LITHIUM

– Lithium Orotate (5mg daily) has been used by physicians as an antidepressant for a long time but it is important to use the right form of this mineral which is orotate. It helps boost serotonin, reduce stress and tension, improve mood, reduces mood swings, and boosts energy levels (>). A study in Greece found that lithium levels in drinking water ranged from 0.1 to 121 mg/l. Areas with higher levels of lithium in the natural water supply had lower suicide rates (>). According to another study, homicide rates are lower in areas with higher levels of lithium in the water supply (>).

– Methylcobalamin (form of vitamin B12) is another very important remedy which helped many people to get rid of depression, anxiety, chronic fatigue, insomnia, and low mood as deficiency of this vitamin is regarded as “rampant” today (>). B12 is involved in neurotransmitter function and research shows that low levels of this vitamin are linked to depressive symptoms. This is especially true for alcoholics and those who have been treated their depression with lithium as people who take long-term prescription levels of lithium for bipolar disorder tend to have lower serum levels of B12 (probably because more B12 is found in cells) (>). According to Dr Yasko “Lithium not only plays a role in mood, glutamate control and limiting aggression but also has been shown to be involved in B12 transport” (>). She recommends making sure your lithium level is balanced before supplementing with good B12 such as sublingual methylcobalamin. In addition to Dr Yasko’s clinical work associating B12 and lithium, there are some studies that seem to lead to the same conclusion (>).

 

 

LITHIUM

https://www.geneticlifehacks.com/a-little-lithium-and-b-12-makes-the-world-a-happier-place-for-some/

This article is referring to an over-the-counter mineral supplement of lithium orotate or lithium aspartate which is different than the large prescription doses of lithium carbonate used to treat bipolar disorder.

Lithium is a naturally occurring mineral that is found in drinking water and food. However, the concentration depends on this mineral content in the soil and water which may differ greatly.

On average we probably may get about 3-4 mg from food and water we drink.

Supplemental lithium orotate comes in 5mg and 10mg dosages.

Studies on lithium levels found naturally in drinking water:

  • A study in Greece found that lithium levels in drinking water ranged from 0.1 to 121 [mu]g/l). Areas with higher levels of lithium in the natural water supply had lower suicide rates. [ref]
  • Another study found that homicide rates are lower in areas with higher levels of lithium in the water supply. [ref]

What is the connection between lithium orotate, mood, and B-vitamins?

Dr. Amy Yasko explains on her website why she thinks some of us need and use more of the mineral lithium than others. She recommends checking lithium levels for all autistic children and suggests supplementing with low levels of lithium for MTR/MTRR mutations. Dr. Yasko states that “Lithium not only plays a role in mood, glutamate control and limiting aggression but also has been shown to be involved in B12 transport.”[ref]  She recommends making sure your lithium level is in balance before adding in B12.

In addition to Dr. Yasko’s clinical work associating B12 and lithium, there are several studies showing this as well.[ref]

  • People who take prescription levels of lithium long-term for bipolar disorder tend to have lower serum levels of B12 (thus more B12 in cells?) than people using other medications.[ref]
  • A study that analyzed lithium in hair samples in a variety of locations and populations  “suggests a role of lithium in the transport and distribution of vitamin B12.”[ref]
  • A recent study (Feb. 2020) finds that for animal-models of manic/depressive disorder, lithium works better in conjunction with folate (vitamin B9).[ref]

Why is vitamin B12 important to your mood?

Vitamin B12, along with folate, is essential for the production of tetrahydrobiopterin (BH4) which, in turn, is involved in the production of the neurotransmitters serotonin, melatonin, dopamine, norepinephrine, and epinephrine.[ref]

A deficiency of vitamin B12 has been shown to cause symptoms which “may include agitation, irritability, negativism, confusion, disorientation, amnesia, impaired concentration and attention, and insomnia; while psychiatric disorders that may be diagnosed in patients having vitamin B12 deficiency include depression, bipolar disorder, panic disorder, psychosis, phobias, and dementia”. [ref]

Does lithium orotate work for everyone?

On a personal note, one family member (who is homozygous for several of the snps below) found that supplementing with lithium orotate and B12 was extremely helpful and is no longer irritated by, well, everyone and everything. The rest of the family, without the homozygous SNPs, doesn’t really notice any difference when taking lithium orotate, showing once again that everyone is different. It is truly amazing, though, the difference it makes when you hit on the right food or supplement for your body and your genes.

Genetic Variants:

The MTR and MTRR genes are important in vitamin B12 usage in the methylation cycle.

Dr. Yasko also has a free video of a seminar where she lays out her research on the effects of lithium. She makes the case that lithium, through the inhibition of thioredoxin, can increase COMT, which is an enzyme that regulates and degrades dopamine, epinephrine, and norepinephrine.

Note: I want to be really clear here… This information is based on online recommendations for clinicians, such as Dr. Yasko. There are no research studies that specifically show that lithium orotate works to improve mood for people with these variants.

MTR Genetic Variants:

Members: See your data below

Check your genetic data for rs1805087 (23andMe v4, v5; AncestryDNA):

  • A/A: typical
  • A/G: increased enzyme activity, possibly responsive to lithium orotate supplements for irritability, anxiety
  • G/G: increased enzyme activity [ref] possibly responsive to lithium orotate supplements for irritability, anxiety

Members: Your genotype for rs1805087 is —.

The rs1805087 variant is also known as A2756G. The G allele causes an increase in activity, thus possibly causing a decrease in methyl groups available for other pathways to use and also using up methylB12 more quickly than normal. [ref]

MTRR Genetic Variants:

Methionine synthase reductase has several fairly common variants that affect the production of the MTRR enzyme which regenerates vitamin B12 (methylcobalamin) for use by MTR and other enzymes. The variant rs1801394 is also known as A66G, and it decreases this enzyme’s efficiency.  It is a fairly common variant which is carried by about half the population.

Check your genetic data for rs1801394 (23andMe v4, v5; AncestryDNA):

  • A/A: typical
  • A/G: somewhat decreased enzyme efficiency
  • G/G: decreased enzyme efficiency [ref][ref]

Members: Your genotype for rs1801394 is —.

COMT rs4680, Val158Met

One of the most studied variants of the COMT gene is rs4680, often referred to as Val158Met.  In looking at research studies, the G is “Val” and the A allele is usually noted as “Met”.

  • The G allele (Val) has higher COMT enzymatic activity, causing a more rapid breakdown of the neurotransmitters and thus lower levels of dopamine. In most populations, the G allele is the most common.[ref]
  • The A allele (Met) has lower COMT enzyme activity and thus higher levels of dopamine.  This variant of the COMT enzyme is said to have lower activity because it breaks down faster at normal body temperature.[ref]

Check your genetic data for rs4680 (23andMe v.4 and v.5; AncestryDNA):

  • G/G: higher COMT activity, lower dopamine & norepinephrine, higher pain tolerance (Val)
  • A/G: intermediate COMT activity (most common genotype)
  • A/A: 40% lower COMT activity, higher dopamine & norepinephrine, lower pain tolerance (Met), reduced stress resiliency

Members: Your genotype for rs4680 is —.

Lifehacks

Lithium Supplements

Lithium orotate and lithium aspartate are both available in health food stores and online in 5 mg – 20mg doses.

Natural Sources of Lithium:

Lithium occurs naturally in spring water in certain areas and can range from less than 1 mcg/l to well over 100 mcg/l.  It is also found in the soil and can be taken up by plants depending on the concentration in the soil. Here is a map of a few places in the US showing lithium levels in the well water.

A study in 1989 looked at the lithium levels in the water in 27 counties in Texas.  The study showed that counties that had water with higher lithium levels had significantly lower violent crime rates and suicide rates.  There have been several more studies completed more recently in other countries that show the same decrease in suicide and homicide with higher levels of naturally occurring lithium.

Lithium and Polyunsaturated Fatty Acids (PUFA):

Several studies have found that lithium reduces arachidonic acid (inflammatory polyunsaturated fatty acid) production in the brain.  One theory is that this reduction of neuroinflammation is a reason that prescription-strength lithium chloride works for bipolar disorder.  For more information about genetics and variants that affect the fatty acid composition, check out the article on Omega-3 vs. Omega-6 fats and your genes.

These two studies are worth reading if you are interested in the link between lithium and neuroinflammation:

Uses for high dosage lithium:
For well over a century, lithium has been used in high pharmacological doses (typically 300-1200+ mg per day) to treat bipolar disorder and other mood disorders.  It is also being investigated and used to slow the progress of ALS, dementia, and Alzheimer’s disease.

Studies on lithium carbonate (pharmacological doses for mood disorders) and genetic polymorphisms:

Safety of taking lithium:

Prescription levels of lithium do come with long-term side effects including higher risks of hypothyroidism and kidney problems.

  • Lithium toxicity profile: a systematic review and meta-analysis, 2012 — A meta-study on side effects from prescription dosages of lithium carbonate used for mood disorders showed that lithium increased the risk for hypothyroidism and weight gain. It also showed an increased risk of renal failure, with the overall risk being 0.5%.

Lithium orotate has one case study (of one patient):

  • Lithium toxicity from an internet dietary supplement, 2007 — case study of an 18-year-old who took 18 tablets of Find Serenity Now, each of which contained 120mg of lithium orotate.  She went to the emergency department with nausea and was discharged after a few hours to a psychiatric hospital.

A recent animal study showed that increasing zinc intake eliminated the deleterious thyroid effects from lithium carbonate. [ref]

Lithium in the News

There have been a couple of really good articles recently explaining the benefits of a little lithium.

Updated on 2/4/2019

 

 

 

 

Lithium Orotate

 

Written by Dr. Edward Group

 

https://globalhealing.com/natural-health/natural-mood-enhancers/#references

 

 

 

Lithium Orotate

Has your “get up and go” got up and left you? If stress is weighing you down, lithium orotate may help you reduce stress and let go of unwanted tension. Lithium orotate increases levels of happiness, calms mood swings, and even boosts your energy levels.[9] Global Healing’s Lithium Orotate can help bring calmness and clarity to your mind. Getting enough lithium in the diet has been linked to whole neighborhoods and groups getting along, with fewer issues.[9]

 

 

The health benefits of lithium orotate are causing an explosion in its popularity. I’ve been an advocate of lithium orotate for quite some time and have incorporated into some of my own formulations. A friend of mine, Dr. Mark Millar, is the leading authority on lithium orotate in the United States today. He published an eBook, Veteran Suicide Breakthrough: Revealing the Breakthrough Mineral for Suicide Prevention, PTSD and Depression ‘They Definitely’ Don’t Want You to Know About which is loaded with facts on lithium’s effects on the both body and brain. I’d really encourage you to check out his book, it’s powerful information you’re not going to hear from any mainstream source. I’d like to share a few of the shocking facts contained within the pages of Dr. Millar’s book but must reiterate that much of this is very controversial, disputed by the mainstream medical establishment, and should not be interpreted as claims, promises, or fodder to diagnose yourself. I am sharing this for informational purposes only! Lithium orotate is intended as a nutrient to supplement the diet. Its effects are nutritional. The statements in this article have not been evaluated by the Food and Drug Administration and this nutrient is not intended to diagnose, treat, cure or prevent any disease.

What Is Lithium?

  • “Technically, lithium is not a drug but a mineral, similar to salt.” -VA Research Currents
  • “In fact, lithium isn’t a drug at all. It’s actually a mineral — part of the same family of minerals that includes sodium and potassium.” -Jonathan Wright, M.D., author of “The Importance of Lithium Supplementation”
  • “Shocking but true — lithium is an essential trace element.” -Emily Deans, M.D., (Harvard trained psychiatrist) author of “Could You Have a Lithium Deficiency?”
  • “Lithium is an essential micronutrient… It is present in all organs and tissues in the body. It has similar chemical properties to that of calcium and magnesium.” -Mark Hyman, M.D., best-selling author of “The UltraMind Solution”
  • “Lithium is one of the most important elements in the human body.” -Lawrence Wilson, M.D., author of “Lithium”
  • “Lithium itself is not a drug; it’s a naturally occurring mineral salt like potassium, and is something you need for proper mental and physical health… Lithium orotate may be a safe and simple way to help beat the blues.” -Al Sears, M.D.
  • “Lithium is one of the most important elements in the human body.” -Lawrence Wilson, M.D., author of “Lithium”
  • “Lithium is a trace element which has important functions in the brain, including protecting brain cells from various toxins and reducing the ill effects of certain excitatory neurotransmitters which are harmful in large amounts.” -Alice R. Laule, M.D., author of “Lithium”
  • Lithium is the most powerful essential trace mineral ever discovered for promoting optimal functioning of the brain and central nervous system.

Why Is Lithium Important?

  • Medical doctors are now speaking out about the essential trace mineral known as lithium, promoting its incredible therapeutic benefits at low servings.
  • Lithium is an essential trace mineral. When lithium is removed from the diet of farm animals, they appear to develop numerous chronic, degenerative diseases. These include atrophy of the spleen, development of cysts and tumors, severely depressed immune systems, and decreased fertility. Additionally, the quantity of breast milk is diminished in nursing mothers with inadequate lithium stores.
  • A study from Texas analyzed 27 state counties between the years of 1978-1987. It was discovered that the incidence of suicide, homicide, rape, drug abuse, and felonious acts were about 50% lower in the 27 counties with lithium-containing drinking water. The water had lithium levels ranging from 70-170 micrograms/L. Additionally, the study found a significant reduction in drug-related arrests within the same time period and locations.
  • “In small servings (15 mg/day), lithium orotate has been shown to protect the central nervous system.” -Dietrich K. Klinghardt, M.D, Ph.D.
  • Harvard Medical School has analyzed over 30 human meta-analysis studies and has determined that lithium reduces the rate and risk of suicide attempts by 80-90% in patients with major depression, bipolar disorder, and schizoaffective disorder. In fact, the overall risk of suicides was five times less among lithium-treated subjects compared with individuals not treated with lithium.
  • In human studies among healthy populations, lithium has been shown to significantly increase brain mass in both gray and white matter.
  • Lithium augmentation appears to be a promising therapy for geriatric patients who are unresponsive to, or cannot tolerate, other standard therapies.
  • “In some cases, adjunctive lithium leads to improvement in mood very quickly, usually in 2 or 3 days.”
  • In a placebo-controlled human study, lithium reduced histamine and bronchial reactivity in airway smooth muscle, improving symptom scores. Lithium also significantly reduced the contractile effect of histamine on the tissues of the lung and trachea in guinea pigs.
  • Lithium may support the blood vessels in humans. Animals rendered lithium deficient in lab testing developed calcification of blood vessels, increasing the risk for heart concerns.
  • Lithium has been shown to reduce excessive levels of arachidonic acid in the brains of rats. “…lithium might be considered for promoting normal brain health in humans.”
  • Lithium has been discovered to produce profound improvement of immune function by increasing these white blood cell components: granulocytes, monocytes, natural killer T-cells, and immunoglobulins.
  • Multiple studies have suggested lithium’s possible role in alleviating occasional headaches.
  • Lithium also provides robust protection from toxic metal toxicity. Lithium has been shown to protect cells from aluminum, arsenic, cadmium, lead, and mercury toxicity. Animal studies has positioned lithium as having a protective effect against toxic metals.
  • Lithium has soothing effects upon the bowel. Lithium works at the core of stress-related illnesses by balancing, normalizing, and regulating stress hormones like adrenaline and noradrenaline. “Lithium plays a gastro-protective role.”

Is Lithium Safe?

