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Sage leaves made in extract linked with increased memory

Restore Cognitive Funtion

In people over age 64, a unique sage extract increased memory performance nearly 60% and improved attention by about 2.5-fold compared to a placebo.

Scientifically reviewed by Dr. Gary Gonzalez, MD, in October 2024. Written by: Harry Fulton.

Starting around age 30, we begin to notice short-term memory deficits.

This may happen when after taking a drug, we have no immediate recall if we actually swallowed the pill.

As people advance past 60 years, they often rely on "pill organizers" to ensure medications are taken on schedule.

Short-term memory decline is a troubling aspect of brain aging.

A clinical study evaluated a standardized sage extract compared to placebo in adults over age 64.1

Within hours of ingesting this sage extract, memory performance increased nearly 60%, along with an approximate 2.5-fold improvement in attention.

When this sage extract was tested in the C. elegans model of aging, there was a 12% increase in lifespan,2 attributable in part to increased expression of insulin signaling genes that have been tied to enhanced longevity.3

Meticulous research has now identified how this sage extract enhances cognitive function in humans and increases lifespan in a validated model of aging.

What you need to know

  • Sage has been recognized for its numerous health benefits for centuries.
  • Numerous beneficial compounds in sage enhance and protect brain function by several complementary mechanisms.
  • Low levels of the neurotransmitter acetylcholine are associated with age-related cognitive dysfunction and dementia. Like medications used to treat dementia, sage boosts levels of this important neurotransmitter in the brain.
  • A proprietary sage extract with unique properties that have not been identified in other sage formulations18 has demonstrated beneficial effects on cognitive performance and cerebral blood flow in humans, as well as boosting longevity related genes in a C. elegans animal model.
  • Sage can work together with other brain healthy nutrients to maximize brain function and prevent age-related cognitive decline.

Sage Extracts Protect the Brain

Foods considered as a part of the Mediteranian diet

Age-related mental decline, including mild cognitive impairment, is a normal part of brain aging.

Many factors lead to dwindling cognitive functions.

Readers of this magazine take steps to circumvent mind-robbing pathologies, such as maintaining cerebral circulation and keeping homocysteine in safe ranges.

Clinical data on a novel sage extract indicates additional protective effects.

Role of Acetylcholine on Short-Term Memory

Neurotransmitters are compounds brain cells use to communicate with one another.

Acetylcholine is a neurotransmitter critical for memory, attention, and reasoning. With aging and neurodegenerative disorders, acetylcholine levels can be depleted.4

This decrease in acetylcholine is responsible for many age-related deficits, including poor memory and the inability to pay attention to tasks.5

Currently available drugs can improve dementia symptoms by boosting brain levels of acetylcholine. This has been demonstrated to reduce the cognitive deficits in the short term.6,7

In a recent review of several trials in Alzheimer's patients, treatments that boost acetylcholine are associated with more than 20% lower overall mortality.7

These treatments work to increase acetylcholine in the brain by blocking activity of an enzyme that degrades it. This enzyme is called acetylcholinesterase .

Sage extracts inhibit this same enzyme and boost acetylcholine levels. Significant improvements in cognitive functions have been demonstrated in human studies.1,8-11

Boosting Brain Performance

Acetylcholine is one of the most common neurotransmitters and its functions are critical for normal cognition, including memory, attention, and reasoning.

Unfortunately, acetylcholine is one of the hardest hit in aging and Alzheimer's disease.4 Brain cells that use acetylcholine are some of the most profoundly affected.

Most modern medical treatments for dementia attempt to improve symptoms by boosting levels of acetylcholine, which has demonstrated the ability to reduce the cognitive deficits and enhance brain function in the short term.6,7

These drugs increase levels of acetylcholine by blocking the activity of the enzyme that degrades it, called acetylcholinesterase.

Many studies have now confirmed that sage also exhibits this ability, boosting levels of acetylcholine in addition to all of its preventative properties.1,3,8-11

This may explain why sage can cause almost immediate augmentation of brain function.

Pharmaceutical approaches to treating dementia mostly address acetylcholine. The multiple mechanisms of sage in the brain can help boost current cognitive function as well as prevent future progression of age-related dysfunction.

