Life Extension Magazine®
For decades, research has suggested that lithium has unique health benefits.
It may help prevent cognitive decline1,2 and may slow the aging process.3-5
Much of lithium’s impact is due to its inhibition of an enzyme in the body known as glycogen synthase kinase-3 (GSK-3).
GSK-3 overactivity has been tied to rapid aging and risk for chronic diseases.
Studies suggest that GSK-3 inhibition is largely responsible for lithium’s ability to protect brain function and extend lifespan.3
Lithium may inhibit cellular senescence, an effect that has been shown to increase longevity in preclinical studies.6-8
Even at low doses, lithium intake has been associated with decreased all-cause mortality in humans and increased longevity in roundworms.9
Two studies have found that individuals living in areas with even modest, low levels of lithium in the drinking water tend to live longer.9,10
Small, daily lithium doses (around 1,000 mcg) may be an effective way to slow aging and cognitive decline.
Brief History of Lithium
The element lithium is believed to have been created just minutes after the Big Bang, even before the stars and galaxies began to form.11
On Earth, it’s found in nearly all rocks. As water flows over and through rock formations and subsoil, it picks up small amounts of lithium.
For thousands of years, when people drank from natural bodies of water, they took in tiny doses of lithium.
Over time, water that had the highest-lithium concentrations became recognized for its health promoting properties. People even traveled hundreds of miles, making pilgrimages to lithium-rich springs.
For instance, Lithia Springs in Georgia, an area of naturally abundant lithium in the water, became a draw for people from all over the country. Prominent figures, from Mark Twain to at least four U.S. presidents, made trips to the springs specifically to drink the water.
In the last century, high doses of lithium—thousands of times higher than those in water—were found to be an effective treatment for bipolar disorder and depression.
And in recent years, scientists have made discoveries that help explain lithium’s wide-ranging benefits.
Slowing Aging
One of the most important ways lithium benefits the body is by inhibiting the activity of a powerful regulatory enzyme called glycogen synthase kinase-3 (GSK-3).3-5
GSK-3 controls several important functions in cells.
But overactivity of GSK-3, which occurs frequently with age, may be harmful.
Too much GSK-3 activity could rob cells of the ability to defend themselves against many of the ravages of time.4,12-17
In fact, increased GSK-3 activity correlates with more rapid aging of many tissues and the body as a whole.15,17 The impact is so great, GSK-3 can be thought of as an age-accelerating enzyme.
Excess GSK-3 activity may also raise the risk for chronic disorders of older age, including type II diabetes, Alzheimer’s, mood disorders, cancer, and others.4,12-14,16
The link between GSK-3 and aging and disease is so strong that since the 1970s researchers have been developing medications to reduce GSK-3 activity.
These scientists believe that a compound that reduces GSK-3 activity may be effective against age-related disorders such as type II diabetes.
Since lithium reduces GSK-3 overactivity at low doses, numerous age-related health problems could potentially safely be reduced without resorting to high-potency lithium drugs.3-5
Studies suggest that GSK-3 inhibition is largely responsible for lithium’s ability to protect brain function.3
Lithium May Extend Longevity
In addition to the well-known positive effects on mood,18 lithium has also been linked with longer overall longevity.
Two studies have found that individuals living in areas with even modest, low levels of lithium in the drinking water tend to live longer.9,10
This pattern has also been observed in people taking high-dose lithium for medical reasons. They generally have lower mortality rates, including lower rates of death due to cardiovascular disease.19,20
Studies in animals have supported these findings and have helped identify the potential biological mechanisms by which lithium extends longevity.
For example, studies in fruit flies and the roundworm C. elegans show that high doses of lithium supplementation lead to longer lifespan.3,6,9 The median survival of the animals in one of these studies was increased by as much as 46%.6
These effects were seen at very high doses, but even at low doses, lithium has been shown to modestly increase lifespan in C. elegans.9
Scientists believe lithium may promote longevity by protecting cellular genetic material from age-related deterioration. It may do this in three main ways:6-8
- Lithium may help maintain longer telomeres, structures associated with DNA health and longer life, as seen in long-term, high-dose treatment.
