Beyond Lithium is Lithium Orotate – A remarkable and superior support and protection for the brain

Lithium Orotate is a simple chemical salt (a salt of orotic acid and Lithium) - one of a number of different naturally occurring forms of Lithium. Two of these salts, Lithium carbonate and Lithium citrate are available as prescription forms of Lithium. Unfortunately, this fact has given rise to some confusion and has resulted in many people referring to Lithium as a drug. This isn’t correct - Lithium is not a drug at all but a naturally occurring mineral that belongs to the same family of minerals as sodium and potassium.

Lithium Orotate is popular naturopathic form of Lithium. You may have heard of it described as herbal Lithium, natural Lithium or homeopathic Lithium. It is generally marketed as a dietary supplement and can be used in small doses to treat a whole host of different conditions including bipolar and unipolar depression, attention deficit hyperactivity disorder (ADHD), stress, post traumatic stress disorder (PTSD), aggression, alcoholism and Alzheimer’s Disease.

However, before we delve too deeply into how Lithium Orotate can benefit us, many will be aware that there has been some controversy over the years surrounding the use of Lithium which has given it a questionable, albeit unwarranted, reputation in some quarters. It is probably best to address the question of this controversy at the outset.

1 The Lithium Discussion

Lithium has been in use for many decades. Indeed, the use of Lithium in psychiatry goes back to the mid-19th century although this early work was soon forgotten(1). In the 1930s and 1940s Lithium, in the form of Lithium chloride, was sold as a salt substitute for people on low salt diets. Unfortunately the amount of Lithium used for this application proved to be toxic - and even fatal in some cases. Consequently, and not surprisingly, the use of Lithium fell out of popularity.

However, this was unfortunate timing because in the late 1940s an Australian physician, John Cade, reintroduced Lithium as an effective treatment for what was then called manic depression and is now known as bipolar disorder. But, because of the earlier problems with Lithium chloride, it was not until the 1970s that the US Food and Drugs Administration (the FDA) approved Lithium for medical treatment. By the mid 1990s Lithium had finally been included in a list of 18 elements that might be important for human nutrition.

Unfortunately, although it appears that Lithium’s star is finally rising, controversy still remains. One problem is the potential toxicity of the high doses of Lithium citrate and Lithium carbonate given to achieve therapeutic effect (something which we will return to in more detail later). Although this does not apply to Lithium Orotate, many people incorrectly assume that it does.

The situation has not been helped by the somewhat mixed messages that researchers have produced. In one study involving rats who were treated with Lithium Orotate, the researchers demonstrated that Lithium Orotate had an adverse impact on the rats’ kidneys when compared with conventional Lithium carbonate. This led the researchers to conclude that “it seems inadvisable to use Lithium Orotate for the treatment of patients”(2). Not surprisingly this study did considerable damage to Lithium Orotate’s reputation. But, as critics of this study point out, the amounts of Lithium Orotate injected into the rats were relatively huge - and yet , as we will see later, only small doses of Lithium Orotate are required to achieve the same benefits as Lithium carbonate, so there was little point in carrying out tests using the same large amounts!

The other major problem with Lithium therapy stems from people's perception of it. This arises because Lithium is best known for its use as a treatment for bipolar disorder. As we are all too aware mental illness such as bipolar disorder carries with it a stigma and this stigma seems to extend to the therapies used to treat such conditions as well.

2 What is Lithium used for?

As mentioned above, Lithium can be used to treat a range of different conditions. But what is probably even more exciting , certainly in terms of anti-aging medicine, is that it can offer significant neuroprotective benefits which may be able to help halt, or even reverse, the mental decline that is so often associated with old age. Let’s now turn to the different uses for Lithium.

