Lithium Orotate Reversed Brain Damage and Restored Memory in Mice

What is this is supposed to be? Not sure… Prompt: Lithium orotate

A deficiency of the metal lithium in the brain could be a key factor contributing to the development of dementia in Alzheimer’s patients, a groundbreaking study from Harvard Medical School reveals. The decade-long research, published in the journal Nature, is the first to show that lithium naturally occurs in the brain and is essential for maintaining the normal function of all major brain cell types, protecting nerves from degeneration.[1][2][3][4] Meta-analyses indicate that lithium therapy lowers the risk of Alzheimer’s disease and dementia overall, with risk reductions observed depending on treatment duration. The protective effects appear dose and duration dependent[14].

The scientists found that reduced lithium levels in the human brain were one of the earliest changes leading to Alzheimer’s disease. In mouse models, lithium depletion accelerated the buildup of hallmark Alzheimer’s pathology such as amyloid-beta plaques and tau tangles, worsened brain inflammation, and caused cognitive decline and memory loss. The deficiency disrupted key brain cell functions and impaired microglia — immune cells responsible for clearing toxic proteins — which exacerbates neurodegeneration. This lithium loss was partly due to impaired uptake and binding of lithium to amyloid plaques, which reduces its availability.[3][4][8][1]

Importantly, the researchers discovered that restoring lithium levels using a novel compound called lithium orotate (which evades capture by amyloid plaques) reversed brain damage and restored memory in mice. Maintaining stable lithium levels from early life also prevented Alzheimer’s onset in the mouse models. The study suggests lithium deficiency increases the activity of the enzyme glycogen synthase kinase 3 beta (GSK3β), which promotes neurodegenerative processes, while lithium treatment inhibits this harmful activity.[4][1][3]

There is no natural source of lithium orotate as such. Lithium orotate is a synthetic compound formed by combining lithium, a naturally occurring mineral, with orotic acid, a substance produced naturally in the body. Thus, lithium orotate does not occur naturally in foods or the environment. Orotic acid, the carrier molecule in lithium orotate, is produced by the human body, but the orotate salt with lithium is synthetic.

Dietary Lithium

From a nutritional perspective, lithium is found in trace amounts in various foods and drinking water, entering the human body primarily through diet. Natural lithium sources include:

– Leafy green vegetables
– Nuts
– Legumes
– Certain cereals, cabbages, and tomatoes
– Drinking water, especially from lithium-rich geological areas[7][9]

Major natural dietary sources of lithium include cereals, potatoes, tomatoes, cabbage, and some mineral waters. Lithium can also be found in certain spices like nutmeg, coriander, and cumin. Its concentration in foods varies depending on soil lithium levels and geography[12].

Lithium is found to some extent in tomatoes, mushrooms, thyme, pistachios, egg yolks, kelp, and sardines, depending on its presence in the soil or food source[23].

Lithium concentrations reported in mineral waters range from about 1 to over 1300 μg/L (1.3 mg/L), sometimes higher in special medicinal waters[13].

Though no official daily recommended intake for lithium exists, research, including a large Danish study linking higher long-term lithium exposure in drinking water to a reduced incidence of dementia, supports that low physiological levels of lithium might pose a health risk for cognitive decline.[5][9]

Lithium in Well Water by Region

Studies suggest even very low trace amounts of lithium in drinking water have been linked to lower dementia rates, supporting the idea that lithium at non-toxic doses might offer neuroprotective benefits[14].

Alzheimer’s dementia incidence is generally highest in the Eastern and Southeastern U.S., especially in states like Maryland, New York, Mississippi, and the Southern region overall. These areas show higher prevalence rates among older adults.

The U.S. Geological Survey (USGS) has produced lithium concentration maps by state, particularly showing lithium levels in groundwater and wells. A recent USGS study published in Environmental Science & Technology provides national estimates and mapping of naturally occurring lithium in U.S. groundwater used for drinking water, based on data from about 18,000 wells. This study found notable variations in lithium concentrations, especially elevated levels (30 micrograms per liter or higher) across western and southwestern states including Montana, Wyoming, North Dakota, South Dakota, Colorado, Utah, Nevada, Arizona, New Mexico, and Texas[16].

Additionally , there are 5 to 19 million tons of lithium in Smackover Formation brines in southern Arkansas. This amount would meet the 2030 world demand for lithium in car batteries nine times over[15].

Imperfect Correlation of Dementia and Low Lithium

Florida has a high rate of dementia and Alzheimer’s disease, partly due to having one of the largest aging populations in the U.S. Approximately 12.5% of Floridians aged 65 and older have Alzheimer’s disease—this corresponds to about 580,000 people living with Alzheimer’s in 2023, projected to reach 720,000 by 2025.[17] Regional studies confirm Florida is among the states with some of the highest dementia incidence in the country, particularly in the Southeast region including North Carolina, South Carolina, Georgia, and Florida.

