By Michael Downey.
During the past two centuries, people made pilgrimages to springs that were naturally high in the mineral lithium.
One site, Lithia Springs in Georgia, was visited by Mark Twain, at least four U.S. presidents, and other prominent figures, all because of the famous lithium water.
The more that scientists study lithium, the more persuasive the evidence has become for its unique effects.
Scientists have found that lithium may prevent cognitive decline.1,2 Preclinical studies have shown it activates pathways that may slow the aging process.3,4
In one animal study, high doses of lithium increased median lifespan by 46%.5
Two studies have found that individuals living in areas with even modest levels of lithium in drinking water tend to live longer.6,7
As little as 300 to 1,000 mcg of lithium daily may provide these benefits.
What is Lithium?
Lithium is a naturally occurring mineral found in rocks and subsoil in some geographical areas. Some natural water sources contain small amounts of this element.
By the 19th century, many people had come to believe that there were health and longevity benefits to drinking water that contained lithium. It also became linked to improved mood.
Modern science has confirmed these beliefs.
For instance, two studies found that people living in areas with even low levels of lithium in the drinking water tend to live longer.6,7
Lithium and the ‘Age-Accelerating Enzyme’
One key to lithium’s benefits appears to be its ability to inhibit a cellular enzyme called glycogen synthase kinase-3 (GSK-3).3,4,8
GSK-3 controls several important functions within cells. But overactivity of GSK-3 can be harmful.
Increased GSK-3 activity correlates with rapid aging of many tissues and the entire body.9,10 Its impact is so dramatic that GSK-3 can be thought of as an age-accelerating enzyme.
Overactivity of GSK-3 is linked to chronic diseases, including Alzheimer’s, type II diabetes, some cancers, and mood disorders.4,11-14
Even in low doses, lithium reduces GSK-3 overactivity.3,4,8
Studies suggest that this GSK-3 inhibition is largely responsible for lithium’s ability to protect brain function and promote healthy longevity.3,8
Scientists have noted that people taking high-dose lithium for medical reasons generally have lower mortality rates, including lower rates of death due to cardiovascular disease.15,16
Controlled experiments have been conducted to rigorously explore possible life-extending effects of lithium.
These studies showed that low-dose lithium led to a modest increase in lifespan in roundworms, known as C. elegans.7
Higher doses of lithium led to longer lifespans in both roundworms and fruit flies.3,5,7 In one of these studies, median survival was boosted by 46%.9
Evidence from these and other studies suggested that, in addition to inhibiting GSK-3, lithium exerted pro-longevity effects in three ways:5,17,18
- Lithium may help maintain longer telomeres, protective structures related to cellular health,
- Lithium regulates genes related to healthy DNA structure, and
- Lithium may protect against cell senescence. Senescent cells are contributors to age-related disease and accelerated aging.
Together, these mechanisms may help slow the aging process and protect against chronic disease.
Protecting the Brain
Very high doses of lithium have long been used to treat the psychiatric condition bipolar disorder.
Now, clinical studies suggest that much lower doses of lithium provide neuroprotective benefits.
Scientists are finding that lithium may help prevent or improve mood disorders, dementia, and Alzheimer’s disease.
One study found that long-term lithium exposure from drinking water may be associated with a lower risk of being diagnosed with dementia.19
Similar benefits have been demonstrated with Alzheimer’s disease.
One epidemiological study in Texas revealed that rates of death from Alzheimer’s were higher in areas with low levels of lithium in the water.20
In one clinical study, a micro-dose of just 300 mcg of lithium daily was found to significantly decrease cognitive decline in Alzheimer’s patients, compared to a placebo.21
Mechanisms of Neuroprotection
Lithium appears to protect the brain in a number of different ways.
In preclinical research, scientists found that it not only reduces the elevated GSK-3 activity associated with Alzheimer’s, but also reduces the buildup of beta-amyloid. This is the abnormal protein that accumulates and forms plaques in the brains of Alzheimer’s patients.22
Scientists have also documented that lithium:8
- Increases the activity of multiple beneficial neurotransmitters in the brain,
- Increases brain-derived neurotrophic factor, an important signaling molecule that protects brain cells and augments their function, and
- Helps balance circadian rhythm and may help with adrenal hormone function.
WHAT YOU NEED TO KNOW
Lithium’s Brain and Body Benefits
- Studies have found that people living in areas with the mineral lithium in the drinking water tend to live longer.
- Patients taking lithium for medical reasons also have lower mortality rates, and lithium treatment extends lifespan in animal studies.
- Lithium in drinking water may also be associated with a lower risk of being diagnosed with dementia.
- In a clinical study, 300 mcg of lithium daily significantly decreased cognitive decline in patients with Alzheimer’s disease.
- Lithium appears to work largely by inhibiting overactivity of the “age-accelerating enzyme” GSK-3, which has been tied to rapid aging, cognitive decline, and risk for chronic diseases.
- Low-dose lithium may reduce risk for age-related disorders, protect brain function, and extend healthy lifespan.
In clinical studies, lithium treatment has been linked to additional signs of neuroprotection, including:23
- Thickening of the cerebral cortex, the brain’s outer layer,
- Increased density of gray matter, which contains most of the brain’s nerve cell bodies, and
- Enlargement of the hippocampus, the brain’s memory center.
