What is lithium?

The word lithium is derived from the Ancient Greek word λίθος (líthos), meaning “stone”, for lithium is a minor component of most igneous rocks. As water passes through these, lithium makes its way into water and hence our drinking water and food. Lithium is also found in numerous salt basins, clay beds, and bedrock mines. Due to the uneven distribution of lithium in Earth’s crust, lithium intakes in some countries are low (barely 10 mcg in some European countries), whereas consumption in other places is much higher — over 50% of the world’s lithium reserves are concentrated in Argentina and Chile, so intakes are much higher there.

Some people have debated whether lithium is in fact an essential micronutrient, but it doesn’t seem to be indispensable for any one bodily process. It does, however, seem to be beneficial for a range of health outcomes, and is particularly beneficial for brain health and function when consumed in appropriate quantities.

Effects of lithium on lifespan and healthspan 

Studies of large groups of people that have estimated lithium intakes and monitored people’s health have highlighted lithium’s potential lifespan-extending properties. For example, among patients with mood disorders, those taking lithium had a 3.64 times lower chance of dying at a given age. Scientists have also tested whether lithium prolongs the lives of other animals. They’ve found that lithium extends the lifespans of several model organisms, including yeast, roundworms, and fruit flies. Lifespan studies of mice have not recapitulated this, although appropriate doses do slightly increase activity levels, reduce body fat, and improve blood sugar control in males. 

While studies of whether lithium prolongs the lives of mice haven’t been a home run, lithium does appear to affect several hallmarks of aging. Some of the positive effects of lithium on the brain described below seem to relate to the fact that lithium can increase autophagy in the brain, removing the kinds of dysfunctional proteins that associate with several neurodegenerative conditions. Lithium might also improve stem cell function, and counter chronic inflammation. There is also compelling evidence that lithium intake affects telomere length, in that bipolar patients treated with lithium have longer telomeres, and experiments on roundworms have shown that lithium affects the expression of a set of genes with a prominent effect on telomere length. Since some of the studies of these processes have focused on the brain and studies of adults have associated higher lithium intakes with reduced risk of developing several age-related brain pathologies, there is a compelling rationale that lithium is one of the most effective nutraceuticals at countering brain aging, specifically.

It makes sense to generally focus on lifespan and targeting the hallmarks of aging when developing gerotherapeutics. However, we believe that it’s possible to make products even better by addressing other factors that can prematurely cut short people’s lives. Lithium provides an interesting example of why narrowly focusing on preclinical lifespan experiments when reviewing candidate nutraceuticals to extend lifespan in humans is shortsighted. One of, if not the main reason we think lithium is advantageous in the context of human lifespan is that lithium intake is somewhat negatively associated with suicide. 

This is a big deal. 

Suicide accounts for over 800,000 deaths each year and is among the top 10 causes of age-standardised years of life lost in much of the world. Psychiatric issues dispose people to suicide, and time and time again it’s been found that patients with mood disorders such as bipolar who are on lithium therapy are less likely to take their own lives than their counterparts who don’t take lithium. Interestingly, evidence from the general population suggests that high doses of lithium might not be needed to protect against suicide though. In fact, lithium intake from drinking water has repeatedly been inversely associated with risk of suicide. As there is little evidence of other isolated dietary constituents being associated with risk of suicide, we were very keen to include lithium in Coastline.

Positive effects of lithium on human health

If you’ve heard of lithium in the context of health and disease, you’ve probably heard of its use as a mood-stabilising agent in bipolar disorder. And for good reason — lithium is the frontline therapy in treating the “manic” component of bipolar (in this context, mania is the dramatically increased energy, arousal, and mood that these people periodically experience). High doses of lithium (over 250 mg, producing serum lithium levels of at least 0.8 mmol/L) are typically used to treat bipolar. In contrast, many people are now interested in using lithium at much, much lower doses for other purposes. These include using lithium at trace doses (less than 5 mg), in keeping with what people in some parts of the world consume each day in drinking water. This is the use case that is most relevant to us, so we won’t go into the effects of lithium at the high doses used to manage psychiatric issues. 