Growing New Brain Cells

Foods considered as a part of the Mediteranian diet

Neurotrophins are proteins produced in the body that help maintain brain function. They support survival of brain cells and encourage neurogenesis, a process that replenishes and repairs brain cells.12

Normal aging leads to lower neurotrophins levels, which is implicated in the progression of cognitive impairment and Alzheimer's disease.13

Sage helps to support healthy levels of neurotrophins, boosting their levels even in the presence of cellular stress and injury.10

The ability of sage extract to support neurotrophins can help protect against future loss of functionality and dementia.

Measuring Superior Biological Activity

Intensive chemical analysis of this novel sage extract demonstrates that it has a unique chemical fingerprint compared to other sources of sage.18

Furthermore, this proprietary sage extract has superior biological activity compared with other sage sources and cognitive drugs when tested by Chronoscreen™ assay in C. elegans.2,19

Chronoscreen™ is a patented technology that can evaluate the effect of nutrients and drugs on lifespan in a whole organism.

Life Extension has closely collaborated with scientists at a group called Sibelius to uncover the specific mechanisms of action of this proprietary sage extract. The goal has been to more precisely identify how this particular sage extract enhances memory and attention in humans.

This Chronoscreen™ assay revealed the surprising finding of a 12% lifespan increase in the C. elegans model, an effect not found with other sage extracts.2

Oxidative Stress and Inflammation

Female scientist reading

Most age-related diseases are at least partially tied to oxidative stress and inflammation. Age-related deterioration of brain function is no exception.

Sage contains compounds that scavenge harmful free radicals and reduce the deleterious effects of inflammation.10

In a rat model of diabetes, one study showed that sage limited oxidative damage and boosted oxidant-reducing defense systems. This resulted in reversal of learning and memory deficits.14

Complementary Nutrients for Brain Health

Mitochondrial cell

While sage provides protection and enhancement of brain health by several means, there are other nutrients which can help maximize nervous system function, complementing the action of sage extract.

Phosphatidylserine

Phosphatidylserine is a phospholipid, one of the structural components of the membranes that surrounds all cells in the body. This is particularly critical for nerve cells in the brain because it is their cell membrane that carries nerve impulses throughout the nervous system.23 The myelin that surrounds nerve fibers and aids signal conduction also relies on phosphatidylserine for normal structure and function.

Aging is associated with structural deterioration in the nervous system, which may be reduced by phosphatidylserine, preserving cognitive function.

Phosphatidylserine is particularly notable as a brain health supplement in that it is the only supplement that has been given "qualified health claim" status for its potential to reduce the risk of cognitive decline and dementia in the elderly by the U.S. Food and Drug Administration. 24

Blueberry

Blueberries are packed full of anthocyanins, powerful oxidant-reducing compounds that help protect the plant from oxidative stress. These compounds have been explored in the medical literature for years for their potential health benefits to humans.

Several recent trials in humans have demonstrated that enhancement of cognitive function can be added to the list of blueberry's benefits. Not only has blueberry been found to enhance memory and other cognitive performance in older subjects, it improves mood and cognition in children and young adults as well.25-29

Vinpocetine

Vinpocetine is a compound derived from the periwinkle plant.

It has been reported to have benefits for cognition and degenerative disorders of the brain such as Alzheimer's and Parkinson's disease due to multiple nervous system effects.30 It acts as a dilator of blood vessels to the brain, improving blood flow, as well as stimulating brain metabolism.

Pregnenolone

Pregnenolone is a hormone and hormone-precursor. It and its derivatives formed in the brain have modulatory effects on nervous system function.

Several studies in animals and humans have reported beneficial effects for the brain.31 It appears to be a neuroprotectant, defending the brain from various forms of injury. It has also been found to have positive effects on mood, memory, and other aspects of cognition.

Ashwagandha

Ashwagandha is an Indian herb also referred to as "Indian Ginseng". It has been used in traditional Indian medicine as a nerve tonic for millennia.

