placebo pills, or nothing at all. Compared to placebo, memory performance improved after the smallest dose but worsened after the highest, suggesting that more is not necessarily better.
Sage and lemon balm are two other herbs from the same botanical family that are valued in folk medicine for their purported benefit for the brain. Just hours after consuming a teaspoon of dried sage or a tea bag containing 1.6 grams of dried lemon balm, better memory performance could be observed. Note, however, that a study using rosemary, sage, and lemon balm extracts showed no memory improvement, meaning it may be better to go with the whole herb. Also note that these studies examined only the acute effect of single doses in healthy individuals. But are there any herbs or spices that actually improve cognitive abilities over a longer period?
Aromatherapy
The increased cognitive performance from sniffing rosemary essential oil was found in young, healthy volunteers, but what about those who really need it? A group of Japanese researchers put forward the adventurous thesis that certain scents could lead to a “rebirth of the nerves” in Alzheimer’s patients. Formulating that possibility as a hypothesis was sheer heresy 25 years ago. Everyone knew that dead neurons cannot be replaced. At least, that’s what we all learned until 1998.
Patients with end-stage cancer volunteered to have a special dye injected that new cells incorporate into their DNA. At autopsy, the scientists then went looking for glowing nerve cells—and there they were: in the brain, where months or days earlier there had been nothing. The new nerve cells proved that “the human brain retains the capacity for self-renewal throughout life.” The accompanying report bore the title “The Consolation of Human Neurogenesis.”