Lithium might protect against the development of and progression of neurodegeneration

Some research suggests that lithium intake reduces risk of developing dementia, and there is preliminary evidence that trace doses of lithium can have impressive effects on several neurodegenerative conditions. Recent research on this subject has put lithium back in the spotlight. In this work, scientists looked at concentrations of metals in the brains of adults with either healthy brain function, mild cognitive impairment, or Alzheimer’s. Only one metal, lithium, differed in the prefrontal cortices (key to decision making, planning, reasoning, and social cognition) of healthy people and other groups, being higher in healthy people. One reason for this is that it seems that the amyloid plaques implicated in Alzheimer’s disease sequester lithium. This built on prior research on Alzheimer’s patients. In it, patients who consumed just 300 mcg lithium (as carbonate) each day for 15 months maintained their cognitive functions, as assessed by the Mini Mental State Exam. In contrast, patients in the control group deteriorated. This is remarkable, for Alzheimer’s disease has as yet proven notoriously difficult to treat. 

The researchers did many other experiments to decipher lithium’s actions, finding that dietary lithium deficiency accelerated brain accumulation of misfolded proteins and compromised learning and memory in mice genetically engineered to mimic familial Alzheimer’s disease. They also explored the effects of lithium deficiency on gene expression in several brain cell populations, finding a variety of changes thought to drive Alzheimer’s, such as degeneration of neurons, reduced myelination by oligodendrocytes (myelin speeds and reduces the cost of the transmission of signals through nerves), and increased oxidative stress by microglia, key cells in the brain’s immune surveillance system. Importantly, adding even very low levels of lithium orotate (lithium carbonate was not nearly as effective) to drinking water dramatically improved brain health and function, almost completely preventing the accumulation of misfolded proteins in the disease-prone mice and almost completely preventing memory loss. Similar benefits were evident in other, “wild-type” mice without this genetic disposition. 

Moving to another neurodegenerative disease, several lines of evidence point to the potential of low doses of lithium to reduce risk of and help treat Parkinson’s disease. A team of scientists led by Dr Thomas Guttuso is now exploring using low doses of lithium as a Parkinson’s treatment after a tiny pilot trial of a few patients documented preliminary but promising changes in a biomarker of disease severity (brain free water) after patients took lithium (as aspartate) at doses of 15 to 45 mg lithium. 

Lithium can lift and stabilise mood

Brain function affects mood, and various insults to the brain can worsen mood, including abuse of certain drugs. In a study of former drug abusers, people who took 400 mcg lithium for 4 weeks experienced positive effects on their mood relative to their peers who didn’t get supplemental lithium. Epidemiological studies have associated higher lithium intakes with lower rates of violent behavior too, although the evidence here is perhaps less compelling than it is for suicide. 

Precisely how lithium improves brain function is a matter of ongoing debate. It’s important to understand that most studies of these mechanisms involve exposure to high concentrations of lithium, which might not exactly map to the effects of trace doses of lithium. Nevertheless, we do know quite a lot about how lithium affects the body. 

Lithium enters cells throughout the body via sodium channels by simple diffusion, and some of lithium’s actions are by competing with sodium and magnesium ions, thereby inhibiting enzymes that depend on the sodium and magnesium. Perhaps the best accepted mechanisms involve this type of displacement and subsequent inhibition of the enzymes glycogen synthase kinase-3β and inositol monophosphatase. This inhibition, plus actions on other targets, sets in motion many downstream effects, including: regulation of the molecular clocks that influence daily rhythms of gene transcription in cells; increased transcription of genes that promote rewiring of the brain (neuroplasticity), such as BDNF; increased autophagy and associated improvements in proteostasis; and reduced inflammatory responses mounted by microglia.

Our use of lithium

Regarding dose, the amount of elemental lithium in Coastline (400 mcg) is consistent with 1) randomized controlled trials showing positive effects on cognitive function in Alzheimer’s disease and mood-boosting effects in adults with a history of substance abuse, and 2) tap water lithium levels associated with lower rates of suicide in population studies. To be clear, the dose is nowhere near the kinds of doses usually used to treat bipolar disorder — the doses used for many bipolar patients are over 100 times the dose in Coastline.