2.1 Mental illness treatment: Particularly bipolar disorder

As this use of Lithium is the most well known it would seem the most logical place to start. Bipolar Disorder is an illness that results from an imbalance of chemicals in the brain that can cause extreme fluctuations in mood. Although everyone experiences happiness and sadness, people with bipolar disorder experience these feelings at a greatly exaggerated level. Their moods can swing from the depths of depression to the heights of mania. The depressive episodes are characterized by such things as a persistent low mood, loss of self esteem, lethargy and feelings of helplessness whereas during periods of mania the sufferer is likely to display symptoms such as abnormal and persistently elevated mood, lack of sleep, hyperactivity and inflated self esteem.

Lithium works by having a significant stabilizing effect on mood swings, depression and mania and acts as an effective mood enhancer in 70-80% of bipolar patients. Indeed, Lithium is so successful in treating patients suffering from manic/depressive conditions that it is the treatment of choice for patients with recurring bipolar disorder.

Unfortunately, bipolar patients are at a heightened risk of suicide during their depressive episodes. Again Lithium can help. Researchers have been able to show that the suicide rate amongst bipolar patients given long-term Lithium treatment is markedly lower than that of patients not receiving Lithium(3,4).

2.2 Unipolar Disorder treatment

But it is not just bipolar disorder that responds well to Lithium therapy. Trials have shown that Lithium is also effective in the management of unipolar disorder (sometimes referred to as major affective disorder)(5) and Lithium therapy has been successfully for this condition for many years throughout Europe. Like its sister condition bipolar disorder, unipolar disorder is characterized by severe and debilitating episodes of clinical depression or major depression. But unlike bipolar disorder, unipolar disorder does not have periods of manic symptoms only depressive ones. Patients that suffer from this disorder may become withdrawn, hopeless and overwhelmed and experience significant disruption in their work, social and family life. They are no longer able to enjoy the things they used to do and, in severe cases, it may lead to suicide.

2.3 Lithium Orotate as a treatment for alcoholism

Lithium Orotate may also be useful in the treatment of alcoholism. In one study(6), 42 alcoholic patients (33 males and 9 females) were treated with Lithium Orotate during an alcohol rehabilitation program in a private clinical setting over a period of at least six months. The patients presented with a whole range of health problems attributable to their chronic alcoholism such as liver dysfunction and seizures and 36 of them had already been hospitalized at least once for the management of their alcoholism. During the treatment period, the patients each received 150mg daily of Lithium Orotate. The patients also received calcium orotate (for hepatic involvement), magnesium orotate, bromelaine, and essential phospholipids (for cardiac problems), and the appropriate supportive measures were taken where required.

Despite the fact that the cohort consisted of chronic alcoholics, many of whom had a history of failed attempts to treat their addiction, Lithium Orotate proved to be useful as the main pharmacologic agent for the treatment of their condition. Ten of the patients had no relapse for over three and up to 10 years, 13 patients remained without relapse for 1 to 3 years, and the remaining 12 had relapses between 6 to 12 months. In addition, Lithium Orotate proved to be safe with only minor side effects reported in 8 patients. These 8 patients developed loss of appetite, mild apathy or muscle weakness. Their side effects dissipated when their dosage was reduced to 4/5 times a week rather than daily.

And not only does Lithium Orotate help to tackle the addiction, it also appears to be useful in treating alcohol-related symptoms such as liver dysfunction, liver and lung cancers, headaches, seizure disorders, hyperthyroidism, affective disorders and Meniere's syndrome (a disorder of the inner ear that can affect hearing and balance).

2.4 Treatment as a neuro-protective agent

Fortunately, despite the fact that Lithium has been used for so many years in the treatment of bipolar depression, research into its use in this area has continued. An amazing bi-product of this research has been the remarkable discovery that Lithium possesses incredible neuro-protective properties.

In the late 1990s researchers based at Wayne State University School of Medicine, Detroit, Michigan who had been studying the effects of Lithium in relation to bipolar disorder, discovered that not only does Lithium appear to help to protect brain cells from premature death, it may even cause brain cells to regenerate if they are lost through disease(7,8,9). The researchers reported that 8 out of 10 patients who had received Lithium therapy showed, via MRI scans, an average 3 percent increase in brain grey matter in just four weeks(9).

