On Your Mind: Strawberry Fields For Memory

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volume 10 number 11 january 2012

By Benjamin V. Treadwell, Ph.D.

Most of us admire the plant kingdom's magnificent natural beauty and variety, from the awesome giant redwoods to delicate tropical orchids. Many take a personal interest, too, cultivating and caring for plants as if they were family.

This high regard makes sense. Members of the animal kingdom, humans included, cannot survive without the many essential nutrients plants supply. Scientific discoveries continue to underscore their importance to our health.

This issue of the Juvenon Health Journal will introduce plant nutrients that are active in protecting our nervous system and improving memory. The story will continue in our next issue, which will cover plant foods containing genetic material capable of entering our body's cells to affect our health, even our state of mind. All illustrating how plants and animals truly are interconnected in both obvious and, perhaps, unexpected ways.

Brain Fade
One of the positive things about getting older is the accumulation of knowledge from experience. Unfortunately, age also takes a toll on the health of our organs. For the brain, that can mean loss of mental sharpness, as well as a noticeable decline in memory and awareness of our surroundings (cognition).

Scientists have put forth many hypotheses to explain this decline. One includes an age-associated decrease in the supply of nutrients. Another theory speculates that memory decline may be due to reduced circulation of blood to the brain. Studies, demonstrating that aerobic exercise (getting the heart pumping and blood flowing) improves brain health, seem to support this explanation. (See Juvenon Health Journals, Volume 10, Number 2, "The Aging Brain: Moderate Exercise For Maximum Memory," and Volume 9, Number 12, "Exercise: Could More Be Better As We Get Older?".)

Research has also shown plant-derived supplements, such as resveratrol, can improve blood-to-brain circulation and, consequently, memory in humans. (See Juvenon Health Journal, Volume 9, Number 4, "Resveratrol: New Evidence For A Human Health Benefit.") However, recently, a plant nutrient with structural similarities to resveratrol joined the list of those with the potential to increase brain function.

Fisetin Fact-finding
The nutrient is fisetin, a polyphenol (naturally occurring chemical) and flavonoid (antioxidant plant pigment compound). The highest concentrations of fisetin are found in strawberries, although it's present in a number of plants.

Over the last few years, exciting animal studies have shown fisetin may help protect the brain's delicate architecture, as well as boost memory and cognition. One study with mice, for example, produced promising results related to fisetin's effect on learning/memory.

The memory - learning ability of the fisetin-fed mice improved by an amazing 50%!

The memory - learning ability of the fisetin-fed mice improved by an amazing 50%!

The research team followed a common protocol for measuring a rodent's memory: a water maze fitted with a submerged platform for resting. One group of mice (control) was fed normal mouse chow. A second group (experimental) ate chow that contained fisetin.

The team placed the mice in the water maze and recorded the time it took each one to find the platform. During the initial exposure, there was no significant difference between the times for the control and experimental groups.

However, the researchers then retested both groups of mice in the water maze after a 24-hour rest period. The fisetin group took half the time to find the platform. In other words, during this 24-hour period, the memory of the mice taking fisetin saw their memory/learning ability dramatically improve (by an amazing 50%!), compared to the controls.

Naturally, the investigators next question was: what mechanism in the brain makes fisetin so effective?

Sensitivity Training
Over 40 years ago, in early work on the enigma of learning and memory, Tere Lomo, from Oslo, Norway, made an important discovery while studying the hippocampus (center for learning and memory) of a rabbit brain. If he applied an electrical pulse to a neuron connected in a circuit to a series of neurons (neuronal circuit), it evoked a response that could be measured, as the pulse traveled from one neuron to another in the electrical circuit.

Even more impressive was his discovery that the intensity of the pulse was important. The greater the magnitude of the initial electrical stimulation, the easier it was to activate the electrical circuit with subsequent, much smaller electrical pulses.

This is called long-term potentiation (LTP), which simply means the neuronal electrical circuit is sensitized and functions like a "trigger finger" with subsequent stimulation. (For more on LTP, see Juvenon Health Journal, Volume 10, Number 6, The Aging Brain: Why We Forget And What Might Help.") This sensitized state persists for long periods and forms the basis of memory and learning.

To put this concept in the context of human memory, bring an experience to mind that left a strong impression on you. Did you remember it vividly and quickly? Now you know why. The original event evoked major, brain-produced electrical stimulation. It sensitized the neuronal circuit, allowing the event to be relived with ever-so-slight stimulation, like simply seeing something or someone present at the time of the initial event.

Learning also produces electrical pulses in the brain, which modify its structural architecture. Pick-up a book you read in the past. The neurons in the brain initially activated by its content are sensitized, readily bringing what you learned to mind as a basis for learning more.

Interestingly, all neuronal circuits are not created equal. From one brain to another, some are more readily sensitized for increased LTP. (Does this make some people smarter than others?) But there's hope for those with shorter long-term potentiation. Research is beginning to identify natural nutrients, as well as other methods, that may improve it, in effect making us smarter!

Fisetin-LTP Connection
Which leads us back to the "smarter" fisetin-fed mice. According to recent work from the same group of investigators, and supported by other laboratories, Long Term Potentiation may be the key. Their experiments show that fisetin seems to improve the sensitization of neurons involved in memory formation.

The latest research also indicates fisetin has a number of additional effects on brain health and function. For instance, the nutrient activates genes responsible for the production of the potent antioxidant glutathione. It also slows the production of inflammatory molecules known to be destructive to neuronal electrical circuits.

In other words, fisetin seems to be acting on numerous biochemical pathways, as well as affecting long-term potentiation, to improve memory and learning.