  • Lithium orotate “…does not require blood tests to establish a therapeutic level as prescription forms do, nor is it toxic to the kidneys like lithium pharmaceuticals.” In addition, “…Prescription lithium is poorly absorbed by cells, the main site where it performs its functions.” -Ward Dean, M.D.
  • According to Jonathan Wright, M.D., America’s top authority on lithium orotate, a total daily intake of 30 milligrams of elemental lithium will have unnoticeable effects on serum lithium levels, with levels usually residing in a non-detectable range. Even 40 mg per day appears to be completely safe, presenting no negative side effects or signs of toxicity.
  • Dr. Wright also testifies that, “After decades of clinical research and laboratory testing of the compound on my patients, I discovered that administering lithium orotate up to 40 mg per day to be completely safe (without negative side effects or toxicity) and absolutely effective in the control of numerous mental, neurological, and physical conditions.”
  • Dr. Dean also states, “Lithium orotate has also been successfully used in alleviating discomfort from [some types of occasional] headaches… Lithium Orotate is extremely safe, with no known adverse side effects or drug interactions.”
  • “Lithium orotate is effective at uncommonly low serving sizes and causes no negative side effects.” -Dr. Hans Nieper

What’s the Best Form of Lithium?

  • Another form of lithium, called lithium orotate, is preferred because the orotate ion crosses the blood-brain barrier easily. Therefore, lithium orotate can be used in much lower servings (e.g. 5 mg) with remarkable results and no side effects. -Shaheen Lakhan, M.D., author of “Nutritional Therapies for Mental Disorders”
  • “The lithium salt of orotic acid (lithium orotate) improves the effects of lithium several-fold by increasing lithium bio-utilization.” -Ward Dean, M.D., author of “The Unique Safe Mineral with Multiple Uses”
  • Available without a prescription, lithium orotate is lithium joined with an orotate ion, rather than to a carbonate ion.
  • “Lithium orotate is a highly bioavailable form of lithium that is available as an over-the-counter dietary supplement.” -Linda Fugate, Ph.D., author of “Lithium’s Potential Role in Preventing Alzheimer’s Disease”
  • In 1973, Dr. Hans Nieper reported that approximately 90% of his migraine patients reported significant relief in the frequency and severity of their headaches. He states that he was able to produce these results by utilizing a unique mineral transporter known as orotic acid (aka, orotate), thus allowing him to administer only minute amounts of lithium to achieve maximum results.

REFERENCES

  1. Apaydin EA, et al. A systematic review of St. John’s wort for major depressive disorder. Syst Rev. 2016;5(1):148.
  2. Pratte MA, et al. An alternative treatment for anxiety: a systematic review of human trial results reported for the ayurvedic herb ashwagandha (Withania somnifera). J Altern Complement Med. 2014 Dec 1;20(12):901-908.
  3. Valerian. National Centre for Complementary and Integrative Medicine, US Department of Health and Human Services. 2016. Accessed 15 Apr 2020.
  4. Jainarinesingh J. Herbs that ensure good health and longevity. West Indian Med J. 2014 Jan;63(1):90-91.
  5. Ishaque S, et al. Rhodiola rosea for physical and mental fatigue: a systematic review. BMC Complement Altern Med. 2012;12:70.
  6. Darbinyan V, et al. Clinical trial of Rhodiola rosea L. extract SHR-5 in the treatment of mild to moderate depression. Nord J Psychiatry. 2007;61(5):343-348.
  7. Kennedy DO. B vitamins and the brain: mechanisms, dose and efficacy — a review. Nutrients. 2016 Feb;8(2):68.
  8. Penckofer S, et al. Vitamin D and depression: where is all the sunshine? Issues Ment Health Nurs. 2010 Jun;31(6):385-393.
  9. Marshall TM. Lithium as a nutrient. J American Physicians Surgeons. 2015;20(4):104-109.
  10. Bozatello P, et al. Supplementation with omega-3 fatty acids in psychiatric disorders: a review of literature data. J Clin Med. 2016 Aug;5(8):67.
  11. Cerdo T, et al. Probiotic, prebiotic, and brain development. Nutrients. 2017 Nov;9(11):1247.
  12. 5-HTP. US National Library of Medicine. Updated 16 Mar 2020. Accessed 15 Apr 2020.
  13. Edwards MK, Loprinzi PD. Experimental effects of brief, single bouts of walking and meditation on mood profile in young adults. Health Promot Perspect. 2018;8(3):171-178.
  14. Bueno VF, et al. Mindfulness meditation improves mood, quality of life, and attention in adults with attention deficit hyperactivity disorder. Biomed Res Int. 2015;2015:962857.
  15. Selhub E. Nutritional Psychiatry: Your Brain on Food. Harvard Health Publishing. Updated 26 Mar 2020. Accessed 15 Apr 2020.
  16. Stewart J, et al. Music use for mood regulation: self-awareness and conscious listening choices in young people with tendencies to depression. Front Psychol. 2019;10:1199.
  17. Ozbay F, et al. Social support and resilience to stress. Psychiatry (Edgmont). 2007 May;4(5):35-40.

 

 

 

Lithium as a Nutrient

Timothy M. Marshall, Ph.D.

ABSTRACT

In high doses, lithium acts as a drug, accompanied by potentially serious and debilitating side effects. In low doses, lithium acts as a nutrient required for B12 and folate transport and uptake, neuromodulation, and the function of many biochemical processes in both humans and animals. Studies since the 1970s have shown the ability of lithium to stimulate the proliferation of stem cells. Recent studies have described its ability to up-regulate neurotrophins such as brain-derived neurotrophic factor (BDNF) and nerve-growth factor (NGF), which are important in neuronal function, plasticity, and repair. With its newly described antioxidant and anti-inflammatory activity along with powerful neuroprotective effects, low-dose lithium therapy has largely unrealized potential to prevent or treat a wide-range of neurological disorders such as traumatic brain injury (TBI), Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis (ALS), chronic pain, mercury toxicity, depression/anxiety, alcoholism, and drug addiction.
Lithium Is an Essential Element

For most people, the word “lithium” suggests images of mental unrest, imbalance, or overt mental illness. This is because societal perception of lithium for the last 100 years has almost exclusively been defined by its use in high doses (150- 360 mg elemental Li) to treat bipolar disorder and various forms of mental illness. Lithium was first discovered as a chemical element in 1817. Its first recorded medical use was in 1871 for the treatment of mania. In 1886, a highly ionizable form of inorganic lithium (carbonate), the currently used form, was introduced to treat depression. A lithium requirement in human and animal nutrition is much less publicized, and rarely discussed in Western medicine, though it is fairly common knowledge among those involved in nutritional trace element research. It has been in the scientific database for many years. In a 2002 review, researchers looked at silicon, aluminum, arsenic, and lithium, and their effect in human health and disease. The purpose was to take all of the research to date on these “ultra-trace minerals” and determine their overall nutritional significance and impact on health, taking into account their possible toxic effects. The researchers concluded that silicon and lithium have protective roles in human nutrition, while aluminum and arsenic have notably toxic effects.1 We have known for years that animals need small amounts of lithium for reproductive health and maintenance of general health and wellness. Gerhard N. Schrauzer of the University of California at San Diego writes: In studies conducted from the 1970s to the 1990s, rats and goats maintained on low-lithium rations were shown to exhibit higher mortalities as well as reproductive and behavioral abnormalities. Lithium appears to play an especially important role during the early fetal development as evidenced by the high lithium contents of the embryo during the early gestational period…. Lithium is found in variable amounts in foods; primary food sources are grains and vegetables; in some areas, the drinking water also provides significant amounts of the element. In humans, defined lithium deficiency diseases have not (yet) been characterized, but low lithium intakes from water supplies were associated with increased rates of suicides, homicides and the arrest rates for drug use and other crimes. The biochemical mechanisms of action of lithium appear to be multifactorial…with [effects on] the functions of several enzymes, hormones and vitamins, as well as with growth and transforming factors.2 It appears that when people have deficient lithium intakes they experience poorer moods and are more easily agitated and reactive, as seen with increased rates of suicide, homicides, and violent crimes in areas with low lithium in their water supply. Lithium is also important for enhancing transport of two other critically important brain nutrients, folate and vitamin B12, into cells. The transport of these factors is inhibited in lithium deficiency and can be restored by lithium supplementation. Schrauzer concluded, Since vitamin B12 and folate also affect moodassociated parameters, the stimulation of the transport of these vitamins into brain cells by Li may be cited as yet another mechanism of the anti-depressive, moodelevating and anti-aggressive actions of Li at nutritional dosage levels.2 Schrauzer estimated that the minimum daily requirement for lithium at 1 mg per day (1,000 mcg), though I believe this is a very conservative estimate and doesn’t reflect individual differences that could necessitate larger intakes for optimal health. In 1985, the EPA estimated that dietary intake of lithium in the U.S. varied from 0.6 to 3.1 mg per day.2 People who live in the Andes of Northern Argentina have been estimated to consume between 2 to 30 mg per day, with 2 to 3 mg specifically from drinking water.3 Factors such as dietary sodium and caffeine intake increase Lithium as a Nutrient Timothy M. Marshall, Ph.D. Journal of American Physicians and Surgeons Volume 20 Number 4 Winter 2015 105 lithium excretion, and thus increase our requirement for this essential trace mineral. Along with these prevalent dietary factors, stress and excitotoxin exposure, which raise cortisol and other stress hormones, influence our physiological requirement for a variety of water-soluble nutrients (e.g. magnesium, zinc, B-vitamins), including lithium.

Lithium Induces Stem Cell Production

Stem cells, undifferentiated cells capable of differentiation into specialized cell types, have tremendous potential for promoting neuronal repair and recovery. Stem cells come from two primary sources: embryos formed during the blastocyst phase of embryological development or from adult tissue (e.g. bone marrow, blood, neural, and adipose cells). Both types are able to differentiate into various cell types comprising the skin, nervous system, bones, muscle, and other tissues.4 Studies published since the 1970s have described the ability of lithium to stimulate blood-cell formation, thus counteracting the negative side effects associated with various medications, such as carbamazepine, zidovudine, and chemotherapeutic agents. Increases in blood neutrophils and eosinophils are regularly observed, though lymphocytes and erythrocytes remain unaffected.7 This hematopoietic effect is thought to be a direct result of pluripotent stem-cell production8-10 and/or enhanced colony stimulating factor production.11, 12 In 2011, Wang and colleagues revealed that lithium greatly enhances the generation of induced pluripotent stem cells from both mouse embryonic fibroblast and human umbilical vein endothelial cells. The authors found that lithium exerts its effect epigenetically via down-regulation of LSD1, a H3K4- specific histone demethylase.13 Rutgers researchers Dong Ming Sun and Wise Young filed a patent in 2013 using a lithium salt to stimulate cord blood stem cell proliferation and growth factor production.14

Lithium Effects on Neural Tissue and Blood

In his 2009 review,15 Young cited the following biochemical effects and benefits: • Lithium up-regulates neurotrophins, including brainderived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin-3 (NT3), as well as receptors to these growth factors in the brain. • Lithium stimulates proliferation of stem cells, including bone marrow and neural stem cells in the subventricular zone, striatum, and forebrain. The stimulation of endogenous neural stem cells may explain why lithium increases brain cell density and volume in patients with bipolar disorders. • Lithium also remarkably protects neurons against glutamate, seizures, and apoptosis due to a wide variety of neurotoxins via N-methyl-D-aspartate receptor (NMDA) inhibition/modulation. • Lithium causes granulocytosis and enhances immunological activities of monocytes and lymphocytes. Young concludes, “Lithium has been reported to be beneficial in animal models of brain injury, stroke, Alzheimer’s, Huntington’s, and Parkinson’s diseases, amyotrophic lateral sclerosis (ALS), spinal cord injury, and other conditions. A recent clinical trial suggests that lithium stops the progression of ALS.”15 In 2014, Stenudd et al. demonstrated that endogenous neural stem cells restrict damage and promote repair of damaged spinal cord neurons.16 Lithium’s ability to stimulate neural stem cell production may prove to be of significant benefit in individuals recovering from spinal cord injury and neurological injuries caused by severe trauma (TBI, traumatic brain injury), dietary and environmental excitotoxins (mercury, aspartame, monosodium glutamate), and substance abuse.

Mechanism of Neuroprotective Effects

Three primary mechanisms have been identified over the last two decades for the wide-ranging neuroprotective effects of lithium on the brain and nervous system: up-regulation of the major neuroprotective protein Bcl-2, upregulation of BDNF, and inhibition of NMDA receptor-mediated excitotoxicity. In 2002, Manji et al. found that lithium up-regulates the cytoprotective protein Bcl-2 in the CNS in vivo. They state: “Strategies that increase Bcl-2 levels have demonstrated not only robust protection of neurons against diverse insults, but have also demonstrated an increase in the regeneration of mammalian CNS axons. To date, lithium remains the only medication demonstrated to markedly increase Bcl-2 levels in several brain areas; in the absence of other adequate treatments, an investigation of the potential efficacy of lithium in the long-term treatment of several neurodegenerative disorders is warranted.”17 At sub-therapeutic levels, lithium prevented glutamateinduced excitotoxicity through NMDA receptor inhibition. The neuroprotection observed was correlated with inhibition of NMDA receptor-mediated calcium influx.18 Part of lithium’s protection against glutamate-induced excitotoxicity was conferred by a primary neural growth factor, BDNF, required for neuronal function, synaptic plasticity, and repair—and therapeutic doses of lithium result in a beneficial increase of BDNF in cortical neurons.19 Lithium’s inhibition of the NMDA receptor parallels that of another essential (anxiolytic/anti-stress, anti-depressant) nutrient, magnesium—modulating and reducing the receptor hyperactivity associated with a number of disease states, including depression, anxiety, chronic pain, and sleep disorders.

Alzheimer Disease

Recent findings implicate changes in BDNF levels in the pathogenesis of Alzheimer’s disease. An early increase may reflect a compensatory repair mechanism in early neurodegeneration and could also contribute to increased degradation of β-amyloid. During the course of the disease, BDNF decreases, correlating with the severity of dementia.20 Strategies that increase BDNF levels in the brain could thus 106 Journal of American Physicians and Surgeons Volume 20 Number 4 Winter 2015 be a primary target in the prevention, slowing, and perhaps reversal of fundamental biochemical deficits and changes that drive Alzheimer’s disease. Some studies have suggested that coffee intake and exercise, both powerful inducers of BDNF release, possess cognitive-enhancing, neuroprotective properties. A coffee fruit extract was associated with a 143 percent increase in plasma BDNF levels in healthy subjects over baseline controls levels.21 Authors of a 2014 review concluded: “Coffee intake demonstrated a protective effect against cognitive decline with 6.25 fold lower risk with increased coffee intake.”22 A 2014 study of subjects with a mean age of 67 showed that exercise-increased BDNF levels correlated with improved executive function.23 These simple lifestyle factors could help reduce cognitive impairment with age, while providing immediate benefits in cognitive performance. Forlenza et al. stated that in humans, lithium treatment has been associated with humoral and structural evidence of neuroprotection, such as increased expression of anti-apoptotic genes, inhibition of cellular oxidative stress, synthesis of brain-derived neurotrophic factor (BDNF), cortical thickening, increased grey matter density, and hippocampal enlargement. In addition, lithium’s inhibition of glycogen synthase kinase-3 beta (GSK3B) may modify biological cascades involved in the pathophysiology of Alzheimer’s disease. A recent placebocontrolled clinical trial in patients with amnestic mild cognitive impairment (MCI) showed that long-term lithium treatment may actually slow the progression of cognitive and functional deficits, and also attenuate Tau hyperphosphorylation in the MCI-AD continuum. Therefore, lithium treatment may yield disease-modifying effects in Alzheimer’s disease, both by the specific modification of its pathophysiology via inhibition of overactive GSK3B, and by the unspecific provision of neurotrophic and neuroprotective support.24 In a follow-up study, Forlenza et al. state: “The putative neuroprotective effects of lithium rely on the fact that it modulates several homeostatic mechanisms involved in neurotrophic response, autophagy, oxidative stress, inflammation, and mitochondrial function.”25 In a landmark study, Nunes et al. found that a small dose (0.3 mg) of lithium administered once daily to Alzheimer’s disease patients prevented cognitive decline over a 15-month period, with significant differences seen in the treatment and control groups by the third month and progressing through the course of treatment.26 Additional studies and clinical trials will be needed to determine the most effective dose.