In modern research, ashwagandha has demonstrated neuroprotective effects and improvements in mood and cognition.32,33

For example, a recent study in patients suffering from mild cognitive impairment found that ashwagandha led to improvements in memory and other markers of cognitive functioning such as attention and decision-making executive function.32

Uridine 5'-monophosphate

Uridine 5'-monophosphate is a nucleic acid, a precursor necessary for the synthesis of RNA and proteins. In addition, it contributes to the production of components of synapses, the region where brain cells communicate with each other.34

Loss of functional synapses contributes to the decline in brain function with age and various degenerative diseases. Therefore, by aiding nerve cell functions related to synapses uridine is believed to help preserve brain function and protect it from degeneration.34

Readers of this magazine have been using some or all these nutrients for many decades to protect and enhance cognitive functionality.

Initial Human Studies

Sage extracts were tested in a series of trials in younger people.8,9,15,16

In each of these trials, scientists found that sage induced beneficial effects on mood and cognition.

Within hours of consuming the sage supplements, these younger subjects benefited from improved mood, reduced anxiety, enhanced long-term memory/attention, and reduced mental fatigue.

Sage extracts have also been studied in older individuals with Alzheimer's disease.11,17 In a preliminary study of Alzheimer's patients, sage extract improved neuropsychiatric symptoms and attention.11

In a randomized clinical trial of patients with mild-to-moderate Alzheimer's dementia, one arm of the study received a sage extract and the other a placebo.17 The researchers used a scoring system designed to evaluate cognitive functions in Alzheimer's patients.

Results of this study showed that over the course of four months, cognitive scores of people who received placebo deteriorated by about 22%. The study subjects supplemented with sage extract improved by about 26%.

Considering that these people presented with clinical indicators of mild-to-moderate dementia, the improvement seen after four months in the sage supplemented group is quite remarkable.

Mild Cognitive Impairment & Alzheimer's Disease

One of the most prevalent health concerns for the brain is age-related cognitive decline.

Early deterioration in brain function beyond that expected for one's age is referred to as mild cognitive impairment, affecting memory, attention, and other mental processes. Dementia refers to more severe loss of cognitive function. The most common cause of dementia by far is Alzheimer's disease. These two diagnoses are characterized by lower levels of acetylcholine.

Both of these disorders are very common, affecting millions of adults in the U.S. alone.

New Standardized Sage Extract

Findings from the human studies described thus far led to a search for compounds in sage responsible for these improvements in cognitive function.

An intensive investigation using advanced analytic techniques identified a sage plant that has superior biological activity.2

The result of this research is a standardized sage extract that has demonstrated improved mechanistic properties in microarray gene expression studies.3

To test this new sage extract in the real world, a rigorous study of cognition in aging humans was conducted.

Enhancement of Cognition in Aging Humans

Foods considered as a part of the Mediteranian diet

Using this standardized sage extract, a clinical study evaluated the effect on cognition in adults over age 64.1

The subjects underwent a battery of brain function tests before and after receiving this novel sage extract or placebo.

Here are the results:

  • Compared with placebo, memory performance in people receiving the sage extract was boosted by roughly 60%.
  • Compared to placebo, measures of attention were enhanced approximately 2.5-fold in sage-supplemented subjects.
  • These effects occurred rapidly, improving brain function within hours of intake of this new sage extract.

Cognitive function tends to decrease over the course of a day, resulting in worsening memory performance and accuracy of attention. Supplementation with sage extract enhanced both of these aspects of brain function in these subjects.

Potential Lifespan Increase

Pathologic aging is partially characterized by disruption of genes involved in insulin signaling and lipid metabolism.

These effects are revealed in blood tests showing increases in glucose, cholesterol, and triglycerides as people grow older.

In a laboratory model of aging, this new sage extract was studied on the C. elegans roundworm. This kind of testing is used to identify the impact of compounds on human longevity potential.2

This particular sage extract was found to increase expression of lipid metabolism and insulin signaling genes, which have been tied to enhanced longevity.3

The result was a 12% lifespan increase in C. elegans that were fed this novel sage extract. Other sources of sage tested did not demonstrate extended life.2

Improved Neurotransmitter Signaling

As it relates to short-term memory loss, acetylcholine is one of the most studied neurotransmitters in the aging brain. By inhibiting the enzyme that degrades acetylcholine, extracts from sage have consistently been shown to improve cognitive performance.

In addition to acetylcholine, several other neurotransmitters are adversely affected by aging.

