Restore Youthful Cognitive FunctionJanuary 2019
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.
Sage Extracts Protect the Brain
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
Growing New Brain Cells
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.
Oxidative Stress and Inflammation
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
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.
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
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
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.
- 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.
- Sibelius. Internal Report. ChronoscreenTM Analysis: Cognition Enhancing Drugs & Natural Extracts. 2018.
- Confidential S. Sage Gene Expression Analysis. 2018.
- Francis PT. The interplay of neurotransmitters in Alzheimer’s disease. CNS Spectr. 2005Nov;10(11 Suppl 18):6-9.
- Klinkenberg I, Sambeth A, Blokland A. Acetylcholine and attention. Behav Brain Res. 2011Aug 10;221(2):430-42.
- 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.
- 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.
- 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.
- 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.
- Lopresti AL. Salvia (Sage): A Review of its Potential Cognitive-Enhancing and Protective Effects. Drugs R D. 2017Mar;17(1):
- 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.
- Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677-736.
- 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.
- 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.
- 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.
- 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.
- 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.
- Sibelius cognition enhancement product presentation. 2018.
- Available at: https://www.nutraceuticalsnow.com/articles/2018/03/05/interrogating-molecular-responses-nutraceuticals-gain-insights-health-benefits/. Accessed September 14, 2018.
- 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.
- Available at: https://www.lifeextension.com/Magazine/2014/3/Leukoaraiosis-A-Hidden-Cause-Of-Brain-Aging/Page-01. Accessed November 1, 2018.
- Available at: https://www.medicalnewstoday.com/articles/249005.php. Accessed November 1, 2018.
- Glade MJ, Smith K. Phosphatidylserine and the human brain. Nutrition. 2015Jun;31(6):781-6.
- Taylor CL. Qualified health claim: final decision letter - phosphatidylserine and cognitive dysfunction and dementia. U.S. Food & Drug Administration;2003.
- 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).
- 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.
- 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.
- 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.
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- Vallee M. Neurosteroids and potential therapeutics: Focus on pregnenolone. J Steroid Biochem Mol Biol. 2016Jun;160:78-87.
- 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.
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