Anti-Inflammatory Activity

Julian Lieb described lithium’s anti-inflammatory and antiprostaglandin effects.27 Basselin et al. stated that a portion of lithium’s therapeutic activity can be explained by its ability to reduce inflammation through a reduction in brain arachidonic acid metabolism, and an increase of the anti-inflammatory metabolite and docosanoid precursor, 17-hydroxy-DHA.28 Along with lithium, docosanoids are increased by common anti-inflammatory agents such as aspirin. This is a very significant finding because all chronic diseases possess some degree of inflammation as a defining feature in their etiology and progression. Lithium, with its ability to reduce inflammation—in small, nutritional doses, devoid of the side effects commonly seen with high-dose therapy—may serve as a powerful adjunctive therapy in the treatment of a wide-range of chronic inflammatory diseases.

Antioxidant, Anti-Aging Activity

Along with elevating stress hormones, chronic stress is known to increase free-radical production. Coupled with its anti-inflammatory activity, lithium has been shown to possess antioxidant effects29,30 through the inhibition of free-radical production, while increasing the activity of endogenous antioxidant systems such as glutathione peroxidase.30 Suggesting a potential link between lithium’s neuroprotective, antioxidant effects and cognition, Vo et al. state that animal studies have shown positive results regarding the neuroprotective and antioxidant properties of lithium, while human studies indicate a potential benefit of lithium for improving cognition.29 Lithium has also been shown to be a longevity (“anti-aging”) nutrient. It’s been observed that populations who consume higher amounts of lithium in their water show reduced allcause mortality.31

Lithium and Mercury Toxicity

Lithium may benefit those with elevated mercury levels from fish consumption or dental amalgams. Symptoms of mercury toxicity include irritability, depression, anxiety, sensitivity to stress, and emotional lability, which interestingly enough are similar to the proposed symptoms of lithium insufficiency in humans. This similarity likely results from the fact that along with increasing oxidative stress, mercury increases levels of the excitatory neurotransmitter glutamate in the brain by impairing glial function, while lithium has a modulating and opposing action on glutamate (NDMA) receptors.18

Lithium, Magnesium, and Trace Elements

Both lithium and magnesium are known to possess antiinflammatory and antioxidant activities along with their specialized ability to inhibit NMDA receptor overactivation. The latter is believed to play a strong role in their antioxidant (free-radical reducing), and anti-inflammatory effects. Another essential trace mineral, zinc, which is known to exert powerful inhibitory effects on the NMDA receptor, also has antidepressant32, 33 and neuromodulatory effects, along with magnesium34 and lithium.35 Mlyniec et al. write that the deficiency of essential elements can lead to the development of depressive and/or anxiogenic Journal of American Physicians and Surgeons Volume 20 Number 4 Winter 2015 107 behavior, and that supplementation can enhance therapeutic effect of antidepressants and anxiolytics.35 To lithium and magnesium they add zinc, iron, calcium, and chromium.

Nutritional Forms of Lithium

The two most common, low-dose forms of lithium that are readily available over the counter (OTC) are the aspartate and orotate forms. In terms of chelate stability and ionizability (how easily they ionize, or generate ions in an aqueous medium), both are very stable, and are thought to be absorbed and transported largely intact (un-ionized) through the intestinal lumen, and delivered to their sites of action within the cell. In contrast, the pharmaceutical forms of lithium, carbonate and citrate, have a “loose” ionic association and readily ionize producing extracellular lithium ions, which diffuse less efficiently into the cell via sodium channels. Clinical support for the relative differences in the ionizability of different organic chelates (e.g. citrate, aspartate, glycinate, orotate, threonate, gluconate, etc.) and inorganic complexes (i.e. carbonate, oxide, and sulfate) can be readily observed in the body’s response to oral forms of magnesium. Low-to-moderate doses of readily ionizable forms of magnesium (e.g. oxide, sulfate, gluconate, and citrate) produce an osmotic effect in the intestines (exploited for this very property in clinical medicine), resulting in a laxative effect. Well-absorbed forms of magnesium (e.g. glycinate, lysinate, threonate, orotate, aspartate) are stable chelates with relatively low ionizability, and are absorbed largely intact from the intestines. These forms have high bioavailability (estimated to be greater than 60–70 percent) with virtually no intestinal side effects. In general, the more ionizable forms of minerals cause greater side effects and “biological disruption” due to their extracellularly irritating nature. For example, copper and zinc can produce nausea in relatively small doses, and poorly absorbed forms of iron (e.g. sulfate) can cause intestinal irritation, nausea, and constipation. From a firmer understanding of the various forms of lithium and other mineral nutrients, one can navigate the nutritional and pharmacological realm with greater precision and desired effect, yielding fewer unwanted side effects, and more positive clinical outcomes.

High-Dose vs. Low-Dose

Lithium Vastly different mechanisms govern high and low doses of lithium. In high doses, approximately 50–300 times greater than our dietary intake from naturally occurring lithium in food and water, lithium acts as a drug. The high doses are needed to “force” lithium into the body’s cells via a crude concentration gradient. If the extracellular concentration is high enough (at potentially toxic levels), sufficient lithium will enter via simple diffusion primarily through sodium channels to reach a therapeutic level. Like anything at a high enough level, including water and vitamins, lithium can be toxic. For low-dose lithium, the highly bioavailable orotate chelate29, 30 functions as a targeted delivery system. The stable, intact, un-ionized chelate is believed to transport the lithium efficiently through the cell membrane to its various sites of action within the cell. Stability studies of the orotate chelate conducted in the 1970s by the German physician Hans Nieper concluded that the orotate chelate was able to pass through cell membranes intact without dissociating into its component ions (Li+ and orotate-), and once inside the cell, the orotate mineral complex dissociated, releasing the lithium to its sites of action.36 Kling and Pollack found that lithium orotate was three times more effective at raising brain concentrations of the mineral than lithium carbonate. Based on the data, the authors concluded that lower doses of lithium orotate may achieve therapeutic brain lithium concentrations and relatively stable serum concentrations.37 The safety of low-dose lithium is comparable to lowdose forms of other nutrients such as zinc. In fact, lithium has a much wider therapeutic and biologically compatible (nontoxic) window than zinc. Starting with a dose at Schrauzer’s provisional RDA of 1 mg for lithium with nutritional doses up to 20 mg (representing a 20-fold difference in the “lowdose supplemental range” employed by functional medicine practitioners for many years now) is very safe with a very low incidence of side effects.38 In contrast, a 20-fold increase in the dose of zinc from the RDA of 15 mg to 300 mg would cause numerous adverse effects such as nausea, vomiting, abdominal cramps, diarrhea, headaches, weakness, irritability, immune suppression, and copper depletion.39, 40, 41 Even low-to-moderate doses (15 mg to 30 mg) of zinc, which is considered relatively nontoxic, may still promote copper depletion. Lithium is not known to cause any mineral imbalances or depletion. Concerns about the safety of lithium supplementation were raised in a letter to the editor.42 A resident physician at a university clinic evaluated a patient who reported using lithium orotate, 240 mg/d, for self-diagnosed bipolar disorder. The diagnosis was not confirmed, and the patient did not show signs of toxicity.42 Toxicity at this dose would not be expected, based on the long history of safe use of lithium throughout Europe and the U.S. for more than 40 years. Jonathan V. Wright, M.D., reports the exceptional safety of lithium (orotate) as used at the Tahoma Clinic in low, nutritionally relevant doses (5–20 mg/d).43 We need to remember the often-disregarded truism that the dose determines the poison. Water intoxication (intentional consumption of large amounts of water producing hyponatremia and subsequent organ failure) has caused many fatalities,44,45 whereas there are no reported cases of death or serious side effects in more than 40 years of lithium orotate use in Europe and the U.S. There is one case report of a woman who intentionally ingested 18 tablets of Find Serenity Now (each tablet containing 120 mg of lithium orotate, supplying 3.83 mg of elemental lithium per tablet), for a total dose of 68.9 mg. She complained of nausea with one episode of emesis, 108 Journal of American Physicians and Surgeons Volume 20 Number 4 Winter 2015 and presented with normal vital signs and a slight tremor. Symptoms resolved within three hours of observation.46

Lithium Use in Alcoholics and Drug Abusers

Schrauzer and de Vroey reported on 42 alcoholic patients undergoing treatment at a private rehabilitation clinic who were given 150 mg of lithium orotate per day (4.8 mg elemental lithium). Ten of the patients had no relapse for more than three and up to 10 years; 13 patients remained without relapse for one to three years; and the remaining 12 had relapses between 6 and 12 months. The adverse side effects noted were minor: eight patients out of the 42 total developed muscle weakness, loss of appetite, or mild apathy. The symptoms subsided when the dose was decreased from daily to four to five times weekly.47 In 1994, Schrauzer reported a placebo-controlled study of former drug users. Using a lithium-rich brewer’s yeast providing just 400 mcg (0.4 mg) per day of lithium, he found that in the lithium group, the total mood test scores increased steadily and significantly during the period of supplementation. He concluded, based on these results and the analysis of voluntary written comments of study participants, that lithium at the dosages chosen had a “mood-improving and-stabilizing effect.”37

Dietary Sources of Lithium Foods

traditionally regarded as “neurotonics,” defined as having a nourishing effect on the brain and nervous system, such as cacao, oats, seafood, seaweed, goji berries, various fruits and vegetables (depending on the soil in which they’re grown), and egg yolks are significant sources of lithium, along with other trace minerals such as iron, copper, and manganese, which are known to co-migrate along with lithium from the soil to the plant.

Toxic Challenges and Deficiences

Potential toxins from diet and environment include mercury (e.g. from large fish, vaccines, dental amalgams)48-50, aspartame (present in more than 6,000 consumer products), monosodium glutamate (e.g. from canned foods, processed foods, flavorings), Bisphenol A or BPA (e.g. from canned foods and beverages, plastics, store receipts), and other neurologically damaging excitotoxins.51-53 These neurological “assaults” are cumulative and over time can manifest in a variety of symptoms ranging from depression, anxiety, memory problems, learning difficulties, sleep disturbances, sensitivity to stress, chronic pain, and other signs of a “stressed” or compromised nervous system. Persons with any type of neurologic injury often have deficiencies in neuroprotective nutrients such as magnesium, zinc, selenium, vitamin B12, folate, and lithium. These deficiencies exacerbate the underlying conditions, while simultaneously undermining fundamental healing processes in the brain and nervous system.

Conclusion

An optimal, nutritional intake of lithium may prevent or ameliorate many neurologic and psychiatric conditions through effects on nervous system metabolism and generalized antiinflammatory and antioxidant effects. Pharmaceutical agents often mask symptoms without correcting underlying problems. Nutritional supplementation is safe—with wide-ranging neurological benefits—and should benefit overall health.
Timothy M. Marshall, Ph.D., is a holistic neurospecialist/pharmacologist and professor of chemistry and pharmacology in Tucson, Ariz. Contact: [email protected].
Disclosure: Dr. Marshall willl be marketing products containing lithium as a nutritional supplement.

