Spanish Sage Enhances Memory in Healthy Young Adults

Spanish Sage Enhances Memory in Healthy Young Adults
This aromatic herb may prove to be beneficial for Alzheimer’s victims as well
By Aaron W. Jensen, Ph.D.

euroscientists estimate that there are about 1 quadrillion (1,000,000,000,000,000) interconnections among the 100 billion or so neurons in the human brain. As staggering as that is, it pales in comparison to the number of neurotransmitter molecules that are zipping around in your head to make you a sentient creature. Each neuron-to-neuron connection, called a synapse, contains hundreds of millions of neurotransmitters. Multiply that by 1 quadrillion, and . . . well, it’s an awful lot.

With all that molecular messaging going on in your gray matter, it’s easy to understand (using your gray matter, of course) how things might eventually start to get a little disorganized, perhaps causing you to forget important things, such as the name of an acquaintance or a friend’s birthday. You might also start forgetting the items on your shopping list; or forgetting to collect the clothes from the dryer before they get wrinkled. (Luckily, forgetting to walk the dog is not a problem: he’ll remind you.)

Good Housekeeping Is Important

Normally, your brain maintains your memory function and other cognitive functions very efficiently. The good housekeeping is done at the molecular level, where it prevents disorder from building up and spinning out of control. Each time those huge swarms of neurotransmitters—such as acetylcholine—are released by a signal-transmitting neuron into a synapse to carry a message across the tiny junction (about one-billionth of an inch) to a signal-receiving neuron, the brain sends in a molecular “cleanup crew” to make sure the neurotransmitters don’t hang around too long and gum up the works.

In the case of acetylcholine, those cleaner-uppers are enzyme molecules called acetylcholinesterase. They cleave the acetylcholine molecules in two so they don’t swamp the acetylcholine receptors on the receiver neuron, which could cause a circuit overload. It’s just one of the many mechanisms the brain employs to ensure that neuronal signaling is tidy and exquisitely controlled.

Spanish Sage Helps Protect Acetylcholine

But sometimes things do go wrong, especially as we get older and our brains’ molecular mechanisms are impaired by wear and tear. One thing that can go wrong is the buildup of too much acetylcholinesterase in the synapses. If this occurs, neural signals may be impaired or short-circuited, because the neurotransmitters are unable to reach or adequately stimulate the target neuron. That means that brain messages—which may pertain, e.g., to memory, muscular function, or decision-making—don’t get completely processed.

As we get older, the brain’s housekeeping tends to become less efficient, and our mental faculties begin to fail. The typical symptom is memory loss, which can range from inconsequential (normal aging) to significant (mild cognitive impairment) to devastating and, ultimately, fatal (dementia, such as Alzheimer’s disease).

There are, however, ways to combat the fading of memory, and a simple herb, Spanish sage (Salvia lavandulaefolia), may help. That’s because this medicinal herb contains a variety of phytochemicals (plant-based compounds), several of which act as acetylcholinesterase inhibitors—compounds that interfere with the action of acetylcholinesterase, thus tending to preserve and protect your acetylcholine molecules. This enables your neural circuitry to operate more efficiently—meaning, among other things, that you probably won’t have to rely on your dog to remember to go for a walk (but he’ll remind you anyway).

College Students Recruited for Memory Tests

A group of neuroscientists in the United Kingdom has recently published three studies on the role of Spanish sage in memory and cognition, using the essential oil extracted from the herb. Their initial, provocative results demonstrate that this herb enhances memory even in healthy young adults (!) and may also be beneficial for older individuals who display the symptoms of Alzheimer’s disease.


