Preprint says lithium ascorbate beat standard lithium in rodent stress tests

A new preprint on Research Square reports that lithium ascorbate outperformed lithium carbonate and other comparators in four rodent stress models, with anti-anxiety and antidepressant-like effects and less weight gain. The findings are preclinical, but they point to a possible alternative to prescription lithium if future human studies confirm the results.

Why it matters: - Lithium carbonate is a long-used prescription option for bipolar disorder and treatment-resistant depression, but its narrow therapeutic window and organ-related side effects limit use. - The preprint suggests lithium ascorbate could offer similar or better behavioral effects with fewer tradeoffs, including less weight gain. - If the results translate to humans, the compound could expand treatment options for conditions where lithium is effective but hard to tolerate.

What happened: - Researchers tested five substances in rodents: lithium carbonate, lithium orotate, lithium succinate, lithium ascorbate and ascorbic acid. - The study was published as a preprint on Research Square. - Lithium ascorbate showed the strongest anti-anxiety and antidepressant-like effects across four behavioral stress models.

The details: - Lithium carbonate is the standard inorganic lithium salt used in psychiatry for bipolar disorder and treatment-resistant depression. - Professor Olga Gromova, chief scientific officer for Normotim, said lithium carbonate is widely used because it is inexpensive and easy to produce, but the body does not fully absorb it. - Gromova said higher lithium carbonate doses can increase the burden on the kidneys. - Organic lithium salts such as lithium ascorbate, lithium citrate and lithium orotate are being studied as alternatives because they may be better absorbed and tolerated. - Lithium ascorbate combines lithium with ascorbic acid, or vitamin C. - The study used four behavioral stress models: open field test, swimming test, tail suspension test and simulated transport stress test. - In the open field test, lithium ascorbate and lithium orotate were compared head-to-head. - Lithium ascorbate reduced immobility, increased active coping, boosted locomotor and exploratory activity, and increased center entries. - Lithium ascorbate also reduced grooming and defecation and lowered post-stress adrenaline and norepinephrine. - Animals given lithium orotate gained 16.4% in body weight versus the control group. - Animals given lithium ascorbate stayed at 3.2% weight gain.

Between the lines: - The results add to interest in organic lithium salts as a way to separate lithium’s therapeutic effects from some of its tolerability problems. - The weight-gain difference could matter because metabolic side effects often limit long-term psychiatric treatment. - The evidence remains early. The work was preclinical, and rodent results do not prove clinical benefit in people. - The study also noted limitations including small samples, unequal elemental lithium exposure, differences in species, dosing and administration, repeated-testing effects and indirect stress markers.

What's next: - Human studies would be needed to determine whether lithium ascorbate is safe, effective and appropriately dosed in clinical settings. - Future research will also need to test whether the apparent advantage over lithium carbonate holds up outside rodent models. - The preprint suggests lithium ascorbate is a candidate for further development, not a replacement for prescription lithium today.

The bottom line: - Lithium ascorbate looked stronger than standard lithium options in these animal tests, but the findings are still early and not enough to change treatment practice.