On Our Mind
Maintaining a sharp memory, wit, and ability to learn is certainly critical to our quality of life. As mentioned earlier, aerobic exercise seems to make a big difference. It gets the blood flowing to supply nutrients to the organs of the body, including the brain.

But what about the nutrients themselves? For practically as long as we can remember, nutritionists have been telling us that plants - vegetables, fruits, nuts, seeds - should be a staple of our diet. We continue to discover the details of how the nutrients they provide benefit us, specifically our mental faculties.

Some theorize this is an evolutionary phenomenon. As the animal kingdom, humans included, co-evolved with plants, we became dependent on them to supply bits and pieces of genetic information. The effects of flavonoids, like fisetin and resveratrol, which we can no longer produce, appear to be consistent with this concept.

In any case, the connection between plants and animals is pretty fascinating. Not only historically, but at the level of epigenetics, the influence your environment and choices have on your genetic code. In fact, the next Health Journal may "shock" you with more of the epigenetics story.

To be continued…

Dr. Treadwell
answers your questions.

question: Recently, there have been articles saying that we don't need to be taking vitamins in addition to a balanced diet. What do you think? After just reading the e-mail that you sent, I can imagine that would not be your position, especially as we all age. I'm looking squarely at 60! Thanks -- A

answer: I think it's fair to say that at least some of us may need more nutrition than our diet is providing. The evidence in support of taking vitamins and nutritional supplements for optimal health seems substantial.

For every article reporting little or no positive effect from supplementing with vitamins, there are even more studies demonstrating the complete opposite, conducted by laboratories around the world. In practice, health professionals routinely order tests to monitor blood levels of vitamins and minerals, then recommend health supplements as indicated.

Factors other than an "unbalanced" diet can also cause deficiencies. As you mentioned, they include aging. Older people, for example, are often deficient in Vitamin B-12. Peer-reviewed research indicates they may benefit from supplementing. Research has connected low levels of B-12 to senior health concerns like atherosclerosis and neurodegenerative conditions such as Alzheimer's disease.

Recently, you may have also read about the "dangers" of some vitamins. One seems to contribute to cardiovascular disease, while another may increase the incidence of stroke. Pretty shocking until you realize that flawed experimental protocols or uneducated interpretations are often behind these kinds of conclusions.

In other words, it's best to take what you see in the media with a grain of salt (unless you're hypertensive). Hedge your bets with exercise and a healthy diet of fruits, vegetables, legumes, fish, olive oil, and a minimum of high-fat, high-sugar, low-food-value choices.

When selecting supplements, be skeptical. Rely on trusted sources, including your health professional. And keep in mind that genetics, as well as stress, also contribute to your vitamin needs. These factors vary from person to person, making it nearly impossible to prescribe a vitamin (or no-vitamin) regimen that applies to everyone.

No wonder the RDA is in constant flux! Current and future research will provide us with the tools to examine parameters of health on a more personal level, allowing for nutrient recommendations tailored to the individual.

Send your questions to AskBen@juvenon.com.
For more questions and answers, click here.

Dr. Benjamin V. Treadwell is a former Harvard Medical School professor and member of Juvenon’s Scientific Advisory Board.

Research Update
After identifying a small molecule in strawberries that may help maintain aging brain function on multiple levels, investigators from the Salk Institute for Biological Sciences in La Jolla, CA examined this molecules effects in mice and rats. Their findings appeared in a Genes & Nutrition article: "Modulation of multiple pathways involved in the maintenance of neuronal function during aging by fisetin."

Fisetin, is a plant flavonoid, found at highest concentrations in strawberries. Fisetin acts directly as an antioxidant, helping maintain mitochondrial function in the presence of oxidative stress. It can increase the levels of a major intracellular antioxidant, glutathione, and also acts as an anti-inflammatory.

To determine how fisetin may help reduce age-related learning and memory deficits, the research team conducted rodent model experiments. In one study, they fed half a group of mice food containing fisetin and the other half (the controls) the same food without the flavonoid.

The two groups navigated a water maze with a submerged "rest" platform that would allow them to avoid becoming exhausted from swimming. There were visual cues to help them find it. The time it took each mouse to locate the platform was recorded.

To measure learning, both groups ran the water maze again 24 hours later. The fisetin-fed group was much faster than the controls, finding the platform in half their original times. In other words, they demonstrated a significant advantage in their ability to remember/learn.

Intrigued by what seemed to be a fisetin-induced improvement in learning ability, the researchers designed another experiment to help determine the mechanism(s) behind it. This time the study focused on the memory center of the brain, the hippocampus. The investigators hypothesized that fisetin facilitates the molecular basis for learning and memory: long-term potentiation (LTP).

LTP is the term for helping two neurons transmit electrical charges and improving sensitivity to electrical stimuli. A strong external stimulus improves the synapse's strength, sensitizing it to a full response with subsequently less intense stimuli. This effect can last for a long period of time, hence long-term potentiation.

To test their theory, the research team incubated sections of tissue from the rats' hippocampi in a medium with or without (control) fisetin. They stimulated the sections with electrical pulses and recorded the responses. The hippocampal tissue incubated in the presence of fisetin was more responsive to minimal electrical stimulation than the control tissue.

The results support the team's hypothesis. They demonstrate that fisetin increases the sensitivity of the biochemical pathways involved in inducingthe memory-important brain activity, LTP. (Additional studies by this group have also shown that fisetin acts on multiple biochemical pathways to improve brain health and function.)

Read abstract here.

This Research Update column highlights articles related to recent scientific inquiry into the process of human aging. It is not intended to promote any specific ingredient, regimen, or use and should not be construed as evidence of the safety, effectiveness, or intended uses of the Juvenon product. The Juvenon label should be consulted for intended uses and appropriate directions for use of the product.