Don't let your brain go down the drain.
In many cultures, the sage family of herbs has been used traditionally for a number of neurological problems, including depression, epilepsy, and age-related memory loss. Based on this rich history of use, the UK researchers set out to explore the benefits of Spanish sage, and they asked a tantalizing question: Could young adults with normal cognitive function actually improve their memory following ingestion of this herb?1

To find the answer, they recruited college students into two placebo-controlled, double-blind trials to identify the appropriate dose of Spanish sage oil for cognitive benefit. The first trial enrolled 20 students (aged 18–31, average age 20), who were given 50 µl (microliters), 100 µl, or 150 µl of sage oil or placebo before the cognitive tests were conducted. The second trial enrolled 24 students (aged 18–37, average age 23) and used doses of 25 µl or 50 µl of sage oil or placebo at each visit. Cognitive tests were performed immediately before administration of sage oil (baseline evaluation) and again at 1, 2 ½, 4, and 6 hours after supplementation.

In both trials, the students’ cognitive function was evaluated by standardized testing measures, including immediate word recall and delayed word recall. To test immediate word recall, students were shown 15 commonly used words on a computer screen for 1 second each and were allowed 60 seconds to write down as many of the words as they could remember. Twenty minutes later, to test delayed word recall, they were again directed to write down as many of the original 15 words as they could remember.

Sharp Young Minds Made Even Sharper

In the first trial, the most robust memory enhancement was observed for the 50-µl dose at the 1-hour and 2 ½-hour time points, with improved performance on both immediate word recall and delayed word recall. A smaller benefit was observed on both cognitive tests following administration of the 100-µl dose, but only at the 2 ½-hr time point. No benefit was observed for the highest dose of 150 µl. (This pattern demonstrates an important principle regarding supplementation: too much of a good thing may be no good at all. Sometimes it may even be harmful.)

The second trial yielded similar results for the 50-µl dose, for which the greatest cognitive benefit was again observed 1 hour after supplementation. The lower dose of 25 µl did not reveal a statistically significant improvement. In this particular group of students, the benefit associated with the 50-µl dose lasted longer—up to 4 hours—but was specific to immediate word recall and was not beneficial for delayed word recall. No adverse reactions were associated with any of the doses of Spanish sage oil in either trial.

It’s important to remember that these trials were conducted on healthy young adults with normal cognition. Even so, supplementation with 50 µl of Spanish sage oil produced meaningful improvements in cognition in just 1 hour. That’s a pretty impressive result for a modest little herb!

Are There Benefits for Older Folks Too?

It’s possible that Spanish sage may also be of benefit in older individuals with Alzheimer’s disease (AD), as suggested by the UK research group’s preliminary 6-week, open-label trial with 11 patients (aged 76–95) diagnosed with probable mild to moderate AD.2 Patients participating in the trial were given one 50-µl capsule of Spanish sage oil in the morning for the first week; 2 capsules (morning and evening, 100 µl total) for the second week; and three capsules (morning, noon, and evening, 150 µl total) for the third through sixth weeks.*


*This type of “dose escalation” study is common in AD trials, in which a small dose is escalated over succeeding weeks to the final dose, to acclimate the patients to the treatment and guard against gastrointestinal distress. This approach is usually necessary with acetylcholinesterase inhibitors.


The patients were given a standard cognitive function test at the outset of the study and again after 6 weeks of treatment. The results were negative: no change. It would be premature to make much of these results, however, as this trial was not designed to monitor neurological progress in the patients. Rather, it was conceived as a tolerability trial to determine whether Spanish sage oil would be well tolerated by probable AD patients. In that sense, it was a success, as the researchers found no adverse effects following supplementation, except for an increase in blood pressure in two patients with a history of hypertension.


Supplementation with 50 µl of
Spanish sage oil produced
meaningful improvements in
cognition in just 1 hour. That’s a
pretty impressive result!


There were nonetheless some interesting trends that emerged from the study, namely, that there was a reduction in neuropsychiatric symptoms and an improvement in attention. While this is not the definitive work on this topic, the researchers were sufficiently encouraged by the initial results that they believe a long-term, placebo-controlled trial to further explore the possible benefits of Spanish sage oil in AD patients is warranted.


Spanish sage (Salvia lavandulaefolia)
How Does Spanish Sage Work?

