When I first wrote about microdosing lithium in October 2022, I had no idea of the widespread interest in this topic and the dearth of information available on it. I received a lot of emails with questions that were not specifically addressed in the original article. Hence, in this article, I will answer some of the most commonly asked questions, along with a couple case studies, and discuss why I believe lithium will continue to have an important role in the future.
There were many questions about the supplement lithium orotate. As I mentioned in the earlier article, lithium orotate is over the counter and available in much smaller doses than the prescription versions lithium carbonate and lithium citrate. I have collected several articles about lithium orotate over the past 25 years but unfortunately there has been little or no financial incentive for experimental research to answer the question, unquestionably, of efficacy for mood issues. My clinical bias is to recommend low dose lithium carbonate (150-300 MG QDAY) for mood issues for anyone with a psychiatric disorder, especially bipolar depression or someone with a first degree relative who developed Alzheimer’s Disease before 70 years old. If a person is interested in supplementing with lithium to prevent the risk of Alzheimers without a psychiatric history, then lithium orotate is a good option with the dosing between 1 MG-5 MG every day. Certainly, you can supplement with lithium orotate for some mild mood issues but the dose is probably going to have to be closer to 150 MG to have any beneficial effect. I would not recommend lithium orotate for anyone with Bipolar I Disorder.
I did notice anecdotally that people that are supersensitive to all supplements and medications can develop side effects with higher doses of lithium orotate; one person noticed dizziness and low blood pressure at 20 MG a day of lithium orotate but had no issues at lower doses. Even though lithium orotate is over the counter, I also believe it’s a good idea to check with your primary care doctor to be sure your kidneys are not compromised (a creatinine level from a standard blood panel answers the question) and consider getting an EKG if you are over 50 years old (if there is a preexisting arrhythmia which would need to be treated before starting lithium).
As with any supplement, I recommend looking for 3rd party testing approval on the label when purchasing lithium orotate which includes: GMP (Good Manufacturing Practices), NSF (National Sanitation Foundation), USP (United States Pharmacopoeia), CL (Consumer Lab). That will give some peace of mind that a product contains what’s on the label. Some reliable brands include: Ortho Molecular Products, Designs for Health, and Complementary Prescriptions.
In my own clinical work for microdosing lithium carbonate, there are have been 2 common scenarios about how I decide who is a good candidate.
Too many side effects at higher doses of lithium (> 600 MG)
For example, I work with a young woman with Bipolar II Disorder who when I first met her was taking an antipsychotic medication, aripiprazole, for her mood but she never felt like herself on it. As an aside, she eats fairly healthy on a Mediterranean diet and I will discuss later in the article why I believe that’s important. She was eventually hospitalized after being non-adherent with the antipsychotic medication and then placed on lithium carbonate 900 MG QDAY with a stable mood. However, she struggled with hand tremor, frequent urination at night, and concerns about long term effects on her kidney. We continued to taper her dose downward and she even came off lithium for a couple months before realizing she was becoming more depressed. In the end, she agreed to go back on low dose lithium carbonate 150 MG and another mood stabilizer, lamotrigine, and has been very stable over the past 2 years without side effects.
Genetic testing results show an ANK3 variant
The ANK3 gene codes for Ankyrin G which is responsible for the clustering of sodium channels and having a variant (C/T or T/T instead of the normal C/C) can be associated with Bipolar Disorder, stress intolerance and/or anger. This gene can be found on 23&me, Ancestry DNA, and other commercial panels. Just to be clear, having one variant for ANK3 only means a person has a 30% increased risk of Bipolar Disorder and is not diagnostic. However, it turns out that lithium (and some epileptic mood stabilizers) helps stabilize and anchor the sodium channel properly and can be useful with mood issues that are not necessarily Bipolar Disorder.
One recent example in my private practice is a 30 year old man who presented with treatment resistant depression but there was a concern from his previous psychiatrist about mood instability based upon his having become briefly hypomanic after receiving IV Ketamine treatments. I went ahead and ordered psychiatric genetic testing which revealed an ANK3 variant. He agreed to a trial of lithium carbonate 150 MG and has been stable on it ever since. Even though he never presented with classic bipolar symptoms, I considered him a good candidate based upon his genetic results.
The future of lithium
Lithium has a very interesting history and in the mid-19th century, the very first pharmaceutical use of lithium was to reduce uric acid. High uric acid is associated with gout and is treated nowadays with allopurinol. In the 1940s, an Australian psychiatrist, Dr John Cade, hypothesized that the same condition involving uric acid might lie behind his manic patient’s “psychotic excitement” and began treating patients with lithium carbonate and lithium citrate, both of which lower uric acid. People who have bipolar illness naturally have high uric acid which leads to insulin resistance (diabetes) and to hypertension. Fructose leads to the production of uric acid so that’s why I believe a healthy diet with low sugar intake is an important lifestyle piece for stabilizing mood if a person wants to only take small doses of lithium.
A more recent theory about bipolar illness is that the mitochondrial function is broken. You may remember from science class that mitochondria serve as the energy production (ATP) part of the cell and there’s some evidence that bipolar folks are just not making enough of it. More specifically within the mitochondria, adenosine modulation and reduction of uric acid that are manipulated by the purinergic system are broken. However, it turns out that lithium has effects on this very part of the biology that is broken which would make lithium a disease modifying treatment.
Twenty years ago, lithium was used much more and antipsychotics much much less. Now, antipsychotics are what 60% of bipolar clients take. The literature supports that people taking lithium feel like themselves and function well, and that those taking antipsychotics, after around 2 years, do not. People with bipolar type I are prone to being amotivational and to having poor dopamine tone to begin with, and then to give them an antipsychotic drug that reduces dopamine in the in prefrontal cortex is not optimal for daily functioning. Antipsychotics can also have a 20-40% risk of tardive dyskinesia not to mention other forms of movement disorders. I have to question in the long term if this is really worth it for someone that could potentially do even better on lithium and perhaps on a low dose without side effects. For that reason, I believe no matter how many new antipsychotic medications come out to treat mood disorders, lithium will continue to have a unique role as a disease modifying treatment for mood issues.