This novel sage extract has been shown to favorably modulate gene expression of other neurotransmitters crucial for cognitive function, such as GABA and glutamate.3

These findings explain the profound benefits observed in human studies that extend beyond boosting acetylcholine brain levels.

Improved Blood Flow to the Brain

Aging is associated with a reduction of blood flow to the brain, which contributes to adverse changes in cognitive function.20

A significant body of evidence points to diminished cerebral circulation as a precursor to both vascular and Alzheimer's dementia.

As we reported in the March 2014 issue of this magazine, loss of blood flow to the brain is a greater problem than most people realize. Here is one quote from what we published:21

"According to a study conducted at the Mayo Clinic, a surprising number of aging people
suffer a condition in which tiny areas of their brain become oxygen deprived. This cerebral
vascular deficit sharply increases risk of stroke, dementia, and cognitive impairment.
Healthy lifestyle choices can prevent and may help reverse it."22

This new sage extract may guard against this circulatory reduction as it has been found to have vasodilator properties, opening blood vessels that supply the brain.3

Summary

Foods considered as a part of the Mediteranian diet

The herb sage is uniquely suited to protecting brain function from deterioration associated with aging and dementia by several complementary mechanisms.

It also augments current cognitive function by enhancing levels of the neurotransmitter acetylcholine in the brain.

Scientists in England identified a proprietary standardized sage extract that protects and enhances cognitive function.

This extract has been found to have a unique chemical makeup18 and additional biological effects not previously identified in other sage preparations.2

This new sage extract has uniquely demonstrated the ability to extend lifespan in laboratory models and to improve cognition in elderly human subjects.

Coupled with other nutrients such as phosphatidylserine, blueberry, vinpocetine, and others, sage can be an important component of a comprehensive formula for the brain.

If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.