The dementia (specifically Alzheimer’s) rate in Oregon for the population aged 65 and older generally ranges from about 9.0% to 11.0%, varying by county with some counties like Union County reaching around 11.0% prevalence.

Interestingly, Northwestern Texas, where lithium in well water is higher than average, has an elevated dementia rate (approximately 18% above the Mid-Atlantic baseline), which is higher than many areas but generally lower than Florida’s 12.5% dementia prevalence among those 65+, consistent with regional differences found across the U.S. The overall majority of Texans get drinking water from regulated public supplies rather than individual wells. Public municipal water systems in Northwestern Texas generally have lithium concentrations in treated drinking water that closely mirror the lithium levels found in source water, which primarily comes from groundwater or surface water sources. This is because lithium is a conservative element that is not effectively removed by conventional drinking water treatment processes. Thus, there is not a clear direct inverse relationship between dementia and lithium in drinking water in all cases.

Ideal Amount of Daily Lithium Orotate Supplement

There is no standard official guideline for lithium supplementation, as lithium is a trace element naturally found in food and water, and thus no universally established daily recommended intake exists. The average lithium intake in the U.S. from food and water is estimated to be approximately 0.5 to 3 mg per day, with some provisional recommendations suggesting a dietary requirement of about 1 mg per day for adults. In terms of supplementation, ionic or plant-based lithium supplements commonly provide around 0.3 to 0.6 mg of elemental lithium daily, whereas lithium orotate supplements typically contain higher amounts, often dosed at 5 mg or more of elemental lithium per day depending on individual tolerance and condition[22].

Regarding safety considerations, lithium supplements should be avoided during pregnancy and breastfeeding because lithium is excreted in breast milk and adverse effects have been reported in infants exposed this way, particularly with lithium carbonate or citrate use. Kidney safety is an important concern with lithium; the risk of nephrotoxicity significantly increases when serum lithium levels exceed about 0.8 mEq/L, and chronic exposure above this level, especially with episodes above 1.0 mEq/L, raises the chance of lasting kidney damage. Safe long-term lithium use usually entails maintaining serum lithium concentrations between 0.6 and 0.8 mEq/L or lower with regular monitoring to prevent toxicity[20].

To provide context, therapeutic lithium treatment for psychiatric disorders typically involves much higher doses, with daily lithium carbonate doses around 300 mg or more that aim to maintain serum lithium levels within the 0.6 to 0.8 mEq/L range. These doses carry a higher risk of nephrotoxicity and require medical supervision. In contrast, lithium orotate supplements taken at low doses—generally between 5 and 20 mg elemental lithium daily—are far below these therapeutic levels and have minimal or no reported kidney toxicity or serious adverse effects. The typical lithium obtained from diet and water (~0.5 to 3 mg daily) results in negligible serum lithium impact. Therefore, even a lithium orotate dose of about 6 mg per day is considered low and generally safe for long-term kidney health[21].

In summary, low-dose lithium supplementation such as lithium orotate at 5 to 20 mg elemental lithium daily is well below clinical therapeutic doses, making it generally safe with respect to kidney function. However, lithium supplements should be avoided during pregnancy and lactation due to potential risks. Nephrotoxicity concerns primarily relate to much higher doses used in psychiatric treatment rather than these low supplemental doses. As always, it is important to consult a healthcare professional before beginning any lithium supplementation, especially if there are pre-existing kidney issues or other health concerns.

Key Takeaways

Lithium naturally occurs in the brain at low but essential levels and supports major brain cell functions.
Lithium deficiency is an early event in Alzheimer’s disease, worsening amyloid-beta and tau pathology, inflammation, and cognitive decline.
Lithium orotate, a new lithium compound, can restore lithium levels, reduce brain pathology, and improve memory in animal models.
Lithium deficiency increases harmful enzyme activity (GSK3β) linked to neurodegeneration.
Preventing lithium deficiency through diet or supplements might offer a new strategy to prevent or treat Alzheimer’s.
Major natural dietary sources of lithium include leafy greens, nuts, legumes, some vegetables, cereals, and lithium-containing drinking water.
Current lithium therapies for bipolar disorder use higher doses than those suggested for brain health; low-dose lithium treatments within the physiological range appear effective and non-toxic in experiments.

This study opens a promising direction for Alzheimer’s research, emphasizing the importance of lithium in brain health and offering hope for new preventive and therapeutic options.[2][9][1][3][4][5][7]

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