- Lithium regulates genes related to healthy DNA structure.
- Lithium may offer protection from cellular senescence, when elderly cells cease functioning properly but won’t die off. These senescent cells are major contributors to age-related ailments and faster aging.
These mechanisms pack a powerful punch against premature aging and degenerative illnesses.
What you need to know
The Wide-Ranging Benefits of Lithium
- Lithium is a trace mineral found in the earth’s crust, and therefore in some, but not all, drinking water.
- Studies suggest that GSK-3 inhibition is also largely responsible for lithium’s ability to protect brain function and extend lifespan.
- Even at low doses, lithium intake has been associated with decreased all-cause mortality in humans and increased longevity in roundworms.
- Lithium plays a critical role, from slowing the aging process to protecting the brain and improving mental health, and more.
- Small daily doses of lithium may be an effective way to slow aging and cognitive decline and extend life.
Lithium and the Brain
In 2018, researchers studying lithium levels in different counties in Texas discovered that rates of death from Alzheimer’s disease were higher in areas with low levels of lithium in the water.10
This came on the heels of a Danish study that found that higher long-term lithium intake from drinking water may be associated with a lower risk of being diagnosed with dementia.21
Clinical studies of lithium in the treatment of dementia show similarly encouraging results.
In one study, a micro-dose of just 300 mcg of lithium daily significantly decreased cognitive decline in Alzheimer’s patients compared to a placebo.22
A recent review found that cognitive function of individuals with early-stage dementia remained more stable in those given lithium than in those who took a placebo.23
In addition to reducing the elevated GSK-3 activity associated with Alzheimer’s, one preclinical study showed that lithium reduces the build-up of beta-amyloid, the abnormal protein that accumulates and forms plaques in the brains of Alzheimer’s patients.24
Other Biological Effects
Research has revealed many other biological effects in those using long-term, high-dose lithium treatment for medical conditions.5
- It reduces cell death and improves cellular resilience and plasticity.
- It increases the activity of multiple beneficial neurotransmitters in the brain.
- It has balancing effects on the circadian rhythm and hormonal function.
- It increases brain-derived neurotrophic factor, an important signaling molecule in the brain that protects brain cells and augments their function.
Scientists continue to discover new benefits of lithium all the time.
Summary
Lithium, an often-overlooked trace mineral, may help slow the aging process, extend lifespan, reduce risk for chronic diseases, and slow the worsening of cognitive decline.
Research shows that low doses of lithium ranging from 300 mcg to around 1,000 mcg daily may have a beneficial impact on mental and physical health and possibly 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.
References
- 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 Apr 5:1-7.
- 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.
- 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).
- 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.
- 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.
- 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.
- 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.
- Available at: https://physicsworld.com/a/big-bang-ruled-out-as-origin-of-lithium-6/. Accessed April 9, 2020.
- Henriksen EJ, Dokken BB. Role of glycogen synthase kinase-3 in insulin resistance and type 2 diabetes. Curr Drug Targets. 2006 Nov;7(11):1435-41.
- 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.
- Lei P, Ayton S, Bush AI, et al. GSK-3 in Neurodegenerative Diseases. Int J Alzheimers Dis. 2011;2011:189246.
- 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.
- Zhou J, Force T. Focusing the spotlight on GSK-3 in aging. Aging (Albany NY). 2013 Jun;5(6):388-9.
- Available at: https://www.nytimes.com/2014/09/14/opinion/sunday/should-we-all-take-a-bit-of-lithium.html. Accessed April 16, 2020.
- 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.
- 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.
- 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.
- Wittenberg SM, Toxopeus KA, Schulte PFJ. [Lithium and its protective effect in Alzheimer’s disease]. Tijdschr Psychiatr. 2017;59(9):559-63.
- 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.