Preclinical Studies of Lithium Ascorbate: Proven Safety
Lithium ascorbate is an innovative lithium salt where lithium ions are bound to ascorbic acid (vitamin C). It has been studied for safety in rats, mice, guinea pigs, and rabbits to find proper dosing that doesn’t cause any harm to body systems.
How Were The Experiments Done?
Researchers observed animals for up to seven months to demonstrate short-term and long-term safety. During the studies, animals were fed or injected with different doses of lithium ascorbate to identify a safe range of intake.
The studies were conducted in a certified laboratory following internationally recognized standards of Good Laboratory Practice.
Low Doses Are Safe To Take With Long-Term Daily Use
The accumulation level of lithium ascorbate was defined as moderate. It means that the substance can build up over time if moderate to high doses are taken regularly.
Lithium ascorbate also showed moderate toxicity, which means that a very high single dose can be lethal, while moderate and low doses are well tolerated.
Moderate toxicity and moderate accumulation are not dangerous in case of lithium ascorbate. A person would have to take very large doses of the supplement to feel negative side effects.
What Are The Safe Limits For Humans?
For an adult, it is safe to take 5 to 169 mg of elemental lithium a day — 5 to 34 Normotim tablets.
Conclusion
At low daily doses, lithium ascorbate has shown a strong safety profile:
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Does not cause allergic reactions
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Does not suppress normal behavior
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Does not affect the heart or blood circulation
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Does not influence metabolism
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Does not harm reproductive or genetic health
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Does not affect the brain, liver, kidneys, pancreas, lungs, or digestive system
Do You Want To Crunch Some Numbers?
We summarized each study below. If you are curious to see even more scientific data, follow the links in the table and read full texts of the studies.
Preclinical Study Summaries
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№ |
Study Title |
Summary |
|
1 |
Rats received single oral doses up to 8000 mg/kg. Lethal Dose 50 (LD₅₀) was over 6000 mg/kg, which places lithium ascorbate in the low-toxicity category (Class 5). Most deaths occurred at doses ≥6000 mg/kg, with symptoms such as lethargy, diarrhea, and cardiac overload. This suggests excellent safety for standard human use, where doses are typically thousands of times lower. |
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2 |
In mice, LD₅₀ was similarly high: 6140–6920 mg/kg. Toxic signs like ruffled fur and decreased activity appeared only at very high doses. No chronic damage observed in surviving animals. This confirms cross-species tolerance and low acute toxicity. |
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3 |
Even when injected directly into the bloodstream, lithium ascorbate showed low toxicity up to 3000 mg/kg. LD₅₀ ranged between 3225–3625 mg/kg. Minor side effects like fatigue or respiratory depression appeared only at near-lethal levels. This supports the compound's systemic safety. |
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4 |
Rats received gradually increasing daily doses for 21 days. Toxicity emerged only after 10+ days of high dosing. All animals died by day 21, confirming the existence of moderate cumulative toxicity (Fcum = 3.74). This is expected for bioactive ions like lithium but indicates long-term safety in clinical microdosing. |
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5 |
A single 1000 mg/kg oral dose was tracked across 11 tissues. The peak blood level was reached at 1.5 hours (Tmax), and the compound remained in the body for over 140 hours (T½). Lithium concentrated in the brain, aorta, bones, and adrenal glands, indicating a beneficial depot effect for neurological and vascular support. |
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6 |
Over a 6-month daily regimen, rabbits showed no mortality or organ pathology. Weight gain, behavior, and blood parameters remained normal. This suggests the compound is safe for long-term use, even in higher species. |
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7 |
In a broad toxicological screen, lithium ascorbate did not cause genetic mutations, fertility issues, or immune disruption. Some GI irritation was noted at high doses, but no systemic or teratogenic effects occurred. This validates its safety profile for reproductive and long-term human exposure. |
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8 |
Tests in guinea pigs and mice found no immediate or delayed allergic reactions. Lithium ascorbate did not act as an allergen or sensitizer, making it suitable for use in sensitive populations. |
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9 |
Rats receiving 10–15× therapeutic doses were tested for neurological, cardiac, and respiratory functions. No adverse effects were found. Open field and Irwin battery tests showed normal behavior and physiology, confirming multi-system safety. |
Principle of Human Dose Calculation
To assess potential risks and determine the therapeutic safety zone, preclinical doses were recalculated into Human Equivalent Doses (HED) using the formula approved by FDA:
HED (mg/kg) = Animal dose (mg/kg) ÷ Conversion factor (Km)
Km values:
• Mouse = 12.3
• Rat = 6.2
• Rabbit = 3.1
• Human = 37 (reference)
Key Definitions
LD₅₀ — the amount of a substance that causes death in 50% of test animals. The lower the LD₅₀, the more dangerous the substance.
IV (intravenous) — a way to deliver the substance by injecting it directly into the bloodstream.
Cumulative dose — the total amount of a substance given to an animal over time. Cumulative dose determines whether repeated doses can cause harm.
Pharmacokinetic dose — a dose given to an animal during the study to analyze how it is absorbed, distributed, stored, and eliminated.
Chronic safe daily dose — a dose of a substance that can be given every day over a long period of time without causing harm.
Systemic safety margin — the difference between the therapeutic dose and a dose that can cause harm. The wider the margin, the safer the substance is considered to be.
Results of Key Preclinical Studies
The table below shows results from studies identifying which doses were considered dangerous or safe. Dosing is normalized for a 60 kg (132 pounds) adult.
|
Parameter |
Lithium Ascorbate (mg) |
Elemental Lithium (mg) |
Equivalent Normotim Tablets (5 mg Li⁺) |
|
LD₅₀ (oral, rats) |
58,080 |
2,521 |
504 |
|
LD₅₀ (oral, mice) |
31,680 |
1,374 |
275 |
|
LD₅₀ (IV, rats) |
32,880 |
1,427 |
285 |
|
Cumulative dose (21 days) |
174,060 |
7,555 |
1,511 |
|
Pharmacokinetic dose (1 administration) |
9,660 |
419 |
84 |
|
Chronic safe daily dose |
3,900 |
169 |
34 |
|
Systemic safety margin |
2,880 |
125 |
25 |
|
Normotim (1 tablet/day) |
115 |
5 |
1 |
Key Findings
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Wide safety margin
When animals were given 30 – 50 times higher doses than a therapeutic dose, they showed no toxic effects in behavior or health. LD₅₀ (the dose that kills 50% of animals) is 2,521 mg of elemental lithium or 500 Normotim tablets meaning it is moderately toxic and is safe at low doses.
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Safe with long-term use
Even after giving animals very high doses daily for 6 months, no tissue damage or health issues were found.
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Therapeutic dose is far below risk levels
The typical human dose (5 mg/day) is hundreds of times lower than the levels that didn’t cause harm in animals.
Lithium ascorbate represents the next generation of lithium compounds: effective, non-toxic, and suitable for long-term use as a source of an essential nutrient. Its safety is confirmed by multiple preclinical studies. The dosage of 115 mg lithium ascorbate or 5 mg elemental lithium a day, as found in 1 Normotim tablet, is far beyond any risk thresholds.