Lithium orotate (low-dose)

What it is

Lithium has two completely different faces. One is the medicine: lithium carbonate is approved as a prescription drug and has been used in psychiatry for decades, for example for bipolar disorder, with close medical monitoring. The other is the trace element: lithium is present in traces in water and food, and every person carries it, including in the brain.

Lithium orotate is a salt in which lithium is bound to orotic acid. In the biohacking world it is taken in microdoses, that is, in amounts far below the psychiatric dose. Officially, lithium is currently considered a non-essential trace element, and the German Nutrition Society has not set a reference value. Proponents such as the physician Michael Nehls, by contrast, consider lithium an underestimated, vital nutrient whose deficiency is said to be widespread.

The 2025 Nature study

The research group led by Bruce Yankner at Harvard Medical School used mass spectrometry to measure 27 metals in the brain and blood of older people with healthy memory, with mild cognitive impairment and with Alzheimer’s. Only one metal was significantly reduced in the brain in mild cognitive impairment, the precursor stage of Alzheimer’s: lithium. In Alzheimer’s it was additionally bound in the amyloid deposits. The plaques thus act like a sponge that soaks up free lithium.

In the mouse experiment, the researchers lowered the body’s own lithium in the cerebral cortex by about 50 percent via the diet. That was enough to trigger more amyloid deposits, more aggregated tau, inflammatory activated immune cells, the loss of synapses and nerve fibers and faster cognitive decline. This was mediated at least in part via the enzyme GSK3β. Then the real twist: lithium orotate is barely captured by amyloid. At a low dose it prevented the pathological changes and memory loss in Alzheimer’s mouse models and in normally aging mice.

How it is supposed to work

Lithium inhibits the enzyme GSK-3, which is involved in the aggregation of tau, and is said to promote growth factors for nerve cells such as BDNF, stimulate cellular waste disposal and dampen inflammation. That is why it is referred to as a neuroprotective agent, a nerve-protecting substance. For the mouse findings of the Nature study, mediation via GSK3β has been shown directly.

The second strand is mood. That lithium stabilizes mood at a therapeutic dose is undisputed. The question is whether traces already have an effect. In user circles, less irritability and less rumination are consistently reported, often within a few days. These are anecdotal reports; it has not been tested.

Lithium in drinking water

How much lithium is naturally present in tap water varies greatly from region to region. This gave researchers the idea of comparing places of residence. In 18 municipalities of the Japanese prefecture of Oita, more lithium in the water went along with fewer suicides. A meta-analysis of 15 such ecological studies found an overall protective association with suicide mortality.

For dementia there is a large Danish study with 73,731 patients and 733,653 controls. Those who drank water with more than 15.0 micrograms of lithium per liter over the long term had a lower dementia risk compared with 2.0 to 5.0 micrograms, with an incidence rate ratio of 0.83. These signals are the reason why lithium is being discussed as a trace element for the brain.

What the studies show

Aron et al., Nature 2025 — lithium deficiency and Alzheimer’s

Analysis of 27 metals in brain tissue and blood of older people: only lithium was reduced in the brain in mild cognitive impairment, and in Alzheimer’s it was additionally bound in amyloid. In the mouse experiment, lowering cortical lithium by about 50 percent led to amyloid, tau aggregation, inflammation, synapse loss and faster cognitive decline. Lithium orotate prevented these changes and the memory loss without altering kidney values or TSH. No humans received lithium in this study.

Kessing et al., JAMA Psychiatry 2017 — drinking water and dementia

Nationwide Danish case-control study with 73,731 dementia patients between 50 and 90 years of age and 733,653 controls. The association was not linear: above 15.0 micrograms per liter the dementia rate was lower, with a rate ratio of 0.83; between 10.1 and 15.0 micrograms it was unchanged, at 0.98; and between 5.1 and 10.0 micrograms it was even higher, at 1.22. The authors cannot rule out other factors of the place of residence.

Memon et al., British Journal of Psychiatry 2020 — drinking water and suicide

Systematic review with meta-analysis: from 415 screened articles, 15 ecological studies were pooled. More lithium in drinking water went along with lower overall suicide mortality, though with high variation between studies. The authors stress that such comparisons at the population level are prone to false conclusions and propose randomized community trials.

Where the data stop

The decisive step is still missing: a controlled study in which people receive lithium orotate in microdoses and are examined for memory, dementia risk or mood. The Nature findings on the orotate come from mice, and the study describes that it prevented damage. The German consumer advice center (Verbraucherzentrale) therefore describes a dementia-protective effect as scientifically unproven.

The drinking water data are also less consistent than they are often portrayed. The largest study with individual-level data, 3.7 million adults in Denmark over 22 years, found no association between lithium in water and suicides, and neither did a study in 47 areas in the east of England. In the Danish dementia study, the middle range of 5.1 to 10.0 micrograms per liter was even associated with more dementia. And drinking water supplies lithium in microgram amounts over decades; whether a capsule does the same has not been tested by anyone.

Status, approval and legal

In Germany and the EU, lithium is not authorized as a dietary supplement and may not be sold as one: Annex II of the Food Supplements Directive 2002/46/EC contains no lithium compound. Only lithium carbonate is approved, as a prescription medicine. The consumer advice centers advise against taking it on your own. For this reason, we do not state a dosage.

Safety

The known side effects of lithium belong to the high-dose world: with long-term therapy, the kidneys, thyroid and parathyroid glands can be damaged, and an overdose can lead to poisoning with impairment of the brain and kidneys. For low-dose lithium orotate there are animal data without signs of kidney or thyroid toxicity, but no systematic safety data in humans. You should seek medical advice beforehand in case of kidney disease, thyroid problems, diuretics, pregnancy and breastfeeding and if you take medications for the nervous system. Microdose lithium is not a substitute for treatment when someone is seriously mentally ill.

Sources

• Aron et al., Nature 2025
• Kessing et al., JAMA Psychiatry 2017
• Memon et al., British Journal of Psychiatry 2020
• Ohgami et al., British Journal of Psychiatry 2009
• Knudsen et al., International Journal of Environmental Research and Public Health 2017
• Kabacs et al., British Journal of Psychiatry 2011
• Verbraucherzentrale (German consumer advice center): lithium orotate