Regarding timing, when people take high doses of lithium to treat bipolar, most take lithium in the evening, for high doses often have some mild sedative effects. High doses of lithium can also change sleep architecture, promoting slow-wave sleep and reducing rapid eye movement sleep. (Incidentally, this shift in sleep structure can be especially beneficial in some disorders, such as depression.) By inhibiting the enzyme glycogen synthase kinase-3β, lithium is also a “chronobiotic”, meaning it directly affects the function of the circadian clocks that programme the daily timetable of events in your cells and hence your activity-rest rhythms each day. This effect on biological rhythms is one of the reasons high doses are so helpful in bipolar disorder. Lithium tends to shift the activity-rest rhythms of people who have bipolar earlier while also increasing the amplitude of these rhythms, both of which tend to be beneficial. At a trace dose like the one in Coastline, however, lithium is unlikely to have any substantial sedative or chronobiotic effects, so timing might be less important. Still, we’ve included it in the evening step of Coastline, in keeping with how high doses are taken.

Regarding form, lithium is available as many salts. Clinically, lithium carbonate is most commonly used, followed by lithium citrate, and carbonate is by far the best-studied form. However, these two salts are FDA-approved prescription drugs and so cannot be used in dietary supplements. Furthermore, despite having been more rigorously tested than its alternatives, it isn’t at all clear whether lithium carbonate is the pick of the bunch. It’s certainly bioavailable (80 to 100% of the lithium gets taken up in the upper intestine), but that doesn’t mean it cannot be improved upon. 

Of the other salts, the most popular forms in dietary supplements are lithium orotate and lithium aspartate. While there is much less research on these forms, both have been used in clinical trials, and there are reasons to think that both may more readily raise lithium levels in the serum and some cells than lithium carbonate. For example, in the aforementioned study of Parkinson’s patients, 45 mg lithium aspartate raised a marker of blood cell lithium levels more than 150 mg lithium carbonate did, although this shouldn’t be overinterpreted given there were so few patients. Regarding lithium orotate, this salt can increase brain lithium levels even at a dose of just 5 mg, and research on mice suggests it has several advantages over lithium carbonate, including higher therapeutic efficacy and reduced toxicity. In keeping with this, the latest research on Alzheimer’s disease biology flagged lithium orotate as being meaningfully more effective than lithium carbonate, perhaps because its lower ionization capacity than all other salts tested means it’s less likely to be taken up by amyloid. As a result, more of it is available to bolster the functions of brain cells. Whether this will translate to humans, time will tell.

In evaluating different forms of lithium, one consideration is whether the salt carrier has any effects independent of the lithium. At sufficient doses, the orotate in lithium orotate does affect human biology, in part because it’s used to make uridine, which is involved in synthesising DNA and RNA. Since in our case the lithium dose is only a trace dose though, the total mass of orotate is very unlikely to have any meaningful physiological effects. Indeed, there’s only about 10 mg of orotate in Coastline, roughly the amount in a small glass of cow’s milk, so we think in this case this point can be disregarded. (In contrast, if you use high doses of other mineral supplements bound to orotate, such as calcium and magnesium, you could be consuming over 10 g of orotate each day — 1,000 the amount in our product. We’re not sure taking such high doses is smart!)

In sum, we don’t think it’s currently clear whether lithium aspartate or orotate is superior, but if we had to bet, we’d put a small amount on orotate being better at delivering lithium to where we want it to go. 

Lithium typical dietary intakes and safety

How much lithium people consume each day varies substantially, largely due to geographical variation in drinking water lithium concentrations. Rarely, mineral waters have been found to contain as much as 20 mg lithium per litre, about 50 times the dose in Coastline. Others, however, contain none.

While at the high doses used to treat bipolar disorder, lithium does have some potential for adverse events and toxicity, even high doses are generally well tolerated. At trace doses like the one in Coastline, lithium is perfectly safe, and there are no reasons for concern whatsoever. The safety of such low amounts of lithium is made apparent by the lack of regulation of lithium levels in drinking water. Given lithium’s benefits, some scientists and other informed people are now proposing that drinking water lithium levels should be standardised, while others have pushed to fortify foods with trace doses of lithium, similar to the way iodine is added to salt in much of the world. One thing to remember is that not all lithium salts have equivalent potency, and since lithium orotate (the salt in Coastline) appears to be very effective at entering cells, the dose we use is very conservative, equal to the second lowest dose shown to be effective in clinical trials.