References

  1. Pérez-Granados AM, Vaquero MP. Silicon, aluminium, arsenic and lithium: essentiality and human health implications. J Nutr Health Aging 2002;6:154-162. 2. Schrauzer GN. Lithium: occurrence, dietary intakes, nutritional essentiality. J Am Coll Nutr 2002;21(1):14-21. 3. Concha G, Broberg K, Grandér M, et al. High-level exposure to lithium, boron, cesium, and arsenic via drinking water in the Andes of northern Argentina. Environ Sci Technol 2010;44(17):6875-6880. doi:10.1021/ es1010384. 4. National Institutes of Health. U.S. Dept of Health and Human Services. Stem Cell Information; 2015. 5. Gallicchio VS, Hughes NK, Tse KF. Modulation of the haematopoietic toxicity associated with zidovudine in vivo with lithium carbonate. J Intern Med 1993;233:259-268. 6. Scanni A, Tomirotti M, Berra S, et al. Lithium carbonate in the treatment of drug-induced leukopenia in patients with solid tumors. Tumori 1980;66:729. 7. Boggs DR, Joyce RA. The hematopoietic effects of lithium. Semin Hematol 1983;20:129-138. 8. Gallicchio VS, Chen MG. Modulation of murine pluripotential stem cell proliferation in vivo by lithium carbonate. Blood 1980;56:1150-1152. 9. Gallicchio VS, Chen MG. Influence of lithium on proliferation of hematopoietic stem cells. Exp Hematol 1981;9:804-810. 10. Levitt LJ, Quesenberry PJ. The effect of lithium on murine hematopoiesis in a liquid culture system. N Engl J Med 1980;302:713-719. 11. Harker WG, Rothstein G, Clarkson D, Athens JW, Macfarlane JL. Enhancement of colony-stimulating activity production by lithium. Blood 1977;49:263-267. 12. Richman CM, Kinnealey A, Hoffman PC. Granulopoietic effects of lithium on human bone marrow in vitro. Exp Hematol 1981;9:449-455. 13. Wang Q, Xinxiu X, Li J, et al. Lithium, an anti-psychotic drug, greatly enhances the generation of induced pluripotent stem cells. Cell Res 2011;21:1424-1435. 14. Sun DM, Young W. Lithium stimulation of cord blood stem cell proliferation and growth factor production. Patent assigned to Rutgers, The State University of New Jersey, New Brunswick, NJ (US). US 8,852,938. 15. Young W. Review of lithium effects on brain and blood. Cell Transplant 2009;18:951-975. 16. Stenudd M, Sabelström H, Frisén J. Role of endogenous neural stem cells in spinal cord injury and repair. JAMA Neurol 2014;72:235-237. doi:10.1001/jamaneurol.2014.2927. 17. Manji HK, Moore GJ, Chen G. Lithium up-regulates the cytoprotective protein Bcl-2 in the CNS in vivo: a role for neurotrophic and neuroprotective effects in manic depressive illness. J Clin Psychiatry 2000;61(Suppl 9):82-96. 18. Hashimoto R, Hough C, Nakazawa T, Yamamoto T, Chuang DM. Lithium protection against glutamate excitotoxicity in rat cerebral cortical neurons: involvement of NMDA receptor inhibition possibly by decreasing NR2B tyrosine phosphorylation. J Neurochem 2002;80:589-597. 19. Hashimoto R, Fujimaki K, Jeong MR, et al. Neuroprotective actions of lithium. Seishin Shinkeigaku Zasshi 2003;105(1):81-86. Journal of American Physicians and Surgeons Volume 20 Number 4 Winter 2015 109 20. Laske C, Stransky E, Leyhe T, et al. Stage-dependent BDNF serum concentrations in Alzheimer’s disease. J Neural Transm 2006;113:1217-1224. 21. Reyes-Izquierdo T, Nemzer B, Shu C, et al. Modulatory effect of coffee fruit extract on plasma levels of brain-derived neurotrophic factor in healthy subjects. Br J Nutr 2013;110:420-425. 22. Al-khateeb E, Al-zayadneh E, Al-dalahmah O, et al. Relation between copper, lipid profile, and cognition in elderly Jordanians. J Alzheimer’s Dis 2014;41(1):203-211. 23. Leckie RL, Oberlin LE, Voss MW, et al. BDNF mediates improvements in executive function following a 1-year exercise intervention. Front Hum Neurosci 2014;8:985. doi:10.3389/fnhum.2014.00985. 24. Forlenza OV, de Paula VJ, Machado-Vieira R, Dinz BS, Gattaz WF. Does lithium prevent Alzheimer’s disease? Drugs Aging, 2012;29:335-342. 25. Forlenza OV, De-Paula VJ, Diniz BS. Neuroprotective effects of lithium: implications for the treatment of Alzheimer’s disease and related neurodegenerative disorders. ACS Chem Neurosci 2014;5:443–450. doi:10.1021/cn5000309. 26. Nunes MA, Viel TA, Buck HS. Microdose lithium treatment stabilized cognitive impairment in patients with Alzheimer’s disease. Curr Alzheimer Res 2013;10(1):104-107. 27. Lieb J. Defeating cancer with antidepressants. ecancer 2008;2:88. 28. Basselin M, Kim HW, Chen M. Lithium modifies brain arachidonic and docosahexaenoic metabolism in rat lipopolysaccharide model of neuroinflammation. J Lipid Res 2010;51:1049-1056. 29. Vo TM, Perry P, Ellerby M, Bohnert K. Is lithium a neuroprotective agent? Ann Clin Psychiatry 2015;27(1):49-54. 30. De Vasconcellos AP, Nieto FB, Crema LM. Chronic lithium treatment has antioxidant properties but does not prevent oxidative damage induced by chronic variate stress. Neurochem Res 2006;31:1141-1151. 31. Zarse K, Terao T, Tian J, et al. Low-dose lithium uptake promotes longevity in humans and metazoans. Eur J Nutr 2011;50:387-389. 32. Levenson CW. Zinc: the new antidepressant? Nutr Rev 2006;64(1):39-42. 33. Christine CW, Choi DW. Effect of zinc on NMDA receptor-mediated channel currents in cortical neurons. J Neurosci 1990;10(1):108-116. 34. Szewczyk B, Poleszak E, Sowa-Kućma M. Antidepressant activity of zinc and magnesium in view of the current hypotheses of antidepressant action. Pharmacol Rep 2008;60:588-589. 35. Młyniec K, Davies CL, de Agüero Sánchez IG, et al. Essential elements in depression and anxiety. Part I. Pharmacol Rep 2014;66:534-544. 36. Nieper HA. The clinical applications of lithium orotate. A two years study. Agressologie 1973;14:407-411. 37. Kling MA, Manowitz P, Pollack IW. Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate. J Pharm Pharmacol 1978;30:368-370. 38. Sartori HE. Lithium orotate in the treatment of alcoholism and related conditions. Alcohol 1986;3:97-100. 39. Higdon J. Zinc. Micronutrient Information Center, Linus Pauling Institute, Oregon State University. 40. Office of Dietary Supplements, National Institutes of Health. Zinc—Fact Sheet for Health Professionals. Reviewed Jun 5, 2013. 41. Weil A. Zinc—Supplements and Herbs. drweil.com; Jan 12, 2015. 42. Balon R. Possible dangers of a “nutritional supplement” lithium orotate. Ann Clin Psychiatry 2013;25(1):7. 43. Wright JV. Library of Food and Vitamin Cures (Nutrition & Healing). New Market Health Publishing; 2011. 44. Associated Press. Woman dies after water-drinking contest. NBCNEWS. com; Jan 13, 2007. Available at: http://www.nbcnews.com/id/16614865/ ns/us_news-life/t/woman-dies-after-water-drinking-contest/#.VU5- VPlVhHw. Accessed May 9, 2015. 45. Ballantyne C. Strange but true: drinking too much water can kill. Sci Am, Jun 21, 2007. 46. Pauzé DK, Brooks DE. Lithium toxicity from an Internet dietary supplement. J Med Toxicol 2007; 3:61-62. 47. Schrauzer GN, de Vroey E. Effects of nutritional lithium supplementation on mood: a placebo-controlled study with former drug users. Biol Trace Elem Res 1994;40:89-101. 48. Ni M, Li X, Rocha JB, Farina M, Aschner M. Glia and methylmercury neurotoxicity. J Toxicol Environ Health A, 2012;75:1091-1101. 49. Pieper I, Wehe CA, Bornhorst J, et al. Mechanisms of Hg species induced toxicity in cultured human astrocytes: genotoxicity and DNA-damage response. Metallomics 2014;6:662-671. 50. Mutter J. Is dental amalgam safe for humans? The opinion of the scientific committee of the European Commission. J Occup Med Toxicol 2011;6(1):2. 51. Blaylock RL. Lithium. In: Excitotoxins—the Taste That Kills. Health Press; 1997. 52. López-Pérez SJ, Ureña-Guerrero ME, Morales-Villagrán A. Monosodium glutamate neonatal treatment as a seizure and excitotoxic model. Brain Res 2010;1317:246-256. 53. Lee S, Suk K, Kim IK, et al. Signaling pathways of bisphenol A-induced apoptosis in hippocampal neuronal cells: role of calcium-induced reactive oxygen species, mitogen-activated protein kinases, and nuclear factor-kappaB. J Neurosci Res 2008;86:2932-2942.

 

 

 

Lithium Orotate Dosage for Depression

 

What is Lithium Orotate?

Struggling with depression and low energy? Need a quick boost of motivation? Then lithium orotate might be the answer to your problems. This dietary supplement is made from lithium, a mineral that occurs naturally in the body. People with severe depression, bipolar disorder, and schizophrenia often have a lithium deficiency. By adding this mineral to your diet, you’ll have a better mood and focus better on your daily tasks.

How Does Lithium Orotate Work?

Lithium orotate is a mood regulator that helps relieves stress, depression, and anxiety. It’s 20 times more powerful than other lithium salts, so it works in smaller amounts. This trace mineral improves overall health and boosts mental focus, without the side effects associated with prescription drugs.

Unlike other lithium salts, this mineral can pass through cell membranes intact and doesn’t break apart into ions. Thus, it’s needed in lower doses to achieve the same results as lithium carbonate. The recommended dose is one milligram to 30 milligrams per day. Lithium orotate dosage depends on the condition that is being treated. A healthy individual can benefit from taking as little as one milligram, while a depressed patient needs 20 to 30 milligrams a day, split into several doses.

The Benefits of Lithium Orotate

Due to its high bioavailability, lithium orotate is easily absorbed into the body and provides remarkable results. In the past, it was widely used for treating bi-polar and manic disorders. Today, it’s popular among those who need more energy, motivation, and mental focus.

This supplement increases the activity of chemical messengers in the brain, which helps stabilize your mood and ward off depression. Lithium orotate doesn’t cause any side effects or drug interactions as long as you stick to the recommended dose. It has zero toxicity and can be used on long term. Whether you’re depressed, anxious, or have panic attacks, this product can help.

Where to Get It

Like many other supplements on the market, the FDA may be close behind on trying to regulate them, so it’s good to get some before it’s difficult to find a reputable dealer. Absorb Health has them in capsule form at a very reasonable price. If you have any experience on it, leave a comment below!

 

 

 

 

 

Lithium Orotate Anxiety Benefits

There are many ways to deal with anxiety and depression, one of which is as easy as taking the right supplement every day. Lithium Orotate anxiety supplement is a great addition for anyone struggling with these issues. Lithium Orotate benefits most types of mood disorders

Quiet, reserved, thoughtful and deep – these are just a few words that perfectly describe people with introverted personalities. These traits are wonderful in many ways, but people who fall under the INxx personality types have higher sensitivities, making them prone to unique health problems such as anxiety, depression or other mood
disorders.

Being introverted doesn’t mean that there is nothing you can do about being prone to these mood disorders.

(The following post is a guest post from our friends over at Anabolic Health)

 

Lithium Orotate Anxiety and Mood Disorders

One of the most common supplements for mood disorders is lithium orotate. And while it has always been associated with psychiatric medication, lithium is an alkali metal that comes from the same family as sodium and potassium. Originally discovered to treat manic depression (now known as bipolar disorder), it has been used for a long time to stabilize mood and treat a wide range of mood disorders.

The specific connection between lithium and how it works for mood disorders is inconclusive. Doctors believe, however, that lithium increases the synthesis and release of the happy hormone serotonin. It also does the opposite to the stress hormone norepinephrine.

But that’s not the only effect of lithium. Aside from improving emotional balance, lithium provides many excellent benefits including the following:

  • Brain protection – regular lithium treatment has shown to have neuro-protective effects. It increases Heat Shock Proteins which promotes the disposal of abnormal proteins and refolding of misfolded proteins in the brain. It also induces a certain molecule in the brain known as Bcl-2 that protects brain cells from dying.

 

  • Heart protection – it also increases the production of VEGF or vascular endothelial growth factor, a protein that promotes cell development and neurovascular remodeling. This has been found to help people recover faster from a stroke.
  • Improves brain function – Lithium increases N-acetyl aspartate (NAA) in the brain, which is correlated with IQ scores. It has also been found to create new neurons in the hippocampus, which is the brain’s memory center
  • Increases longevity – A 2011 study found a positive correlation between life-span and levels of lithium in drinking water, with the conclusion that long term low-dose exposure to lithium may exert anti-aging capabilities.

 

Lithium Orotate Benefits vs. Other Forms of Lithium

With these positive things about lithium, you may wonder why it still has a cloudy reputation until today. This is because in very high doses, the mineral can be toxic to the body.  The body poorly absorbs pharmaceutical forms of lithium – lithium carbonate and lithium citrate – hence they’re always taken in huge doses to obtain a satisfactory effect. Individuals taking these versions have to be monitored and have their blood checked regularly to ensure that they do not reach toxic levels.

Lithium orotate anxiety treatment differs from prescription lithium. The orotate binder transports the lithium easily into the membranes of the cells, requiring a much lower dosage than prescription forms of lithium. For example, severe cases of depression may only require a dose of 150 mg of lithium orotate per day. This is far lower than 900 to 1800 mg of prescription lithium. Because intake is generally lower, there are no adverse side effects, making it safe for everyday use.

 

 

 

 

How to use low-dose lithium orotate for bipolar disorder and recurrent depression

http://www.balancingbrainchemistry.co.uk/peter-smith/109/Lithium-Orotate-for-Bipolar-and-Depression/How-to-Use-Low-dose-lithium-orotate-for-bipolar-&-depression–.html

 

In this post I show you 5 tips to make low-dose lithium orotate work more effectively so that you can use a low-dose without the side-effects and still obtain therapeutic benefits

 

Does low-dose lithium orotate work?

Unfortunately most of the research into lithium as a medicine has been conducted using lithium carbonate for the prevention of mania in bipolar type I. For this purpose lithium can be a very effective treatment however it has to be used at very high doses near the level that becomes toxic. These high doses of lithium carbonate can cause hand tremors, tinnitus, weight gain, feeling emotionally flat, thyroid problems and irreversible kidney damage.

For some people lithium carbonate becomes toxic straightaway and they have to discontinue, some people can tolerate it for many years but unfortunately eventually they suffer from progressive thyroid and kidney damage and for perhaps 25% of people with bipolar lithium is not an effective medicine at all.

The question is, is low-dose lithium orotate strong enough to work as a mood stabiliser for bipolar type I and is an effective medicine for bipolar type II and an effective treatment for chronic depression?

Well I believe that it is, I have bipolar disorder (type II with rapid cycling and mixed states) myself and I used 10 mg of lithium from lithium orotate a day as part of my wellness regime.
Why use Lithium orotate in place of lithium carbonate

Lithium has so many beneficial effects for the bipolar brain, the depressed brain and also for healthy brain’s to prevent ageing-related diseases and it would be nice to obtain these benefits but without the side-effects and low-dose lithium orotate combined with other remedies may enable us to get the brain benefits of lithium without the side-effects.

It appears that lithium orotate is absorbed into the brain more efficiently than lithium carbonate and so lower doses may still be effective and many people feel that they are but without the side-effects[i] .

It used to be a mystery as to how lithium works but we now know it exerts multiple therapeutic effects and what I propose is by understanding these effects and taking additional remedies that enhance these effects we can enhance the effectiveness of the low-dose lithium orotate and get the benefits without the side-effects.

DISCLAIMER
Although I am a great proponent of people using natural self-help therapies to improve and take control of their health do not under any circumstances discontinue any medication that you need to keep you safe. Natural remedies including low-dose lithium orotate are not as strong as pharmaceuticals and you cannot simply replace mood stabilisers including lifting carbonate with lithium orotate. I keep my own bipolar disorder completely under control using natural remedies but it took me years of study and trial and error to work out how to do this and because the natural remedies are not so strong I have to take a lot of them swallowing 25 pills with breakfast and the same with dinner.
Lithium is not a drug it’s an essential nutrient

When you think of lithium what comes to your mind, do you think of a powerful drug associated with serious mental illness, well that’s one aspect of lithium but it’s a mistake to think that the only role lithium has in health and medicine.

When animals have been fed a diet containing no lithium they suffered serious health consequences to their spleen, immune system, reproductive system and brain health; establishing that lithium is an essential nutrient required in our diet. The exact daily requirement has not yet been determined, preliminary suggestions are that the RDA for lithium should be about 1 perhaps 2 mg for the average healthy person. If you are interested in my work however then sorry to say you are probably not an average healthy person and your brain may do better with above average levels of lithium.

In nutritional medicine were not only concerned with preventing deficiencies, what we do is to use natural nutrients at elevated but still safe doses to push accentuate the effects that that nutrient house in the body. In the case of lithium primary effects are on the health brain and this leads to the question:
Why do you want to take lithium in the first place?
What are the specific health benefits, properties or effects that lithium has met you want or need help within your brain?

The health benefits of lithium:
Lithium enhances the metabolism of every neurotransmitter studied; lithium boosts serotonin, dopamine, norepinephrine, GABA and acetylcholine activity in the brain.
Lithium boosts diminished signal activity (2nd messenger signals) in depressed and bipolar depressed brains.
Lithium controls mania by dampening down excess glutamate in the manic brain.
Lithium controls mania by dampening down excess dopamine in the manic brain.
Lithium decreases inflammation in the brain
Lithium counteracts Canadian buildup in the manic brain.
Lithium boosts neuroplasticity to recover lost synapses in volume in the depressed and bipolar brain.
How to make low-dose lithium orotate more effective

Tip #1 to make low-dose lithium orotate effective

Combine inositol with lithium to increase activity in the depressed brain

Scans show in the depressed brain there is significantly reduced activity on many levels, including blood flow, metabolic energy production and more.

In contrast to neurotransmitters that carry signals from one neuron to another across the synaptic gaps that exist in synapses between neurons, signals are carried within neurons by what is called the second messenger system.

In the depressed brain there is under activity of the second messenger system and lithium counteracts underactive second messenger signal strength in the depressed brain boosting activity.