To put the significance of these discoveries in to some sort of context, you need to remember that up until this point in time medical experts believed that once our brains had matured, no more brain cell growth was possible. Countless studies, scans and autopsies had all concluded that human brains shrink as they age.

2.5 Lithium as a treatment for other neuro-protective conditions

Lithium also appears to enhance nerve cell DNA replication. DNA replication is an essential first step in the formation of new cells. These discoveries may prove to be of crucial importance in relation to neurodegenerative diseases such as Alzheimer’s Disease and senile dementia which are characterized by brain cell death.

And if being able to regenerate brain mass wasn’t enough, Lithium may also help to protect the human brain from toxin damage. Everyday our brains are exposed to the risk of this sort of damage. Toxic molecules are formed naturally during the course of normal brain metabolism and eventually they begin to wear away brain mass - all part of the natural aging process. Lithium appears to be able to offer protection against such damage.

In addition, Lithium may be able to offer neuro-protection against the damage that can be caused from other sources too such as prescription medications and strokes. For example, anti-convulsant medications can have a negative impact on the brain and cause abnormal levels of brain cell death. But Lithium can help by offering significant protection against this type of cell death(10).

The neuroprotective effects Lithium are also known to extend to hippocampus - the area of the brain in which memories are stored. Unfortunately, the hippocampus is one of the first areas of the brain to suffer damage in Alzheimer’s Disease, with memory problems and disorientation often appearing as some of the first symptoms of the disease. By offering protection to the hippocampus and preventing its decline, Lithium may again be of use in the treatment of Alzheimer’s Disease and may be able to help protect you from senile dementia.

The key to Lithium’s neuro-protective benefits appears to lie in its action upon two different proteins - Bcl-2 (named for the B-cell lymphoma/ leukemia-2 gene) and GSK-3b (glycogen synthase kinase 3b). Bcl-2 is an extremely beneficial protein because it protects brain cells from a variety of injuries, including chemical oxidants and ionizing radiation. Researchers have demonstrated that Lithium increases concentrations of Bcl-2 in brain tissue - the first substance known to do this. On the other hand, GSK-3b can be destructive. It appears to be associated with the production of neuro-fibrillary tangles which are a key feature of Alzheimer’s Disease. Lithium acts to reduce levels of this protein.

In the light of the persuasive research that has already been established in favour of Lithium as an important neuro-protective agent, world renowned anti-aging medicine expert Dr Jonathan Wright states that he is now “convinced that Lithium is the anti-aging nutrient for humans.”(10).

Undoubtedly, further research is still needed to enhance our knowledge of Lithium and its role as a neuro-protective agent. Over the next few years hopefully we will begin to understand more about the role of this truly remarkable mineral and its ability to protect and support the brain. Indeed, in May 2009 results of a 7 year longitudinal study into Lithium led researchers to conclude that “future treatments that more directly target molecules in critical central nervous system pathways hold promise as novel, improved, long-term treatments for mood disorders as well as some neurodegenerative conditions, such as Alzheimer's disease”(11).

2.6 Lithium as an Aluminium Chelator treatment

Chelation is the name given to the therapy whereby chelating agents are administered in order to remove toxic levels of heavy metals from the body. The idea behind the therapy is that the chelating agents bind to the toxins you are trying to remove and form compounds that can then be safely excreted from the body via the blood stream.

Although aluminium is not technically a heavy metal, it can still be toxic. Unfortunately, you can’t avoid exposure to aluminium - it’s the third most abundant element on earth and is readily available for human ingestion through all manner of means. For example aluminium is used in food additives, antacids, buffered aspirin, nasal sprays, and antiperspirants; It is found in drinking water; It forms part of vehicle exhaust fumes and tobacco smoke and it is used in the kitchen via such things as aluminium foil, aluminium cookware and aluminium cans.