References

  1. Scholey AB, Tildesley NT, Ballard CG, et al. An extract of Salvia (sage) with anticholinesterase properties improves memory and attention in healthy older volunteers. Psychopharmacology (Berl). 2008May;198(1):127-39.
  2. Sibelius. Internal Report. ChronoscreenTM Analysis: Cognition Enhancing Drugs & Natural Extracts. 2018.
  3. Confidential S. Sage Gene Expression Analysis. 2018.
  4. Francis PT. The interplay of neurotransmitters in Alzheimer’s disease. CNS Spectr. 2005Nov;10(11 Suppl 18):6-9.
  5. Klinkenberg I, Sambeth A, Blokland A. Acetylcholine and attention. Behav Brain Res. 2011Aug 10;221(2):430-42.
  6. Garcia-Ayllon MS, Small DH, Avila J, et al. Revisiting the Role of Acetylcholinesterase in Alzheimer’s Disease: Cross-Talk with P-tau and beta-Amyloid. Front Mol Neurosci. 2011;4:22.
  7. Mueller C, Perera G, Hayes RD, et al. Associations of acetylcholinesterase inhibitor treatment with reduced mortality in Alzheimer’s disease: a retrospective survival analysis. Age Ageing. 2018Jan 1;47(1):88-94.
  8. Kennedy DO, Dodd FL, Robertson BC, et al. Monoterpenoid extract of sage (Salvia lavandulaefolia) with cholinesterase inhibiting properties improves cognitive performance and mood in healthy adults. J Psychopharmacol. 2011Aug;25(8):1088-100.
  9. Kennedy DO, Pace S, Haskell C, et al. Effects of cholinesterase inhibiting sage (Salvia officinalis) on mood, anxiety and performance on a psychological stressor battery. Neuropsychopharmacology. 2006Apr;31(4):845-52.
  10. Lopresti AL. Salvia (Sage): A Review of its Potential Cognitive-Enhancing and Protective Effects. Drugs R D. 2017Mar;17(1):
    53-64.
  11. Perry NS, Bollen C, Perry EK, et al. Salvia for dementia therapy: review of pharmacological activity and pilot tolerability clinical trial. Pharmacol Biochem Behav. 2003Jun;75(3):651-9.
  12. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677-736.
  13. Erickson KI, Prakash RS, Voss MW, et al. Brain-derived neurotrophic factor is associated with age-related decline in hippocampal volume. J Neurosci. 2010Apr 14;30(15):5368-75.
  14. Hasanein P, Felehgari Z, Emamjomeh A. Preventive effects of Salvia officinalis L. against learning and memory deficit induced by diabetes in rats: Possible hypoglycaemic and antioxidant mechanisms. Neurosci Lett. 2016May 27;622:72-7.
  15. Tildesley NT, Kennedy DO, Perry EK, et al. Salvia lavandulaefolia (Spanish sage) enhances memory in healthy young volunteers. Pharmacol Biochem Behav. 2003Jun;75(3):669-74.
  16. Tildesley NT, Kennedy DO, Perry EK, et al. Positive modulation of mood and cognitive performance following administration of acute doses of Salvia lavandulaefolia essential oil to healthy young volunteers. Physiol Behav. 2005Jan 17;83(5):699-709.
  17. Akhondzadeh S, Noroozian M, Mohammadi M, et al. Salvia officinalis extract in the treatment of patients with mild to moderate Alzheimer’s disease: a double blind, randomized and placebo-controlled trial. J Clin Pharm Ther. 2003Feb;28(1):53-9.
  18. Sibelius cognition enhancement product presentation. 2018.
  19. Available at: https://www.nutraceuticalsnow.com/articles/2018/03/05/interrogating-molecular-responses-nutraceuticals-gain-insights-health-benefits/. Accessed September 14, 2018.
  20. Chen JJ, Rosas HD, Salat DH. Age-associated reductions in cerebral blood flow are independent from regional atrophy. Neuroimage. 2011Mar 15;55(2):468-78.
  21. Available at: https://www.lifeextension.com/Magazine/2014/3/Leukoaraiosis-A-Hidden-Cause-Of-Brain-Aging/Page-01. Accessed November 1, 2018.
  22. Available at: https://www.medicalnewstoday.com/articles/249005.php. Accessed November 1, 2018.
  23. Glade MJ, Smith K. Phosphatidylserine and the human brain. Nutrition. 2015Jun;31(6):781-6.
  24. Taylor CL. Qualified health claim: final decision letter - phosphatidylserine and cognitive dysfunction and dementia. U.S. Food & Drug Administration;2003.
  25. Whyte AR, Cheng N, Fromentin E, et al. A Randomized, Double-Blinded, Placebo-Controlled Study to Compare the Safety and Efficacy of Low Dose Enhanced Wild Blueberry Powder and Wild Blueberry Extract (ThinkBlue) in Maintenance of Episodic and Working Memory in Older Adults. Nutrients. 2018May 23;10(6).
  26. McNamara RK, Kalt W, Shidler MD, et al. Cognitive response to fish oil, blueberry, and combined supplementation in older adults with subjective cognitive impairment. Neurobiol Aging. 2018Apr;64:147-56.
  27. Whyte AR, Schafer G, Williams CM. Cognitive effects following acute wild blueberry supplementation in 7- to 10-year-old children. Eur J Nutr. 2016Sep;55(6):2151-62.
  28. Miller MG, Hamilton DA, Joseph JA, et al. Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial. Eur J Nutr. 2018Apr;57(3):1169-80.
  29. Khalid S, Barfoot KL, May G, et al. Effects of Acute Blueberry Flavonoids on Mood in Children and Young Adults. Nutrients. 2017Feb 20;9(2).
  30. Zhang YS, Li JD, Yan C. An update on vinpocetine: New discoveries and clinical implications. Eur J Pharmacol. 2018Jan 15;819:30-4.
  31. Vallee M. Neurosteroids and potential therapeutics: Focus on pregnenolone. J Steroid Biochem Mol Biol. 2016Jun;160:78-87.
  32. Choudhary D, Bhattacharyya S, Bose S. Efficacy and Safety of Ashwagandha (Withania somnifera (L.) Dunal) Root Extract in Improving Memory and Cognitive Functions. J Diet Suppl. 2017Nov 2;14(6):599-612.
  33. Singh N, Bhalla M, de Jager P, et al. An overview on ashwagandha: a Rasayana (rejuvenator) of Ayurveda. Afr J Tradit Complement Altern Med. 2011;8(5 Suppl):208-13.
  34. Wurtman RJ. Synapse formation in the brain can be enhanced by co-administering three specific nutrients. Eur J Pharmacol. 2017Dec 15;817:20-1.

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