One of the main molecules used by the second messenger system is inositol and inositol has been shown to have antidepressant effects at least in some studies[ii]. Studies into the antidepressant effects of inositol have been limited but this is common with natural remedies and the results have been inconsistent. Inconsistent results should not be interpreted as meaning that a substance does not have therapeutic effects for some individuals, it could be that some people reduced inositol second messenger activity is not involved in depression and therefore supplementing inositol would have no effects, however for others it could be very therapeutic.

CAUTION
In bipolar mania there is increased inositol second messenger activity and it is believed that one of the ways that lithium counteracts mania is by dampening down inositol activity in the neurons. So during manic phases you would never take inositol and you should be cautious using inositol as an antidepressant supplement if you have bipolar depression because it could flip you up into mania.

In my clinic I routinely simultaneously combine remedies that are antidepressant and antimanic or mood stabilising at the same time; this so-called combination therapy can be an effective way to manage bipolar depression. With regard to lithium and inositol however they appear to have such contradictory and opposing effects that I do not recommend supplementing inositol with bipolar disorder except perhaps as an emergency during periods of suicidal depression.

People with depression may be concerned that lithium could further suppress their second messenger system because in the bipolar brain it reduces inositol but the fact that lithium can have an antidepressant effect for chronic unipolar depression suggests that it works differently in the unipolar as opposed to bipolar depressed brain.

Inositol may also have therapeutic benefits for improving insulin sensitivity and treating polycystic ovarian syndrome so if you have PCOS/insulin sensitivity/type II diabetes and depression you should definitely try inositol. This doesn’t mean to say that inositol is only potentially useful for women.

The bottom line is that inositol is regarded as a very safe substance up to 20 g and so you can conduct a personal experiment to see that has therapeutic effects for you.
Tip #2 to make low-dose lithium orotate effective

Lithium dampens down excess glutamate in bipolar mania

One of the therapeutic effects of lithium is that it increases the rate of clearance of glutamate from the synapses. During periods of bipolar mania the excitatory neurotransmitter glutamate builds up inside the synapses causing excessive firing or activity within the brain. This produces the classic speeded up thinking, increased energy and activity characteristics of mania/hypomania.

If this is the effect you are looking for there are additional remedies you can use to increase the clearance rate of glutamate from your synapses including:

Zinc at high doses of doses of 40-60 mg. When I first began to take control of my hypomania’s I would sometimes take doses as high as 90 mg for one or two days to heavily sedate glutamate activity in my brain. It would knock me out and make me sleep (and sleeping in a totally dark room is one of the best treatments for mania) but 90 mg a day will become toxic if taken long-term; even doses as high as 60 mg can compete with iron and copper resulting in these minerals becoming deficient and so you have to protect these. Iron is actually needed to manufacture dopamine and so if you became iron deficient they could actually create depression.

NAC cysteine
At moderate doses evenly distributed such as 600 mg twice a day NAC cysteine can help to counteract glutamate buildup in the synapses. Higher doses however of say 1200 mg taken in a single dose can have a dopaminergic antidepressant effect which can be great at times of depression but must be avoided when the goal is to control mania/hypomania.

Unlike any other amino acid remedy NAC cysteine appears to lose its effectiveness if taken for six months or so continuously, a simple strategy to avoid this habituation is to omit taking it one day per week.

Magnesium is another remedy that assists clearance of glutamate from the synapses that you can supplement along with lithium to enhance its effectiveness. 800 mg divided between two meals would be the standard dose however if you have kidney insufficiency perhaps from taking lithium carbonate ironically then I would recommend a lower dose of 400 mg for safe long-term use. Magnesium comes in several forms, which one you choose will depend upon other factors and health goals.

Riboflavin, I read in a scientific paper that riboflavin has anti-glutamate effects however I haven’t had the opportunity to make any clinical observations how effective or not riboflavin may be.

Vigourous exercise counteracts elevated glutamate activity, additional strategies I use myself are supplementing glycine and taurine.
Tip #3 to make low-dose lithium orotate effective

Lithium reduces inflammation in the brain, to enhance its effectiveness eliminate every source of unnecessary inflammation in your body and brain

There are numerous sources of inflammation which I talk about in other posts however common and significant ones include:
Stress Induced Inflammation

Overactive stress responses in the body increases inflammation in the brain. What matters is how active the stress physiology in your body is, rather than how much stress you have in your life. Brain scans have shown that in people with depression and bipolar disorder there is enlargement and overactivity in what is called the HPA axis. In response to stress or the perception of threat the hypothalamus signals to the pituitary to signal to the adrenal glands to discharge the hormone cortisol and when cortisol levels are chronically high it ramps up inflammation in the brain.

An overactive HPA axis may be genetically preprogrammed or acquired as an adaptation to prolonged stress exposure particularly in the early years. The most efficient and direct I use for this issue is growing and developing the off switch to the HPA axis by performing a course of deep relaxation brain training. I have a free MP3 recording to guide you through this technique, to obtain a copy of this simply email me at [email protected] asking for the deep relaxation brain training MP3.

Additional strategies to reduce stress induced inflammation include psychotherapy to remodel traumatic memories and experiences that repeatedly trigger the HPA axis, meditation has also been shown to reduce chronic stress (I teach meditation classes specifically designed for mental health problems online, see my site for details, another technique is vagus nerve stimulation.
Dietary Induced Inflammation

A diet containing excessive amounts of omega 6 oil ramps up inflammation in the body.

Lithium counteracts imbalanced fat metabolism in the bipolar brain

Another discovery is that people with bipolar mismanage specific fats, bipolar brain is release an excessive amount of an omega-6 fat called arachidonic acid that promotes inflammation, furthermore bipolar brains have poor metabolism of omega-3 oils EPA and DHA. When omega-3 oils are underrepresented and arachidonic acid is overrepresented the result is increased inflammation. And a deficiency (real or relative to arachidonic acid) of the omega-3 fat called DHA which is anti-inflammatory[iii].

Our body makes some arachidonic acid from the omega-6 oil (linoleic acid) found in nuts and most seed oils but we can also consume a lot of arachidonic acid directly in animal foods especially red meats and pork. Our body makes some  DHA from the oil found in a few vegetarian sources including linseeds, hemp and Chia seeds but unfortunately we only convert about 1% these vegetarian omega-3s into DHA and this is not enough to obtain the therapeutic levels needed by the bipolar brain.

A diet containing a lot of arachidonic acid (duck, chicken, eggs) and only a little DHA (fish and fish oils) are giving the lithium they take a huge obstacle to overcome and may not obtain satisfactory results from low-dose lithium;
The solution is to reduce your omega six intake by avoiding omega six vegetable oils such corn, rapeseed, sunflower seed oils et cetera, a plant-based or reduced meet diet also significantly reduces omega six intake and additionally has other anti-inflammatory effects.

Over several years of experimentation I became convinced that I could make my low-dose lithium supplements work better by altering the ratio of omega 6 to omega-3 in my diet.  I would cut down on foods high in omega 6 including nuts and seeds, stopped eating red meat and cut down on white meat and eggs and increased my consumption of omega-3 fish oils;  basically I ate a more plant-protein based diet low on omega 6 containing nuts and rich in fish oils.  When I was on this diet I felt that even a microbe dose of 0.5-1 mg would have a healthy effect on my bipolar brain, it wasn’t quite mood stabilising nor did I notice it improving my neuroplasticity however it was certainly capable of correcting my disturbed bipolar sleep cycles.

To me it felt like the omega-3 oils were helping the lithium to work and I cut down on omega-6 oils because  they compete with omega-3’s, I was close but it’s the other way around it’s the lithium that is correcting an oil imbalance in the bipolar brain and what I was doing was correcting the oil imbalance as much as I could buy the oils I ate so that even a very low dose of lithium was now capable of doing the rest so to speak.  I believe that high doses of lithium carbonate used in psychiatric medicine could probably be reduced significantly for anyone prepared to eat a healthy diet low in arachidonic acid and high in omega-3.

Spikes in insulin ramp up inflammation, we get surges in insulin when we consume carbohydrates with a high GI that quickly convert into sugar.
We also get a search in insulin when we consume animal proteins without consuming any carbohydrates at the same time. This may seem counterintuitive but consumption of the small matter low GI carbohydrate at the same time as animal protein produces less insulin than if we eat protein without carbohydrates; this is the reason I do not recommend the ketogenic diet.

Brightly coloured plant foods rich in polyphenols and specifically flavonoids have anti-inflammatory and antidepressant effects so to reduce inflammation and improve the health of the brain consume vast quantities polyphenols and flavonoids rich foods together with supplementing lithium orotate.

If you have SIBO however (Small intestines bacterial overgrowth) do not consume huge amounts of plant foods until you have fixed this problem. I have been developing treatments for SIBO and IBS since late 1980s, if you’d like more information or to book an appointment contact me by email:
[email protected]

Anti-Inflammation Supplements
There are numerous anti-inflammation supplements, such things as curcumin from turmeric and skullcap. There are too many to discuss in this article and actually too many to swallow them all. When I design a prescription for a client I put together a stack of remedies that are not only anti-inflammatory that have some other common therapeutic effects, for example I may combine remedies that are anti-inflammatory with dopaminergic effects or anti-inflammatory with serotonergic effects et cetera.
Tip #4 to make a low-dose lithium orotate effective

Take 3 g of vitamins C to counteract the buildup of vanadium

Vanadium is a trace element that we naturally ingesting our diet, vanadium levels buildup in the blood and brains of people with bipolar disorder and this produces toxic oxidative stress. One of the effect of lithium is to counteract toxic vanadium effects, however vitamins C has been shown to effectively flush out and reduce vanadium levels and improve bipolar symptoms, specifically shortening the length of manic episodes[iv][v].

CAUTION
Large doses of vitamins C can affect insulin levels, diabetic treatments and blood glucose tests.
Tip #5 to make a low-dose lithium orotate more effective
Boost Neuroplasticity

Scans have shown that in depressed and bipolar brains there is a loss of synaptic connections and volume in critical structures that control mood and emotional processing including the hippocampus, cortex and insular. Lithium boosts neuroplasticity to recover lost synaptic connections and volume, there are numerous other things we can do to enhance neuroplasticity including:

  • Again a high flavonoids diet.
  • Not just what we eat but how we eat, specifically the timing of how we eat can affect neuroplasticity significantly. Practice intermittent fasting daily for at least 12 hours overnight i.e. if you have breakfast at 8 AM you must finish dinner at 8 PM.
  • It’s also critically important to not eat for at least 2 ½ hours before going to sleep because once you start producing melatonin you (the sleep hormone) it blocks insulin effectively making us insulin resistant overnight; so you have to leave a couple of hours after eating for insulin to clear out and reduce glucose levels from your evening meal before the melatonin/insulin resistance effect kicks in.
  • Aerobic physical exercise boosts neuroplasticity/BDNF but even very short bursts high intensity interval training (HIIT exercise) has significantly stronger neuroplasticity boosting effects.
  • There are numerous natural remedies that boost neuroplasticity/inflammation. I’ve been developing treatment programs to boost neuroplasticity/BDNF since 2012.
  • Meditation brain training boosts neuroplasticity and rose brain volume. We now know the more intense and activity in the brain them or neuroplastic change is stimulated, so I teach a style of meditation that involves achieving a highly focused concentrated state, the goal is to give specific parts of the brain and intensive workout in the same way that we give specific muscles a workout when we do strength training in the gym. I think of meditation brain gym.

For more information about my online meditation classes specifically designed for mental health problems click here

Summary
Lithium orotate is better absorbed into the brain and can therefore be taken at lower doses compared to lithium carbonate and at these lower doses it does not produce any or at least any serious side effects. We can enhance the effectiveness of the low dose by considering the properties or effects that lithium has in the brain and then combining additional remedies, diets and other measures to enhance those effects and therefore extract the maximum therapeutic benefits from the low dose of lithium.

 

[i] J Pharm Pharmacol. 1978 Jun;30(6):368-70. Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate. Kling MA, Manowitz P, Pollack IW. PMID:26768

[ii] Double-blind, controlled trial of inositol treatment of depression.
Levine PMID: 7726322 DOI: 10.1176/ajp.152.5.792

[iii] doi: 10.1194/jlr.M002469

[iv] Vanadium and manic depressive psychosis.
Naylor  PMID: 6443582

[v] Naylor GJ, Smith AH. Vanadium: a possible aetiological factor in manic depressive illness. Psychol Med. 1981;11:249–256. [PubMed] [Google Scholar]

 

 

 

 

 

 

 

Lithium is an alkali metal, naturally present in trace amounts in plant foods that are grown in lithium-rich soil.

It plays a role in the proper function of several enzymes, hormones, vitamins, growth factors, as well as the immune and nervous systems.

HEALTH BENEFITS

NEUROPROTECTIVE

Long-term lithium treatment reduces glutamate-induced excitotoxicity mediated by N-methyl-D-aspartate (NMDA) receptors. This effect was due to lithium’s ability to inhibit the influx of calcium, which mediates NMDA receptor activity [3].

Therefore, it can help mood disorders, Alzheimer’s, diabetes, cancer, and inflammatory and autoimmune diseases [3].

Long-term treatment of cultured neurons with lithium induces BDNF [4].

BDNF is a major neurotrophin essential for cognitive development, synaptic plasticity, and neuronal survival with anti-depressants and anti-anxiety effects. [4].

This is likely a result of the inhibition of GSK-3 [4].

Lithium also increases Nerve Growth Factor (NGF) and Glial-Derived Neurotrophic Factor (GDNF) in the hippocampus, frontal cortex, occipital cortex, and striatum [6].

NGF and GDNF help increase neuronal survival and plasticity (the ability to regenerate and form new connections) of dopaminergic, cholinergic, and serotonergic neurons in the central nervous system.

CANCER & APOPTOSIS (CELL DEATH)

Lithium helps prvent healthy cells in our body from becoming abnormal (cancer) cells [4, 5].

BRAIN AND HEART

Lithium treatment increases the production of VEGF, which promotes cell growth and remodeling of the blood vessels after stroke [4].

By increasing VEGF, lithium treatment can help people recover more quickly from a stroke or a heart attack [4].

The likely mechanism is by inhibiting GSK-3 [4].

AUTOPHAGY

Autophagy or “cellular self-eating” is when the cells degrade and recycle cellular components to reuse the raw materials [4].

It is considered anti-aging, cancer-preventing, and important for neuronal function and survival [7, 8].

Lithium can induce autophagy by depleting inositol independently of mTOR inhibition (which typically induces autophagy) [4].

Because lithium induces autophagy, it may be particularly helpful for neurodegenerative disorders – Alzheimer’s, Parkinson’s, ALS, and Huntington’s because these disorders are, in part, characterized by the accumulation of, misfolded disease-causing proteins [4].

COGNITIVE FUNCTION

Lithium was found to stimulate progenitor and stem cells in cultured brain hippocampal neurons (neurons from the memory center). In addition, lithium prevents the loss of proliferation induced by glutamate or cortisol (glucocorticoids). Long-term lithium treatment promotes the conversion of these progenitor cells into neurons [4].

In addition, chronic lithium treatment not only enhanced neurogenesis in the hippocampus (memory center) of normal mice but also restored neurogenesis in the brain in an animal model of Down syndrome [4].

It also increases neurogenesis in the subventricular zone, the only other place except for the hippocampus (memory center) that it’s been found to occur, causing a sustained increase in gray matter volume in patients [9].

Lithium increases N-acetyl aspartate (NAA), which may be a marker of creativity and is correlated with IQ scores [10, 11].

One probable effect is more efficient communication between two sides of the brain, which enhances intellectual performance. [11].

Chronic lithium treatment increases long-term potentiation (LTP) in neurons of the hippocampus, which makes the nerve cells more efficient, and thus helps with learning and memory [12].