All of these activities together may slow brain aging and protect against cognitive decline.
The mineral lithium is demonstrating broad-spectrum health benefits.
Lithium works, in part, by inhibiting the overactivity of the “age-accelerating enzyme” GSK-3 and protecting DNA.
Lithium intake is associated with longer lifespan in humans and a median 46% increase in longevity in roundworms.
In a clinical study, it decreased cognitive decline in patients with Alzheimer’s disease.
Research shows that low lithium doses—only 300 mcg to about 1,000 mcg daily—may benefit mental and physical health and increase longevity.
If you have any questions on the scientific content of this article, please call a Life Extension® Wellness Specialist at 1-866-864-3027.
- Matsunaga S, Kishi T, Annas P, et al. Lithium as a Treatment for Alzheimer’s Disease: A Systematic Review and Meta-Analysis. J Alzheimers Dis. 2015;48(2):403-10.
- Forlenza OV, Radanovic M, Talib LL, et al. Clinical and biological effects of long-term lithium treatment in older adults with amnestic mild cognitive impairment: randomised clinical trial. Br J Psychiatry. 2019 Nov;215(5):668-74.
- Castillo-Quan JI, Li L, Kinghorn KJ, et al. Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis. Cell Rep. 2016 Apr 19;15(3):638-50.
- Saraswati AP, Ali Hussaini SM, Krishna NH, et al. Glycogen synthase kinase-3 and its inhibitors: Potential target for various therapeutic conditions. Eur J Med Chem. 2018 Jan 20;144:843-58.
- McColl G, Killilea DW, Hubbard AE, et al. Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans. J Biol Chem. 2008 Jan 4;283(1):350-7.
- Fajardo VA, LeBlanc PJ, Fajardo VA. Trace lithium in Texas tap water is negatively associated with all-cause mortality and premature death. Appl Physiol Nutr Metab. 2018 Apr;43(4):412-4.
- Zarse K, Terao T, Tian J, et al. Low-dose lithium uptake promotes longevity in humans and metazoans. Eur J Nutr. 2011 Aug;50(5):387-9.
- Won E, Kim YK. An Oldie but Goodie: Lithium in the Treatment of Bipolar Disorder through Neuroprotective and Neurotrophic Mechanisms. Int J Mol Sci. 2017 Dec 11;18(12).
- Lei P, Ayton S, Bush AI, et al. GSK-3 in Neurodegenerative Diseases. Int J Alzheimers Dis. 2011;2011:189246.
- Zhou J, Force T. Focusing the spotlight on GSK-3 in aging. Aging (Albany NY). 2013 Jun;5(6):388-9.
- Henriksen BS, Curtis ME, Fillmore N, et al. The effects of chronic AMPK activation on hepatic triglyceride accumulation and glycerol 3-phosphate acyltransferase activity with high fat feeding. Diabetol Metab Syndr. 2013;5:29.
- Hooper C, Killick R, Lovestone S. The GSK3 hypothesis of Alzheimer’s disease. J Neurochem. 2008 Mar;104(6):1433-9.
- Jope RS, Roh MS. Glycogen synthase kinase-3 (GSK3) in psychiatric diseases and therapeutic interventions. Curr Drug Targets. 2006 Nov;7(11):1421-34.
- Zhang Y, Huang NQ, Yan F, et al. Diabetes mellitus and Alzheimer’s disease: GSK-3beta as a potential link. Behav Brain Res. 2018 Feb 26;339:57-65.
- Ahrens B, Grof P, Moller HJ, et al. Extended survival of patients on long-term lithium treatment. Can J Psychiatry. 1995 Jun;40(5):241-6.
- Cipriani A, Pretty H, Hawton K, et al. Lithium in the prevention of suicidal behavior and all-cause mortality in patients with mood disorders: a systematic review of randomized trials. Am J Psychiatry. 2005 Oct;162(10):1805-19.
- Squassina A, Pisanu C, Congiu D, et al. Leukocyte telomere length positively correlates with duration of lithium treatment in bipolar disorder patients. Eur Neuropsychopharmacol. 2016 Jul;26(7):1241-7.
- Zmijewski JW, Jope RS. Nuclear accumulation of glycogen synthase kinase-3 during replicative senescence of human fibroblasts. Aging Cell. 2004 Oct;3(5):309-17.
- Kessing LV, Gerds TA, Knudsen NN, et al. Association of Lithium in Drinking Water With the Incidence of Dementia. JAMA Psychiatry. 2017 Oct 1;74(10):1005-10.
- Fajardo VA, Fajardo VA, LeBlanc PJ, et al. Examining the Relationship between Trace Lithium in Drinking Water and the Rising Rates of Age-Adjusted Alzheimer’s Disease Mortality in Texas. J Alzheimers Dis. 2018;61(1):425-34.
- Nunes MA, Viel TA, Buck HS. Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer’s disease. Curr Alzheimer Res. 2013 Jan;10(1):104-7.
- Sofola-Adesakin O, Castillo-Quan JI, Rallis C, et al. Lithium suppresses Abeta pathology by inhibiting translation in an adult Drosophila model of Alzheimer’s disease. Front Aging Neurosci. 2014;6:190.
- Forlenza OV, de Paula VJ, Machado-Vieira R, et al. Does lithium prevent Alzheimer’s disease? Drugs Aging. 2012 May 1;29(5):335-42.