Around 20 years ago studies suggesting a possible link between aluminium and Alzheimer’s Disease began to emerge. Researchers had discovered what appeared to them to be significant amounts of aluminium in the brain tissue of Alzheimer’s patients. Unfortunately this association between aluminium and Alzheimer’s Disease is not clear cut because aluminium has also been found in the brains of people who did not have Alzheimer’s Disease. Naturally this has caused some controversy but most experts agree that aluminium may be an important factor in the dementia element of the disease and the area is one in which further research is required.

In any event, in order to remove aluminium from the body a chelating agent must be used and this is where Lithium once more steps up to the mark. As far back as 1970s Professor Johan Bjorksten (the creator of the cross-linkage theory of aging) had successfully demonstrated Lithium’s effectiveness as an aluminium chelator and crosslinkage inhibitor. Indeed, Bjorksten stated that Lithium was the most effective electrolyte for aluminium detachment(12).

2.7 Other uses for Lithium treatment

With Lithium being so effective in the treatment of manic/depressive illnesses, it’s clear that research until fairly recently has perhaps overlooked examining whether this remarkable mineral can benefit us in other ways. As knowledge of its role beyond the treatment of such illnesses becomes clearer, we will undoubtedly discover more about the positive effects of Lithium on the human body. For example, Lithium Orotate has already been used successfully alleviating the pain from migraine and cluster headaches, treating low white blood cell counts and juvenile convulsive disease. People suffering from myopia (short-sightedness) and glaucoma may also benefit from the slight dehydrating effect of Lithium on the eye. This can result in improvements in vision and the reduction of intraocular pressure.

Lithium may even be able to moderate people’s behaviour. For example after reviewing data from 27 Texan counties covering a ten year period, researchers found that the incidence of crimes including homicide, rape and burglary, as well as suicide rates and drug use were significantly lower in counties whose drinking water supplies contained 70-170 micrograms of Lithium per litre than those with little or no Lithium in their water. This led the researchers to conclude that “Lithium at low dosage levels has a generally beneficial effect on human behaviour.”(13).

3 Why Lithium Orotate is superior

At this point you may be wondering why you should take Lithium Orotate rather than other forms of Lithium salts? The big difference is bioavailability - that is to say the degree at which, or the rate at which, a drug or other substance is absorbed by the body or becomes available at the targeted place within the body. Lithium Orotate has superior bioavailability compared with other forms of Lithium salts, easily crossing the blood brain barrier. This has made it a popular and successful supplement and one that is available without the need for a prescription.

The superior bioavailability of Lithium Orotate enables Lithium Orotate to transport Lithium directly to the membranes of mitochondria, lysosomes and the glial cells. Mitochondria are the powerhouses inside cells that take in nutrients, break them down and produce energy. Lysosomes are organelles found within cells that break up food so that it is easier to digest. Glial cells are the non-neuronal cells of the nervous system. Their role is to provide support and protection for neurons, the other main type of cell in the nervous system.

The upshot of this greatly increased bioavailability is that much lower doses of Lithium Orotate can be used to achieve the same therapeutic effects as much greater doses of other forms of Lithium and this difference is crucial. Although Lithium is extremely useful in the treatment of manic/depressive illnesses, its pharmaceutical (i.e. prescription) versions (Lithium carbonate and Lithium citrate) are poorly absorbed by the cells of the body. This creates a significant problem because it is within cells that Lithium exerts its therapeutic effects. The result is that, in order to have any therapeutic benefit, pharmaceutical forms of Lithium have to be administered in such high doses that blood levels of Lithium increase to such an extent that they border on being toxic.

Symptoms of the toxic effects of Lithium can include thirst, frequent urination, hand tremors, frequent urination, nausea, vomiting, drowsiness, blurred vision and muscular weakness. As a result patients using Lithium therapy in such circumstances have to be carefully monitored for signs of Lithium poisoning. This constant need for monitoring coupled with the high risk of developing side effects mean that some patients simply cannot tolerate treatment with the pharmaceutical versions of Lithium, even though such treatment is highly effective.