MOOD

In animals, lithium consistently decreased exploratory activity and aggression. [13].

Lithium is known to have a calming and mood-stabilizing effect in people as well and is used to treat depression, bipolar disorder, and schizophrenia.

Lithium carbonate is the drug of choice for control of manic-depressive illness, reducing manic attacks [14, 15, 16].

It was also shown to be effective for aggressive behavior in people with attention-deficit hyperactivity disorder (ADHD) [17].

Lithium increases CCK in the brain and this is part of the mechanism by which lithium prevents mania in bipolar.

DEPRESSION

Lithium is one of the best-studied strategies for treatment-resistant depression [18].

Lithium increases serotonin 5-HT1A postsynaptic sensitivity, which is in part responsible for its antidepressant activity. [19].

Lithium also elevates BDNF, which combats depression.

Lithium ameliorates depression in animals, in part, by increasing neural stem cells.

HUNTINGTON’S DISEASE

Lithium prevented nerve cell death in animal models of Huntington’s disease [20, 21].

Lithium decreases excessive NMDA receptor function, which could potentially counteract increased activation of NMDA receptors that occurs in the brain of patients with Huntington’s disease [22].

INSULIN RESISTANCE

Lithium enhances insulin-stimulated glucose transport and glycogen synthesis in insulin-resistant muscle in rats [23].

These effects are dependent on p38 MAPK [23].

It also decreases insulin release [24].

Administration of lithium significantly increased glucose transport into muscle cells in response to insulin by 2.5 fold, and also increased insulin responsiveness [R].

AUTOIMMUNITY AND INFLAMMATION

Lithium has potent immune-boosting effects [25, 26].

By inhibiting GSK-3, lithium is beneficial in animal models of autoimmune conditions. [27].

Lithium suppresses Th1 cells and interferon gamma (but not Th17 cells) [27].

Lithium has anti-inflammatory effects by decreasing the production of IL-1β and TNF-α and increasing the production of IL-2, TGF, IL-1RA, and IL-10 [28, 29].

However, studies indicate that under certain experimental conditions, lithium also has pro-inflammatory effects by increasing the production of IL-4, IL-6, and TNF-α [30].

Lithium increases the production of IgG and IgM antibodies [31].

Lithium decreases the production and activity of prostaglandins, thus preventing its negative effect on the immune system [32].

Lithium decreased the frequency and duration of recurrent labial and genital herpes infections and reduced the occurrence of common colds [33, 34].

BONE HEALTH

A study (prospective cohort) assessed bone mineral density at the hip and lumbar spine in 75 lithium-treated outpatients and 75 normal subjects matched for age, sex, and body mass index. The study found a lower bone turnover state in those receiving lithium. The mean bone density in lithium-treated patients was 4.5% higher at the spine, 5.3% higher at the femoral neck, and 7.5% higher at the trochanter [35].

Lithium is associated with a decrease in the risk of bone fractures, and an increase in bone formation [36, 37, 38].

CIRCADIAN RHYTHM

Lithium is the drug of choice for treating patients suffering from bipolar disorder, which is characterized by the presence of mania and depression.

One mechanism by which lithium can help bipolar disorder is by lengthening the circadian rhythm. People with bipolar disorder tend to have a shorter circadian rhythm than those without bipolar.

It helps entrain our circadian rhythm more quickly in response to light and darkness.

MITOCHONDRIAL FUNCTION

Lithium treatment in worms increased lifespan and improved markers of health, including mitochondrial energy output [39].

Lithium may improve mitochondrial function by increasing the turnover of dysfunctional mitochondria [39].

Also, lithium inhibits mir-34a, which in turn inhibits NAMPT, the enzyme that makes NAD+ [4].

Therefore, lithium probably increases NAD+.

SUICIDE

Two studies found a positive correlation between rates of suicide and lithium levels in drinking water in men [40, 41]. However, another study found no significant difference in lithium levels in drinking water and rates of suicide [42].

TOURETTE’S SYNDROME

Tourette’s syndrome is a neurological disorder, characterized by involuntary muscle movements and uncontrollable vocal sounds.

In a small study involving 3 patients, lithium had a better outcome than haloperidol, a commonly prescribed drug for Tourette’s. Patients who were taking lithium experienced a significant decrease in the number of tics and involuntary vocal sounds. Patients experienced no side effects and were symptom-free months later [43].

TARDIVE DYSKINESIA

Tardive dyskinesia is a neurological disorder characterized by involuntary, sudden, and jerky movements of the face and/or body, caused by the long-term use of antipsychotic drugs [44].

Clinical studies have shown that lithium significantly reduced the severity of tardive dyskinesia [45, 46, 47].

It decreased agitation and aggression and improved involuntary movements [46, 47].

However, 2 large studies failed to report the consistent effects of lithium on tardive dyskinesia [48].

OBSESSIVE-COMPULSIVE BEHAVIOURS

Obsessive-compulsive disorder (OCD) is a mental disorder characterized by obsessive thoughts and behaviours [49].

Lithium supplementation is associated with a decrease in symptoms of OCD that are resistant to standard therapy [50].

Compulsive and pathological gamblers also had a good response to lithium supplementation, possibly by regulating dopamine imbalances in the brain [51].

HEADACHES

Lithium may reduce the severity of both chronic and episodic cluster headaches [52].

Lithium carbonate given before sleep helped with “alarm clock headache” (a headache that affects the elderly, waking them from sleep at the same time of night) [53, 54, 54].

ANOREXIA NERVOSA

Patients suffering from anorexia nervosa for many years were treated successfully with lithium carbonate [55, 56].

One patient gained 12 kg and the other 9 kg within 6 weeks, and the weight gain was maintained for a year with lithium therapy [55].

ALCOHOLISM

Lithium orotate is useful in the treatment of alcoholism.

In a study of 42 alcoholic patients, lithium was safely tolerated, with minor side effects, such as muscle weakness, loss of appetite, or mild apathy [57].

Lithium carbonate promotes abstinence from alcohol, diminishes subjective symptoms of withdrawal, and delays the time to first drink [58, 59].

Patients treated with lithium were much less likely to be re-hospitalized for alcoholism rehabilitation during the 18-month followup [60].

SEIZURES

The effect of lithium on seizure disorders is still controversial [61].

Some epileptic patients show a statistically significant decrease in seizure frequency as well as improved behaviour when treated with lithium [62].

However, a few epileptic patients experienced an increased number of seizures while on lithium [63, 64, 65]

MENIERE’S DISEASE

Meniere’s disease is a disorder of the ear that causes severe dizziness, ringing in the ears, hearing loss, and a feeling of fullness in the ear.

Seventy percent of patients with Meniere’s disease experienced less frequent and severe attacks when on lithium treatment [66].

IS IT DIFFERENT THAN THE “NATURAL” FORMS?

There’s a lot of misinformation about lithium. A lot of mainstream sources (WebMD, for instance) seem to suggest that lithium prescribed as a treatment for depression or bipolar disorder (as carbonate or chloride salts and in higher doses) works differently than over-the-counter lithium orotate.

All the research I’ve seen talks about the ion lithium, which would make the salt type of lithium not that relevant except for how bioavailable it is and how capable it is in crossing the blood-brain barrier (BBB).

Some people say that the over-the-counter version – lithium orotate – passes the brain barrier much more efficiently than the other versions.

Even assuming the possibility of some differences in dosage, studies about one form of lithium can very likely be generalized to others. In this post, we bring down studies on any form of lithium, but if you are not taking the drug with the consent of a doctor, then you should not take more than a few mg of lithium orotate a day.

JOE’S EXPERIENCE

The usual lithium orotate dosage taken is 5 mg, but I decided to take 15 mg to see what would happen. I can say that there’s definitely a subtle cognitive effect. It’s definitely got an anti-depressant and anti-anxiety effect, and it seemed to lengthen the period of my circadian rhythm, as I started to feel tired later on.

On the negative side, it made me more zoned out. It also made me feel less attached to everything. The fact that I felt acute effects at 15 mg suggests me that lithium orotate passes the brain barrier efficiently, perhaps even more so, since a much higher dosage of lithium carbonate is standardly used.

Anyway, I’m glad I did the experiment so that I now know lithium orotate is definitely having an effect and I can use it in my coaching practice.

This suggests that at least some of the benefits of other lithium salts prescribed by doctors can be achieved through the orotate version commonly sold.

Side Effects of Lithium (at high doses)

Lithium has numerous side effects and can be toxic at high doses. These symptoms are generally not relevant to lithium orotate when taken at suggested dosages (5mg).

The severity of symptoms is generally proportional to the degree of elevation of blood lithium levels [70].

Most Common

The most common side effects of lithium therapy include [71]:

  • Headaches
  • Lethargy and fatigue – this may be a result of a significant reduction in orexin-producing cells and through reducing thyroid function
  • Drowsiness
  • Hand tremors
  • Muscle weakness
  • Nausea/vomiting
  • Diarrhoea

SYMPTOMS OF MODERATE TOXICITY

Moderate toxicity (serum lithium concentration = 2.0 to 2.5 mmol/L) is characterized by [70]:

  • Confusion
  • Dysarthria (speech motor problem)
  • Nystagmus (eye twitch)
  • Ataxia
  • Muscle twitches
  • ECG changes (flat or inverted T waves)

SYMPTOMS OF SEVERE TOXICITY

Symptoms of severe toxicity (serum lithium concentration> 2.5 mmol/L) include [70]:

  • Impaired consciousness
  • Seizures
  • Syncope
  • Kidney insufficiency
  • Coma and death

Lower Thyroid Function

Lithium decreases production and release of thyroid hormones, thus hypothyroidism is very prevalent among patients on lithium therapy [72, 73, 74, 75].

Studies reported that goiter (enlargement of the thyroid gland) occurred in 50 to 60% of patients treated with lithium [76, 77, 78, 79].

Hyperthyroidism occurs rarely, and it is characterized by transient and painless inflammation of the thyroid gland (thyroiditis), due to a possible toxic effect of lithium on the thyroid gland [80, 81, 82].

Lithium induces thyroid autoimmunity by increasing B cell activity and decreasing ratios of suppressor to cytotoxic T cells [83].

As a result, 20% of lithium-treated patients have thyroid auto-antibodies.

It may also be useful in combination with radioactive iodine in the treatment of thyroid cancer [84].

OTHER NEGATIVE EFFECTS

Lithium is a competitive inhibitor of magnesium, which is part of its mechanism of action [4].

Lithium may increase inflammation in the intestines- IL-8 and Nf-kB. If you have colitis or Crohn’s, I would not take this. Colitis is caused in part by IL-8 and this increases IL-8 [85, 86].

SPECIAL PRECAUTIONS

Pregnancy and breastfeeding: Lithium can be toxic to a developing baby and increase the risk of birth defects. It can enter breast milk and cause side effects in a nursing infant.

Heart disease: Lithium should be carefully used in patients with pre-existing heart disease because it may cause irregular heart rhythms.

Kidney disease: Lithium removal from the body by the kidneys is decreased in patients with kidney disease, and the risk of lithium intoxication increases considerably in this setting.

Thyroid disease: Lithium may make thyroid problems worse.

DRUG INTERACTIONS

Antidepressant drugs (such as fluoxetine, sertraline, amitriptyline, clomipramine, imipramine), and lithium increase serotonin. Taking lithium with these medications could cause serious side effects such as heart problems, shivering, and anxiety [87, 88].

In patients treated with both lithium and an antipsychotic (haloperidol, thioridazine, chlorpromazine, clozapine, and risperidone), toxicity to the brain ranges from extrapyramidal symptoms (continuous muscle spasms or jerky movements) to neuroleptic malignant syndrome [89, 90, 91, 92].

Taking lithium along with anticonvulsant medications used to prevent seizures, such as phenobarbital, valproic acid, and carbamazepine may increase the risk of toxic effects from these drugs [93].

Medications for high blood pressure (ACE inhibitors – lisinopril, captopril, and enalapril; and calcium channel blockers – nifedipine, diltiazem, and verapamil) can increase lithium levels in the body, thus increasing its side effects [94, 95, 96, 97].

Diuretics, like water pills, and hydrochlorothiazide, chlorothiazide, and furosemide increase blood lithium concentrations by reducing lithium removal by the kidneys [98, 99].

Non-Steroidal Anti-inflammatory Drugs (ibuprofen, naproxen, and diclofenac) decrease lithium removal by the kidneys and thus increase blood lithium concentrations [100, 101, 102].

Taking lithium along with muscle relaxants (pancuronium, succinylcholine) might prolong muscle relaxation [103, 104].

Taking lithium along with dextromethorphan (Robitussin DM®), meperidine (Demerol®), or tramadol (Ultram®) may increase serotonin in the brain, and cause serious side effects including heart problems, shivering, and anxiety [93].

Acetazolamide, theophylline, and sodium bicarbonate can lower blood lithium concentrations by increasing lithium excretion in urine.

Dietary Sources & Dosing of Lithium

Primary dietary sources of lithium are grains and vegetables, which may contribute from 66% to more than 90% of the total lithium intake [105].

Cacao, oats, seafood (shrimp, lobster, oysters, and scallops), seaweed, beef liver, goji berries, various fruits and vegetables (depending on the soil in which they are grown), and egg yolks are significant sources of lithium.

LITHIUM DEFICIENCY

Lithium deficiency caused by low dietary intakes, or due to certain diseases (kidney disease, especially in dialysis patients) is unlikely to happen in humans.

If a deficiency occurs, symptoms are mild and manifest primarily as behavioral problems [105].

DOSING

If you’re completely healthy, I recommend 1 to 2 mg a day in the long term. There is an association with low doses of lithium (1 to 2 mg) and longevity [106].

However, I wouldn’t expect to feel anything at that dosage. I’ve been taking 1 mg for quite a few months, with no noticeable effect. I’ve recently upped it to 5 mg.

COMMENTS

  1. CSue August 7, 2018at 8:35 am

We need to know how those effects relate to dosage. Is 5mg of litium orotate going to cause hypothyroidism and gut inflammation and dehydration? Or only large doses used for psychiatric diseases? I suspect studies have only been done with the higher doses.

  1. Aaron Solt April 6, 2018at 6:18 pm

Lithium orotate is not natural. Lithium carbonate is. 5 mg of lithium in 120 mg of lithium orotate has as much lithium (5mg) as 50 mg of lithium carbonate. Five pills has as much lithium as 250 mg of lithium carbonate.

The reason the carbonate is prescription only is because it was fda tested. The orotate is otc because it was not tested in rats. Prorate caused rat kidneys to fail, and speeds up cancer growth. Lithium aspartate may be safer, but you have to take pills one at a time or it will tingle your nerves. Lithium carbonate is the healthiest. The high doses are for bipolar people. No one says you must go high.

Also, orotate just provides a negative charge and separates from lithium in the intestine, having no effect on brain transport. Carbonate is like the carbon dioxide bubbles in soda.

I’ve taken many university chemistry classes. Tons of websites about lithium orotate are written by bloggers and well-being practitioners who know nothing about chemistry and just repeat what they read on other such sites.

What about the aspartate form of lithium? Does that make it to the brain when taken orally and cross the BBB or is it also broken down by the digestive system?

  1. Emmy March 27, 2018at 3:15 am

By treating – Methylation problems and the micro biome , lithium was stopped for bi polar. It goes much better, no more depression or mania but still anxiety and panic attacks. We keep on struggling.

