Bismuth and Lithium
Bismuth (Bi) and Lithium (Li) are associated trace elements. While bismuth is not classified as essential for humans at this time, lithium is a nutritionally essential trace element with a potential to decrease mortality, and provide anti-aging capabilities.[1][4] Although not related on the Periodic Table of Elements, bismuth and lithium are biologically associated on a gastrointestinal and mental health level. While lithium is better known for its therapeutic properties with bipolar / manic-depressive disorder, both elements exert a similar effect on their respective chemical environment: Lithium in regard to potassium / sodium balance, and bismuth in regard to phosphorus / zinc balance.
The case for lithium as a nutrient has strengthened since this was written, although it is still not official. No authority has set a Dietary Reference Intake, RDA or Tolerable Upper Intake Level for lithium, and the 1 mg figure in the reference table below is a provisional intake proposed in the nutritional literature rather than a derived reference value.[4] What has changed is the evidence behind the idea. Of all the major and trace metals assayed in human brain tissue, only lithium was found to be significantly reduced in the prefrontal cortex of people with mild cognitive impairment or Alzheimer's disease.[3] That is a post-mortem measurement, not a trial in living patients - but it is the first substantial support for treating lithium as a required trace element rather than only as a drug.
Shared toxicity / overdose symptoms of bismuth and lithium include kidney or liver damage, hypoadrenalism (bismuth), hypothyroidism (lithium), mental confusion, staggering gait, tremor, memory problems, and others.
Neither element has a nutritional antidote. Lithium poisoning is a medical emergency, not something to manage at home. Treatment is intravenous fluid resuscitation and, in severe cases, haemodialysis, which the international EXTRIP workgroup recommends as the treatment of choice.[14][15] Blood levels rebound as lithium re-equilibrates out of the tissues, so dialysis is repeated until the level stays below 1.0 mmol/L.[15]
Bismuth encephalopathy is managed by stopping the bismuth, after which recovery generally follows over weeks to months.[18][19][20] Chelation is not routine and may make matters worse: giving the chelator DMPS raised urinary bismuth excretion while the patient deteriorated clinically.[19] No mineral supplement forms part of the management of either.
Lithium's established clinical use is in Manic-Depressive Illness, where it remains an evidence-based maintenance treatment in systematic review and network meta-analysis of randomised trials.[5] The other indications it was once put forward for did not survive testing. In Huntington's Chorea, a double-blind crossover trial of lithium carbonate, haloperidol, the two combined and placebo found no significant effect on chorea by any treatment,[12] and a placebo-controlled trial reached the same conclusion.[13] In alcoholism, a Department of Veterans Affairs cooperative study randomised 457 men over 52 weeks and found no difference between lithium and placebo, in depressed and non-depressed drinkers alike.[11] For Ménière's disease no adequate controlled evidence was identified.
In animal models, lithium has been reported to be beneficial for brain injury, spinal cord injury, stroke, Parkinson's disease, and ALS (amyotrophic lateral sclerosis). That did not carry across into people. Four randomised controlled trials totalling 469 ALS patients were pooled in a meta-analysis which found no benefit for survival, for the ALS functional rating scale, or for forced vital capacity,[8] and the phase 3 LiCALS trial found no survival advantage at 18 months.[9] One narrow signal survives: a possible survival benefit confined to patients homozygous for the C-allele at rs12608932 in the gene UNC13A, which a confirmatory trial was designed to test.[10] That is a question about one genotype, not a treatment for ALS.
Raising below-normal levels of lithium or bismuth can, but does not have to produce any positive effects in regard to mental health, since few lithium or bismuth-deficient individuals present with actual mental illness, although some researchers claim that areas with the highest lithium levels in drinking water have the lowest rates of homicides, and the lowest mental hospital admissions (those findings have not been officially accepted).
That literature has grown considerably since. A systematic review and meta-analysis found an inverse association between lithium concentrations in drinking water and suicide mortality,[6] and a larger synthesis covering 2,678 regions and 113 million people reported the same direction of effect.[7] The qualification in the sentence above still holds, and for a specific reason: these are ecological studies, which compare whole populations rather than individuals. They cannot show that a given person's risk changes if they supplement lithium, and they were not designed to.
When indeed indicated for bipolar disorder,[2] patients typically present with low lithium levels and very high sodium levels, whereby lithium provides a balancing effect. The intake of higher amounts of lithium has a tendency to raise sodium, and frequently also potassium through its effect on kidney functions, and it has a tendency to raise manganese through its effect on liver functions (which depresses thyroid activity), so there is a distinct biochemical conflict that has a genetic basis. Otherwise everyone with low lithium levels (which are actually quite common), would be suffering from manic-depressive episodes. Regardless, it is estimated that lithium resolves Manic Depression in about one third of patients; it is said to improve the lives of another third, and is ineffective for the rest.
One inference has to be blocked here. Lithium's benefit in bipolar disorder is established by randomised trials at prescription doses under serum monitoring,[5] at intakes 75 to 450 times anything obtainable from food or a supplement - see the note beneath the reference table below. A treatment working does not mean a nutrient was missing. No evidence was identified that a measured lithium level identifies who has the illness, or predicts who will respond to treatment, and bipolar disorder is not a nutritional deficiency. It is not a condition to treat with a supplement, and the passage above should not be read as suggesting otherwise.
The same qualification applies to the levels themselves, and to the references elsewhere on this page to individuals being lithium or bismuth deficient. No validated biochemical marker of lithium status exists: no lithium-sensitive protein or enzyme is known that reflects dietary supply. Status can only be estimated from plasma or urinary concentration, and the work of characterising what those concentrations mean in ordinary people, and how little is established about lithium status in the general population, is recent and still in progress.[25] A finding that low levels are “quite common” therefore describes readings measured against an assumed range, rather than a deficiency that can be diagnosed. For bismuth the position is simpler still: it is not an essential element, so there is no deficiency state for a reading to indicate.
Bismuth and Lithium frequently test low in patients who suffer from low stomach acid levels corresponding to upper (bismuth) and lower (lithium) parts of the stomach, and they are invariably always low in those with an active infection of the Helicobacter Pylori bacterium, which is responsible for some gastric ulcers and a number of other medical conditions (see "H. Pylori" for details).
Bismuth, through its antimicrobial action, is more appropriate for peptic involvement to inhibit H. Pylori activity, where it supports an increase in upper stomach acid levels, while lithium is more indicated for lower gastric / duodenal involvement, where it supports an increase in lower stomach acid levels.
Bismuth's antimicrobial action against H. Pylori is real, and it is the best-supported claim on this page - but not as bismuth on its own. Bismuth raises eradication rates when it is added to a multidrug regimen alongside a proton pump inhibitor and antibiotics, which a systematic review and meta-analysis confirms.[21] Bismuth quadruple therapy is a standard regimen for the infection; bismuth by itself is not a treatment for it.
The statement that both elements are “invariably always low” during active infection was not addressed by any study identified, and no evidence was found that a measured level of either element indicates infection, gastric acidity, or response to treatment. Bismuth is also not classified as essential for humans, so there is no established bismuth deficiency to be low in.