But with the ability to increase the bioavailability of Lithium many times over, Lithium Orotate does not encounter such problems. The superior bioavailability means that the therapeutic dosage of Lithium Orotate is much lower than those of pharmaceutical forms of Lithium(14). So, for example, a daily dose of 900-1800mg of Lithium carbonate or Lithium citrate, might only require a 150 mg per day dose of Lithium Orotate to achieve the same therapeutic effect. At such low doses the likelihood of experiencing any potential adverse Lithium side effects is drastically reduced and the need for monitoring Lithium levels in the blood is alleviated. Of course all medications and supplements carry with them the potential for side effects to occur but, even if you were unfortunate enough to suffer from any side effects - and it should be remembered that all medicines carry with them the potential for side effects to develop - the severity of these side effects would also be ameliorated with any side effects being far milder in nature.

4 Conclusions on Lithium Orotate

In terms of anti-aging, Lithium Orotate is a safe nutritional supplement that offers significant neuro-protective properties that can help to support the health of your brain as you age and may help to protect you against the development of Alzheimer’s Disease and other neuro-degenerative diseases.

With its superior bioavailability, you can benefit from the advantages of Lithium in much lower, and much safer, doses secure in the knowledge that these lower doses are just as effective as the much higher, and potentially more dangerous, doses found in pharmaceutical versions of Lithium.

5 References

1. Shorter E. The history of Lithium therapy. Bipolar Disord. 2009 Jun;11 Suppl 2:4-9.
2. Smith DF, Schou M. Kidney function and Lithium concentrations of rats given an injection of Lithium Orotate or Lithium carbonate. J Pharm Pharmacol. 1979 Mar;31(3):161-3. Retrieved 18 April 2007
3. Schou M. Perspectives on Lithium treatment of bipolar disorder: action, efficacy, effect on suicidal behavior. Bipolar Disord. 1999 Sep;1(1):5-10.
4. Schou M. Suicidal behavior and prophylactic Lithium treatment of major mood disorders: a review of reviews. Suicide Life Threat Behav. 2000 Fall;30(3):289-93.
5. Souza FG, Goodwin GM. Lithium treatment and prophylaxis in unipolar depression: a meta-analysis. Br J Psychiatry. 1991 May;158:666-75.
6. Sartori HE. Lithium Orotate in the treatment of alcoholism and related conditions. Alcohol. 1986 Mar-Apr;3(2):97-100.
7. Fugate L. Lithium's Potential Role in Preventing Alzheimer's Disease. http://intelegen.com/nutrients/Lithium.htm
8. Manji HK, Moore GJ, Chen G. Lithium at 50: have the neuroprotective effects of this unique medication been overlooked? Biol Psychiatry. 1999 Oct 1;46(7):929-40.
9. Moore GJ, Bebchuk JM, Wilds IB, Chen G, Manji HK. Lithium-Induced Increase in Human Brain Grey Matter, The Lancet, Oct. 7, 2000, vol. 356, pp. 1241-1242.
10. Wright JV. The Misunderstood Mineral Part 1. Reprinted from “Nutrition and Healing” published online at http://www.tahoma-clinic.com/Lithium1
11. Moore GJ, Cortese BM, Glitz DA, Zajac-Benitez C, Quiroz JA, Uhde TW, Drevets WC, Manji HK. A longitudinal study of the effects of Lithium treatment on prefrontal and subgenual prefrontal gray matter volume in treatment-responsive bipolar disorder patients. J Clin Psychiatry. 2009 May;70(5):699-705.
12. Bjorksten J. Pathways to the decisive extension of the human specific lifespan. J Am Geriatr Soc. 1977 Sep;25(9):396-9.
13. Wright JV. The Misunderstood Mineral Part 2. Reprinted from “Nutrition and Healing” published online at http://www.tahoma-clinic.com/Lithium2
14. Kling MA, Manowitz P, Pollack IW. Rat brain and serum Lithium concentrations after acute injections of Lithium carbonate and orotate. J Pharm Pharmacol. 1978 Jun;30(6):368-70.

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