  1. OrganisedPauper March 26, 2018at 6:12 am

There has to be a huge difference between the prescribed use of lithium carbonate and over the counter lithium orotate. The ‘therapeutic’ dose for me of Li carbonate, for Bipolar Disorder, was 1200mg. I ended up with swollen legs, diabetes insipidus, extreme startle reflex, and behavioural problems that weren’t part of my disorder. Thankfully all were reversed when I came off lithium, except the startle reflex. All the listed side effects for lithium seem to be associated prescribed Li carbonate, but the dosage is huge compared to Li orotate.

  1. Murray February 27, 2018at 9:29 am

In mentioning the negatives (hypothyroid) it would be helpful to have some information on dosage. I checked you ref links and several other papers – no mention of dose. All reference seem to concern bipolar treatment so dosage is probably very high. Is there any known effect at low dose?

  1. K Mac February 5, 2018at 12:47 am

Hello there! Your cat’s vet could have recommended it for a hyperthyroid. It seems to helping with quite a few autoimmune diseases. I think because it is filling an important defeciency that humans and animals share because of the depletion of minerals
in our soils.

I’ve been taking it personally and for depression and trying to figure out my dosage. I started at 25 mg lithium
= 5 x 120 mg of lithium orotate. I was feeling great
but ran out and didn’t realize what is was doing for me at the time.
My cat has a hyperthyroid and have been researching to see if lithium orotate will help her.

Good luck!

  1. Erica January 23, 2018at 4:38 am

Can anyone advise why my vet has prescribed 5 mg Lithium twice a day for my cat after saying she has a form of Leukemia

  1. Janice January 19, 2018at 5:50 am

It is all completely useless and just pure marketing without added value. Unless Li blood level values are given with other parameters such as Thyroid hormone levels. Only by laboratory testing you can see what values you have and what Li levels you need to get to get desired effect as well monitoring other impacted parameters to see that it is not impacting something in undesired way.

  1. Tooter November 23, 2017at 12:09 pm

maybe this? >>> https://www.ncbi.nlm.nih.gov/pubmed/8403198

  1. Tooter November 23, 2017at 12:03 pm

anger management course…

  1. Tooter November 23, 2017at 12:00 pm

those symptoms actually sound kind of fun…

  1. Robert Hafemeyer November 14, 2017at 10:31 pm

Lithium chloride has been shown to increase expression of PPAR gamma. Agonism at PPAR gamma (induced by some other ligand such as BCFAs) is then associated with increased lipolysis. If you are worried about low cAMP, take something like fucoxanthin, caffeine or pentoxifylline you should see increased lipolysis. (Note that with caffeine and pentoxifylline you’d likely see increased lithium excretion)
Also, in this article, Joe talks about MAPK being activated by lithium. MAPK activation is associated with increased lipolysis.
https://www.selfdecode.com/gene/pparg/#all-ways-to-increase-gene
https://www.ncbi.nlm.nih.gov/pubmed/23527032
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2633930/

  1. Michael November 13, 2017at 2:50 pm

What are your views on Lithium inhibiting noradrenaline and glucagon induced increases in cAMP, which essentially means inhibition of lipolysis??

  1. pseudonym November 8, 2017at 3:28 pm

I take 5mg LO (Lithium Orotate) every morning to counter fatigue from years of treatment resistant chronic insomnia. I’m now post menopause three years and add hot flashes and night sweats to the list of things that disturb my sleep. I first tried LO at night since so many people claim it helps with sleep, but from the very first night it kept me up all night, completely awake, alert and feeling rather upbeat. After a few nights of this I switched to taking LO first thing in the morning. With morning LO I have a better daily mood, more upbeat with more motivation and energy without being hyper, less brain fog and I feel less scattered mentally.

  1. Marie October 24, 2017at 7:43 am

Great article, thanks !

  1. Marsha October 23, 2017at 10:14 am

Good point. It was slightly confusing trying to figure which Lithium he was referring to– OTC Lithium Oretate (sp?) Or the one that you need a prescription.

  1. Jaime October 1, 2017at 10:50 am

Maybe Serotonin Syndrome? I’d check with a qualified Naturopathic physician if possible.

  1. Jaime October 1, 2017at 10:40 am

Good question. That’s what I was just searching for – what time of day is best to take Lithium Orotate? I took it yesterday evening and felt a pleasant relaxation. Didn’t knock me out tho it was rather gentle.

I’ve read it can actually help cancer.

  1. Jaime October 1, 2017at 10:38 am

Lori – same here! I have had severe mold toxicity and Chronic Inflammatory Response Syndrome for the past decade or two. Started w a new Naturopathic Clinic last week, and this was one of the first things they recommended. I was having to take Xanax occasionally again bc of the extreme severity of anxiety (likely caused by biotoxic environment and CIRS).

My Dad grabbed me a bottle yesterday and after a little research, I dove in. Wow! Within one hour I felt sooooo much more normal!! I do not feel like I am in a mental state of crisis anymore. Really, truly amazing. I was pretty skeptical… thank you, God. I pray this can continue to help me so that eventually I won’t need the Xanax even in emergencies. Well, this and a host of other Holistic treatment methods.

While I realize this is probably not The Holy Grail, I am just so hopeful. I am experiencing too much heightened sensitivies from the mold, and in dire need of something to assist this. We will be treating the mold asap, but for now, I actually feel less bothered by it!

Thanks for your comment bc it really resonated w me and I want to say a big “ditto” to all that! 😉 Many blessings to you and your path of healing. I understand feeling older. I am 34, but I have been feeling 84. No way to live!!

Jaime 🙂

P.s. I am taking 20mg Lithium OROTATE, 1x a Day.
Also, I cut out added sugars and gluten 1 year ago. I highly recommend this for anyone looking to reduce anger, hostility, aggression, etc…

  1. Sam August 30, 2017at 12:08 pm

Joe,

Are you still taking it? How come you stopped if it have brain protective effects?

  1. Hermes August 22, 2017at 2:11 pm

It’s important to distinguish low dose lithium orotate from the conventional high dose lithiumcarbonate. The references in this post refer to articles which are about the latter, of which the effect and side effects can’t be compared to low dose lithium orotate.
You might want to consider editing the article, and either make a clear distinction between the two or leave out the lithiumcarbonate, since it is a prescription drug which isn’t really relevant considering self hacking.

  1. Marina August 17, 2017at 7:35 pm

Have your renal function tests checked. (BUN and creatinine). Lithium can destroy kidneys, so be careful.

  1. Jordan July 22, 2017at 9:37 pm

Personally I know I overdid it, especially since I feel a bit sleepy now. I probably took 6 capsules at 5mg each. I figure I needed to flood my system at first since it was depleted with lithium.

I saw a few people complaining it caused them to gain weight. I hope they were talking about the synthetic version doctors prescribe because weight loss is a life-long battle and I don’t need another thing working against me.

  1. Jordan July 22, 2017at 9:33 pm

I felt suicidal and enraged for a while. I lost my job and I’m pretty angry at the world, especially since we’re always told lie after lie about how to be a success and it never works. I’ve been feeling worse as the months progress and I’ve not found a job. Immediately after I took lithium orotate, I felt better. The enraged feeling lifted from me and I feel calm. I tried magnesium previously, but it never made me feel this calm. Now I feel like someone could yell at me about anything and….meh. *shrugs shoulders*

Everyone needs to order this stuff off Amazon ASAP. I saw a few bottles for only $5.00. This works better than Prozac, which I can’t get anyway because I can’t afford the doctor’s visit.

  1. NL July 22, 2017at 7:28 pm

Wrong we are talking about OROTATE not CARBONATE jeesh!

  1. NL July 22, 2017at 7:19 pm

Did you read the article? It’s Lithium not calcium.

  1. NL July 22, 2017at 7:16 pm

It sounds like you are taking Lithium Carbonate not OROTATE which is completely different. Please don’t spread bad information.

  1. Balek July 22, 2017at 1:12 pm

@Tessa Zich

You could start her on Orotate, that’s not an issue. Perhaps 2.5mg, twice daily. You may first want to have her Lithium lvl tested however.

For her sleep, have her try deep breathing exercises before bed time, no high sugar foods before bed, no tv or video games, or surfing on her phone at night or while in bed. Pick up some Tension Tamer tea on amazon, & have her try a ZMA product (also on amazon). Make sure hee day is structured & she’s getting some exercise & is setting goals for herself. Lastly for her, if the aforementioned don’t work for her sleep, look into Nuvigil (for daytime alertness), and either Belsomra or Rozerem for her sleep. Lemme know if any of this helps.

  1. Balek July 22, 2017at 1:03 pm

How much Carbonate were you taking a day? Over 1000mg? And for how long did you take Lithium? I’m curious — as I just started taking 150mg only, & once per day. Also, did you have monthly Lithium lvl tests done?

  1. Eric July 12, 2017at 7:11 am

Hi there sorry to hear your daughters unwell. What has helped me significantly;high dose magnesium glycinAte(up to 700 mg per day elemental)and magnesium oil transdermaly, methylation support-methylb12,p5p,zinc,avoid folic acid and use small amounts of natural folate in b complex, lecithin for choline. Also a grain free diet with no processed sugars and high dha from salmon. I stopped focusing on saratonin and started looking at dopamine. Tyrosine can help raise dopamine. Avoid caffeine. Plenty sunlight, not enough to burn but to get a little pink, no sunblock this is for vitaminD. Avoid spiking and crashing blood sugar(no grains refined sugar or white potatoes). Plenty pastured farm eggs and organic greens or green smoothies. If there’s trouble digesting digestive enzymes before the meal. Last but not least ferritin levels at least 75, if low I use organic grass fed undefatted beef liver pills or just eat liver if you can stomach it. These things have helped myself and others when pharmaceuticals made the problem worse., but this is not advice since I’m not a M.D, ask your doctor before changing or altering any aspect of treatment. Also it could be possible that she has a mthfr gene mutation which is why I mentioned the methylation support above and the low ferritin is very common and causes extreme fatigue, poor sleep, high anxiety and low dopamine which causes depression. Really checking blood ferritin and making sure it’s over 75 would be my first step looking back. Just because a person is not anemic does not mean they have adequate iron storage thus ferritin tests. Also if currently supplementing iron if can throw the test off and show a high reading. Here’s wishing you the best!

  1. CAROL CLOSE June 30, 2017at 11:39 am

Aging is frequently paralleled by dehydration, which is considered to accelerate the development of age-related disorders. Dehydration downregulates klotho expression. Diuretics, like coffee and alcohol dehydrate you and down regulate anti-aging klotho protein. Sodium causes cells to excrete water and dehydrates you. Sugar draws water out of cells and dehydrates you. Asparagus, high protein, heat exposure, vigorous exercise, fever, diarrhea, vomiting or just not drinking enough liquid dehydrates you. Ironically, high sugar sports drinks can dehydrate you and down regulate anti-aging klotho. Lithium dehydrates you and down-regulates the longevity protein, klotho. There is a powerful effect of dehydration on klotho expression, an effect at least partially mediated by enhanced release of anti-diuretic hormone/vasopressin and aldosterone. An epidemiological study shows Mormons who don’t drink alcohol or coffee live longer. https://www.ncbi.nlm.nih.gov/pubmed/17920112 LIFESTYLE AND REDUCED MORTALITY AMONG ACTIVE CALIFORNIAN MORMONS
http://ajprenal.physiology.org/content/301/4/F745 DOWNREGULATION OF KLOTHO EXPRESSION BY DEHYDRATION
Lithium dehydrates you, too, and down regulates the longevity/anti-aging gene, Klotho.
https://link.springer.com/article/10.1007/s00424-013-1340-y REGULATION OF MINERAL METABOLISM BY LITHIUM. Lithium downregulates Klotho because dehydration downregulates Klotho, the anti-aging longevity gene. Lithium treatment significantly increased renal GSK3 phosphorylation, enhanced serum ADH and FGF23 concentrations, downregulated renal Klotho expression, stimulated renal calcium and phosphate excretion, and decreased serum 1,25(OH)2D3 and phosphate concentrations. In conclusion, lithium treatment upregulates FGF23 formation, an effect paralleled by substantial decrease of serum 1,25(OH)2D3, and phosphate concentrations and thus possibly affecting tissue calcification.
Any comments on lithium verses enhancing Klotho expression?

  1. carol close June 30, 2017at 7:43 am

Preclinical studies have shown that lithium modifies pathological cascades implicated in certain neurodegenerative disorders, such as Alzheimer’s disease, Huntington`s Disease, multiple system atrophy and amyotrophic lateral sclerosis. Positive effects of lithium on neurogenesis, brain remodeling, angiogenesis, mesenchymal stem cells functioning, and inflammation have been revealed, with a key role played through the inhibition of the glycogen synthase kinase-3, a serine/threonine kinase implicated in the pathogenesis of many neuropsychiatric disorders. Lithium reverses aging by restoring a cell’s ability to divide as an ATM inhibitor.  These recent evidences suggest the potential utility of lithium in the treatment of neurodegenerative diseases, neurodevelopmental disorders, and hypoxic–ischemic/traumatic brain injury, with positive results at even lower lithium doses than those traditionally considered to be anti-manic.  Lithium showed evidence for positive effects on cognitive functions and biomarkers in amnestic mild cognitive impairment (even with doses lower than those used for mood stabilization). Studies of lithium in Huntington’s disease, multiple systems atrophy and CSI did not show benefits of lithium. However, due to methodological limitations and small sample size, these studies may be inconclusive. Studies in amyotrophic lateral sclerosis showed consistently negative results and presented evidence against the use of lithium for the treatment of this disease.

  1. carol close June 30, 2017at 7:38 am

REVERSING AGING NOW POSSIBLEAging is a phenomenon in which a cell’s ability to divide and grow deteriorates as it gets older, and this causes degradation of the body and senile diseases. The inhibition and recovery of aging is an instinctive desire of humans; thus, it is a task and challenge of biologists to identify substances that control aging and analyze aging mechanisms. DGIST’s research team have been conducting research to reverse the aging process by shifting the existing academia’s ‘irreversibility of aging’ paradigm, which means aging cannot be reversed. To reverse the aging process, the research team searched for factors that could control aging and tried to discover substances that could restore cell division capacity. As a result, it was confirmed that KU-60019, an inhibitor of ATM protein, which is a phosphorylation enzyme, recovers the functions of aging cells through activation of lysosomal functions and induction of cell proliferation. The degradation of lysosomes, which are intracellular organelles responsible for autophagy and decomposition of biopolymers such as proteins and lipids in the cell, leads to cell senescence by accumulating biomolecules that must be removed in cells and causes instability of the metabolism such as removal of dysfunctional mitochondria that do not function. The research team was the world’s first to confirm that as cell aging progresses, the vacuolar ATPase (v-ATPase) protein involved in the lysosomal activity regulation is phosphorylated by the ATM protein, and the binding force between the units constituting the v-ATPase is weakened, so consequently the function of lysosomes deteriorates. In addition, the team has proven that the reversible recovery of aging is possible through its experiment that shows the regulation of ATM protein activation by KU-60019 substances induces the reduction of phosphorylation of v-ATPase, thereby inducing recovery of mitochondrial function and functional recovery of the lysosome and autophagy system as well as promoting wound healing in aging animal models. (Hey- Positive effects of lithium on neurogenesis, brain remodeling, angiogenesis, mesenchymal stem cells functioning, and inflammation have been revealed, with a key role played through the inhibition of the glycogen synthase kinase-3, a serine/threonine kinase implicated in the pathogenesis of many neuropsychiatric disorders. I remembered lithium and put it together that lithium is most likely KU-60019).