Different species of sage plants have been observed to have many beneficial properties, including anxiolytic (calming), antioxidant, estrogenic, antidepressive, and anti-inflammatory properties. To that list, we can now add the effect of cognitive enhancement, thanks to the ability of Spanish sage to inhibit acetylcholinesterase activity.

In fact, this species of sage contains multiple acetylcholinesterase inhibitors, including 1,8-cineole (by far the most potent component), alpha-pinene, and caryophyllene oxide.3 These compounds limit the degradation of acetylcholine and preserve its function in the neural synapses. More than any single ingredient in Spanish sage, however, it may be the synergistic effects among various combinations of ingredients in the oil that provide the greatest benefit. For example, the UK researchers found that when 1,8-cineole is combined with either alpha-pinene or caryophyllene oxide, the combined effect is greater than the sum of its parts—the definition of synergism.

Lemon Balm Is Complementary to Spanish Sage

Another herbal product, lemon balm (Melissa officinalis), has also been found to improve certain aspects of memory and mood in healthy young adults. It does so through a mechanism complementary to that of Spanish sage: it stimulates the brain’s acetylcholine receptors. The net result of the combined action of these two herbal products is thus to enhance both the level and the activity of acetylcholine molecules in the brain.

This action may serve not only to enhance cognitive function but also to calm the nervous agitation that often accompanies dementia. Indeed, there is clinical research suggesting that lemon balm may be beneficial in these regards and may find application in individuals afflicted with Alzheimer’s disease. (See “Can High-Quality Lemon Balm Ease Dementia?” in Life Enhancement, January 2004.)

An Abundance of Sages

Salvia is a large genus containing about 500 species of sage plants throughout the world. Only a few of these, however, have commercial, medicinal, or culinary value. One type of Chinese sage (Salvia miltiorrhiza) has been used for a thousand years in traditional Chinese medicine to treat cerebrovascular disease and is now known to contain acetylcholinesterase inhibitors, which are the preferred agents for treating Alzheimer’s disease.

Common or garden sage (Salvia officinalis) has been the subject of research for its possible use as a treatment for Alzheimer’s; it is best known, however, as a kitchen herb for use with foods such as sausages, meats, and traditional Thanksgiving stuffing. Wild sage (Salvia lyrata) is found mainly in the eastern United States, where it’s used as a folk remedy for warts. A certain sage found in Mexico, Salvia divinorum, has hallucinogenic properties and is chewed, drunk, or smoked by Indian shamans in some traditional rituals.

Clearly not all sages are the same. Although they may look similar, each species is biochemically distinct, with a unique combination of compounds. Such is the wonder of DNA—even small changes in genetic makeup can translate to large differences among species. For example, Spanish sage (Salvia lavandulaefolia) contains active acetylcholinesterase inhibitors but very low levels of thujone, a neurotoxic compound found in much higher amounts in many other sage species.

Become a Sage

If you had a buck for every synaptic event that occurred in your brain while you read this sentence, you could single-handedly pay off the national debt (get a receipt!). That should give you an appreciation for the sheer volume of neural activity that goes on in your brain all the time. But although your brain is incredibly efficient in its functions, it does have occasional lapses—even if you’re still a long way from old age. Giving it some Spanish sage might be just the ticket for keeping those molecular mechanisms humming. That would be a sage thing to do.

References

  1. Tildesley NTJ, Kennedy DO, Perry EK, Ballard CG, Savelev S, Wesnes KA, Scholey AB. Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers. Pharmacol Biochem Behavior 2003;75:669-74.
  2. Perry NSL, Bollen C, Perry EK, Ballard C. Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behavior 2003;75:651-9.
  3. Savelev S, Okello E, Perry NSL, Wilkins RM, Perry EK. Synergistic and antagonistic interactions of anticholinesterase terpenoids in Salvia lavandulaefolia essential oil. Pharmacol Biochem Behavior 2003;75:661-8.


Dr. Jensen is a cell biologist who has conducted research in England, Germany, and the United States. He has taught college courses in biology and nutrition and has written extensively on medical and scientific topics.

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