  1. Tessa Zich June 12, 2017at 10:42 pm

This has been incredibly helpful! Thank you all for posting your research information and your personal struggles and triumphs. I started taking the 5mg tablets off and on because I wasn’t sure of the safety, about a month ago. I can tell that I feel better when I take it.
My question to the group is that I have a 16 year old daughter who we’ve been desperately trying to help with her anxiety and depression since she was two years old. Nothing is helping her. Should I try the lithium orataye that I’m taking? My only concern is that she is taking fluoxetine. Can she take both at the same time? She constantly tells me how tired she is but yet she can’t sleep and how depressed and anxious she is all the time.
I am at my wits end. I love her so much and just don’t know what to do any more.
She also takes trazadone to sleep but she only takes an 1/8 of a mg. If she doesn’t take it, she doesn’t sleep at all but if she does take it she feels as if she needs to sleep all the time.
For me, I’m already 30 pounds over weight. Is there anything I can do to offset the weight gain if it starts?
Thanks so much in advance if anyone is able to read and respond to these inquiries.
I wish you all happiness and wellness!
Tessa

  1. Emmie May 30, 2017at 1:12 am

Thank you, Christian, for your comment.
Do you know how much lithium orotate would do the same job as 400 mg lithium carbonate ?
( my daugther still takes the lithium carbonate. She is doing a lot better though , after stopping gluten, nightshades and beans.) , still she is too frightened by the idea to have another depression, to stop the lithium.

  1. twobar April 26, 2017at 5:32 am

Hi, I realize this is a old post but I’m curious why lithium goes low in the blood? I was tested through the blood and almost have zero? My B12 is low as well? I’m also toxic to plastics due to my job over 10 years. I’m detoxing now with supplements and a infrared sauna, but could toxicity be the reason for lithium to go low and once that’s fixed the lithium will stabilize?

  1. Melanie R Jones February 25, 2017at 5:13 pm

Lithium ruined my life. It did nothing for my depression but it immediately piled on 100 pounds, gave me diabetes and probably influenced the development of carcinoid syndrome. It’s not the wonder drug for everyone.

Me to but that was at prescription levels. !! Low dose is a totally different animal! I am thankful I tried it ..helps my depression and anxiety plus cognitive fog.

  1. j February 18, 2017at 9:40 pm

Is there even any evidence that low dose lithium promotes neurogenesis?

  1. jane December 15, 2016at 9:31 pm

What is the actual dose of the Lithium ions in mg in the lithium orotate 5mg dose?

Does the reported 1.5 mg dose on the Trace Minerals label refer to the Lithium ions only? I would assume so, since the salt is dissolved in the solution, but the label does not so state.

Thanks,
Jane

  1. RK October 28, 2016at 10:38 am

Where do you find lithium orotate 1mg? The lowest dose I can find is 5mg and that is with n acetyl-cysteine. I do not tolerate n acetyl-cysteine. Thanks.

Trace minerals Concentrace drops have 1.5 mg lithium orotate per 1/2 tsp

  1. Rathmullan October 24, 2016at 7:42 pm

Is it safe to combine the aspartate and orotate forms of lithium. That is, to take both forms in a single day?

ya

  1. Emmie September 21, 2016at 2:27 am

We live in Europe. My daughter takes 400mg lithium carbonate a day for BiPolar Disorder. She is doing well and works successfully in a creative job. She does have lithium induces skin problems and problems with her intestines ( not every day ) . Would extra magnesium and inositol be bad for her ? She takes now active B vitamins and magnesium ( and more ).
Would it be a good idea for her to ask for lithium orotate and then in a lower dose ?
( I understand perfectly weel if you do not know the answers ).

Next week we will try your SelfDecode.

Be cautious the bi carbonate version your daughter is taking is very different from orotate. Orotate crosses the blood brain barrier where as bicarbonate does not, hence the high dosage. With lithium Orotate a very small dose is all that is required to effect a positive outcome with little side effects.

I hope you have your daugther off the carbonate type of Lithium now. I took it for about 2 years and its really bad in the long run. FIrst its good, then it gets bad. That is because Lithium carbonate intoxicates the body the longer you take it. Your daughter should inform herself about detoxing. Lithium orotate is great ! im only speaking of that s!it the doctors give you.

  1. Lori Bernardo September 13, 2016at 4:39 am

I just started it yesterday. I am amazed how calm I feel. I have autoimmune and stuggle with brainfog, ear ringing, poor memory, inflammation, insomnia, anxiety and depression. My ear ringing is less, I can think clearer and my inflammation is a lot less. Brain fog and fatigue is a lot better. I have chronic fatigue. I am hoping it will reverse some of my brain issues. I am 50 and am tired of feeling like I am 90.

I am a bit confused. All of these benefits happened in one day? Are you still seeing improvement?

Dante….I did not post but want to comment and the only way I could figure was to hit reply….I noticed less aggression in 2 hours….No LIE….I was honestly FRANTIC FRANTIC FRANTIC on the day I started this and HONESTLY felt better in 2 hours. I thought this feeling was Pychosymatic but after reading all the others and the immediate and dramatic effects I would have to say YES it works VERY QUICKLY : )

was this the actual drug, calcium time released calcium carbonate?

  1. DC September 6, 2016at 4:09 pm

I have a rage disorder along with obsessive thoughts. 30 mg of this lithium orotate daily has dramatically changed my life. I feel that 40 mg is what my brain needs. Is this okay long term? Will I need to discontinue for my upcoming surgery? I really do not want to stop taking it. Thank you for your time.

I would look into other gsk3b inhibitors.

  1. Joy September 2, 2016at 5:14 am

Oh help help! I’m looking for a comparison of liquid ionic lithium and lithium orotate. I’ll divide each 5mg capsule into 3 capsules every day for the rest of my life if I have to but it sure would be nice to switch to the liquid. I just want to be certain of dosage. Can’t say enough about it, except it’s too bad I had to suffer from anxiety, mood swings, difficulty focusing, side effects of prescription meds for over 50 years before I found lithium orotate.

  1. jtj July 30, 2016at 5:32 pm

Why have you chosen to leave out the life threatening side effects, like diabetes insipidere ?

Reference?

Lithium carbonate has all of those dangerous life-threatening side effects but lithium orotate or lithium acetate do not have those because they have not been changed

You’re thinking about the pharmaceutical lithium, which is 300+ times stronger. Please research the difference.

Check your facts before you start spouting incorrect information please. This discussion is about Lithium Orotate Not Bi Carbinate !! Do your research

Two of the big differences is that oratate is absorbed better and crosses the “blood-brain-barrier” more effectively, meaning much smaller doses can be used. The doses used in l.carbonate are close to toxic and need to be monitored. My ex-wife actually went toxic on a prescribed dose and suffered amnesia for a while (the real kind, not the fictional version). The above poster mentions pharmaceutical lithium is “300+ stronger”, but what I think he means is that many times the amount of lithium carbonate is needed to provide the same amount of lithium ions to the brain. Why haven’t medical practitioners switched? It cost at least tens of millions of dollars to do the effectiveness and safety tests. Pharmaceutical companies need to forecast high profit margins to do these tests and market the alternative forms of lithium. That money just isn’t there according to finance. In a way, lithium carbonate is a kind of scam by neglect. Think Big Pharma and medicine isn’t capable of that? Tell me where the new antibiotics that are so desperately needed? Why are so many dying of hospital infections. If you want better living through chemistry, you need to do your own research.

  1. erna edwards June 25, 2016at 7:56 am

Can you drink alcohol while taking lithium orotate?

  1. loane May 12, 2016at 8:51 am

I used one capsule of lithium orotate 5mg from Swanson… my blood glucose from 88mg/dl went to 136mg/dl. Is this normal?

  1. TH April 20, 2016at 6:28 am

do you know what form the lithium in that trace mineral water supplement is?

  1. Lee Horner January 20, 2016at 11:58 am

How do I determine what different types of Lithium work best for what symptoms?

  1. Santino January 18, 2016at 9:34 am

Hello Joe,

is Lithiumaspartate also ok? Or would the aspartate be harmful?

It’s fine

  1. Simi December 11, 2015at 5:10 pm

Some research shows Lithium orotate to be beneficial for Inflammatory bowel disease but this article says not to take in Crohn’s??

Post that research please!

  1. Devildog December 10, 2015at 7:46 am

Hi Joseph,

In my Lithium Orotate studies, I just came across your site. I am on the tail end of 61 and have been burdened by Adult ADD for decades. All of my life actually looking back. Conventional drugs had more negative effects than positive, so I couldn’t continue with them. And so called natural remedies failed to work miserably. Then a few weeks ago I stumbled across information about lithium orotate on the internet and I have been reading everything I can get my eyeballs since.

Today is my second day of taking 20mg of it. I determined that 20 mg once a day is more than safe since this form of lithium has not proven to be toxic at much higher dosages. I believe it is a high enough dose to have an affect, if it is going to have an affect on me and I am withholding judgment for at least 30 days…unless I get a positive/negative result too obvious to ignore earlier. Too early to report any affects yet, but I am highly encouraged by all of the research (although no large scale trials have been performed that I have read of) and testimonials from users across the web about how it has finally solved their or their children’s various issues that meds and other remedies had failed to perform or presented too many negative side effects to be able to enjoy any positive benefits received.

I am looking for relief from issues around lack of focus and the inability to stay on task for any length of worthwhile time. As well as with maintaining motivation to finish projects. The suggested long term benefits regarding increased general brain health will be appreciated also, but immediately, help with lack of focus and my brain from switching channels too often to allow for completing tasks in a timely manner or at all.

Great site you have here. I will sign up for updates. Thanks.

At the Optimal House, we’ve got a lot of tricks to help attentional issues 😉

So, how is it going now?

  1. Samantha December 2, 2015at 11:47 pm

Hi! Are there any other drugs, supplements, or herbs that should not be mixed with Lithium Orotate? I’d like to know before I start taking it.

None that I know of with a dose of 5mg…

  1. Kevin November 13, 2015at 1:07 pm

Question: Do you think that chronically administered, small (+-6mg) doses of lithium orotate would, over time, increase the amount of grey matter in the brain? I believe the studies point to a therapeutic level of lithium used for 4 weeks or so… Thanks!

  1. JoAnn May 13, 2015at 10:44 pm

“This confirms that the benefits of other lithium salts prescribed by doctors can be achieved through the orotate version commonly sold.”
Suggest “that some of the benefits”

Ok

  1. Lithium Orotate April 16, 2015at 7:47 pm

Thanks for getting the word about lithium orotate out there. Your site is very helpful and the community thanks you for it. Keep up the great work man

  1. Aristophanes’ Beetle January 28, 2015at 7:32 am

And don’t forget it’s impact on thyroid physiology. Lithium is not an antipsychotic. It is used as a mood stabilizer particularly effective for suicidal ideation and behaviors in bipolar depression and mania both of which can occur without psychotic symptoms per se, psychotic symptoms being defined as symptoms/ signs indicating lack of insight/ judgment/decision making logic out of conjunction with consensual reality (that is for a philosophical/ linguistic discussion). Lithium also works through the inositol system: http://www.bipolar-lives.com/inositol-and-bipolar.html and http://en.wikipedia.org/wiki/Inositol_monophosphatase. Due to the narrow therapeutic vs toxic window for lithium dosing it’s probably to the well being of all beings to state a very strong caveat that dosing for recreational experimentation is highly likely to cause irreversible cerebelar damage and we know how much we hate that when it happens. Thanks for this treasure trove work in progress.

My understanding from this article and other ones was that Lithium Orotate is not so easy to overdose on…. is there clinical evidence to the contrary?

  1. K January 18, 2015at 2:39 pm

Would 1mg per day do all this wonderful things for the brain as you say, would 1 mg effect my sleep?

  1. K January 18, 2015at 2:27 pm

Can you get enough lithium from your food instead of supplementing ?

No

Though not food or supplement, Rogaska Donat Mg Mineral water available has not only 1mg/liter Magnesium (which I seem to need badly for my deficiency), but additional 3 mg/liter Lithium.

Sorry for my typos, meant to say 1 GRAM/liter Magnesium, and which is available at least here in Europe.

  1. K December 20, 2014at 10:48 am

Should you have your diet and life style in check first before using Li, maybe just a multi vit,

Nah

  1. Britt December 6, 2014at 12:08 am

I’m thinking that some bipolar is caused by a mild form of thyroid instability, switching back and fourth between hypo and hyper and the reason MDs put patients on such high doses that almost cause toxicity and almost always cause tremors is they need to see a stabilization affect sooner rather than later–instead of letting it build up over months and letting the patient’s body get used to it. But that’s an anecdotal guess.

But really how much of Medical Science is just guesses anyway, a ton of persciption meds I see say “Medicationon is thought to work by XYZ.” emphasis on the “is thought.”

Studies?

  1. YimYam October 11, 2014at 4:59 pm

Lithium @ 2.5mg increases symptoms and increases anxiety, should I be tested for Crohns, again? Or is there anything else you can advise for me to do?

Weird, no

Again I noticed today after taking it that I experience anxiety a couple of hours after ingesting it….very weird. Epilepsy related?

Teeth grinding, relatively stimulated and feeling on edge/anxious and a bit panicky. I never usually experience this feeling.

  1. kiki September 28, 2014at 10:16 am

Hi, Can you give reference to where you found Lithium Orotate increasing IL-8 and can make intestinal issues such as Chron’s worse? I only find studies that show it helps reduce intestinal inflammation?

I did. Click the “(R)”

  1. K September 27, 2014at 10:26 am

Joe you say about not taking smart drugs as you are better off taking natural stuff instead so how is this any different as it is a drug after all, Why cant you just eat veg and fruit would that not do the job, Is it because of this freaking modern world? Can it ever just be simple? You are a smart man.

It’s actually a mineral

  1. Rae September 10, 2014at 6:30 am

Taking lithium orotate for 2 months. First month a miracle!! Nothing bothered me and Now I feel irritable anxiety and pissed off mode all the time. Any suggestions???

Maybe taking too much?

  1. Kieron June 7, 2014at 6:36 pm

does li effect the pinal gland, I need my third eye to work at its best

Try Chaga mushroom. It has high melanin levels and activates the pineal gland.

don’t know

you are correct!!!

  1. chris May 5, 2014at 10:34 pm

I have two questions. One is I’ve been taking orotate because I read one review saying it was the best then I recently saw one saying orotate can lead to cancer. What are your thoughts on this? My second question is what time of the day do you take it? I’ve been doing the morning but I read on another forum someone said they take it at night and it helps them go to sleep. If that’s the case is taking it in the AM making me tired during the day?

Take in AM,
Doesn’t cause cancer. Reference?

  1. Pako February 20, 2014at 4:08 pm

Any thoughts on 5mg lithium oratate and hypothyroidism?

  1. Steve February 11, 2014at 8:26 am

Ive been taking Li for a month now and it deals with anxiety/mania. However, it does make you hypothyroid.

  1. Chrono Cross February 10, 2014at 7:55 pm

Ooo I’ll try this out. I had a question though, I know that the prescription lithium requires blood tests to make sure it doesnt get to toxic levels. I assume with this OTC lithium the dose is too low to warrant blood tests or is it due to something else?

Hi CC,
you are correct in that it’s the lower dosage that makes it less toxic. Supposedly it gets absorbed better so you need to take less.

With Lithium Orotate the delivery mechanism is straight into the blood and brain allowing for much lower dose which is no. Toxic levels. Lithium carbonate on the other hand requires massive amounts to a hive the same effect which can be very toxic. Bottom line stick with over the counter Orotate