Introduction

Lithium has uses beyond its traditional role in manic depressive illness (a.k.a. bipolar disorder) and recent discoveries indicate these may expand. It has a use in treating some blood disorders, and has now been shown to have neuro-protective properties which may be relevant in Stroke, Alzheimer's and Parkinson's and other forms of nerve of insult and injury, including peripheral nerve injury. Some of these effects are manifest at lithium levels below those usually used in BPD. It is therefore helpful to have a wider understanding of lithium in the environment, diet and body.

Units of measurement

Lithium mg/L or mmol/L (for lithium meq and mmol are equivalent).

1 mg/L = 0.144 mmol/L. 144 micro µmol/L (micro-mol/L)

1 mmol/L = 6.94 mg/L.

Medical laboratory assays usually use mmol/L, so for blood tests during lithium treatment, levels are usually reported in mmol/L, or meq/l, which for lithium is the same thing. Levels considered therapeutic for Manic Depressive illness (Bipolar Disorder) are around 0.5 – 0.8 mmol/L (or 3.5 – 5.5 mg/L) which are usually achieved with daily doses of about 400 – 1200 mg of lithium carbonate. In humans, lithium toxicity may sometimes occur at serum levels of about 1.0 mmol/L, and is expected at 2.0 mmol/L. Levels in humans are usually referred to samples taken 12 hours post-dose; most published research quotes levels done 12 hrs post-dose.

NB the lower limit of detection/quantification (LOD/LOQ) for most methods of laboratory estimation of lithium is around 0.2 mmol/L, or 1.4 mg/L (1-3). Immuno-assays may give false low readings when lithium levels are elevated because of the so-called “hook effect”, but that method is not used by many laboratories (4, 5).

Lithium Concentrations in Water Sources

Lithium is ubiquitous in the cosmos, being one of the three elements present early after the creation of the universe in the ‘big bang’. It is unevenly and sparsely distributed in the earths’ crust and that is reflected in enormous variations (from 1.0 mg/L down to 0.000005 mg/L) of its concentration in water supplies (6-9). The concentration of lithium in surface waters is generally minute (~ 0.002 mg/L), except in specific locations (e.g. in South American Andes mountains) where streams flow over granitic rock gravels high in lithium containing minerals (pegmatites) where levels can reach around 1.0 mg/L (10, 11).

Levels in sea-water are around 0.2 mg/L which is about one hundred times higher than the median fresh water level (i.e. 0.2 vs. 0.002 mg/L).

Sea water has a Lithium concentration range of 0.140 – 0.250 mg/L, (0.14 – 0.25 parts per million) (12): some Andean brine sources like the famous “Salar de Atacama” (a salt flat in Chile which is a prime world source of lithium) have 1,000-3,000 mg/L.

Until recently, there was sparse data on lithium in rivers, ground-water or tap-water (see Kszos for references and details, especially re N. America (13, 14).

Now, recent extensive European data (8) indicates that in ‘fresh’ (surface) water lithium is usually very low, median 0.002 mg/L (10), but ranges from <0.000005 to 0.356 mg/L (values based on over 800 samples from all over Europe). Lithium in bottled water in Europe (i.e. underground bore-hole/spring-water) has been assessed at 884 different sites which yielded: median level of 0.010 mg/L, range <0.0002 to 9.9 mg/L (7-9).

Levels in tap water reported in the psychiatric literature are less representative or reliable: typical values given recently have been around 0.0001 to 0.06 mg/L of lithium (15-17). The mean level in Austrian drinking water was 0.01 mg/L, in which the highest single lithium level was 1.3 mg/L (18). In Japan levels in the drinking water of 18 municipalities in the Oita prefecture ranged from 0.0007 to 0.06 mg/L (15).

There are many famous mineral spa resorts throughout the world, some of which may have lithium levels as high as 10 mg/L (7-9, 14). There is a history going back before the 19th century of such spa waters being recommended for nervous afflictions, but no evidence that anyone recognised specific anti-manic efficacy (and of course no great expectation that there would be any). Lithiated waters were much esteemed in the early 20th century and the well-known beverage “7-Up” started as a lithiated citrus-flavoured tonic. This was changed when regulations were introduced in the USA in 1948.

For data and references on toxicity to aquatic species, again sparse, see (13).

Lithium in Animal and Human Diets

Until recently there was little data available on lithium in water and foodstuffs, consequently opinions expressed have been a mixture of guesses and approximations (e.g. the EPA recommendations and estimates below).

Typical human dietary intakes estimated by the US EPA (Environmental Protection Agency) were 0.65 – 3.1 mg/day (17), but that estimate may be outdated, and is higher than the more recent, comprehensive and accurate estimate of 0.5 mg/day derived from the Second French Total Diet Study (TDS 2) (19-22), see below.

Note: the 2002 Schrauzer paper has a lot of non-peer-reviewed and secondary references of uncertain provenance and accuracy: it may be misleading in some important respects. Schrauzer was one of the first authors to publish about lithium in drinking water, and crime, suicide and arrests (23).

More recently lithium intake has been estimated to be around 0.2 mg/day (24), which is more in line with the TDS2 figure of 0.5 mg (see below).

The EPA had recommended that the concentration of lithium in the drinking water supply should not exceed 0.7 mg/L (it would be difficult to reach that level, even if you tried). No western countries presently specify limits for either lithium, cobalt, tin or vanadium.

Many municipal reticulated tap-water supplies are orders of magnitude below the EPA maximum 0.7 mg/L, often < 0.001 mg/L (a mean of 0.002 mg/L (10)).

Trace elements/minerals are usually defined as those that are required in amounts between 1 to 100 mg/day by adults. The trace mineral group includes iron, copper, and zinc.

Ultra- or micro- trace elements/minerals are defined as those that are required in amounts of less than 1 mg/day. They include chromium, manganese, fluorine, iodine, cobalt, selenium, silicon, arsenic, boron, vanadium, nickel, cadmium, lithium, lead, and molybdenum. As an aside it is worth noting that standardised laboratory rat feed has the following constituents as micro-nutrients (in microgram amounts) zinc, manganese copper, selenium, molybdenum, chromium, lithium, boron, nickel, vanadium and fluoride (25). The inclusion of lithium in that list reflects the evidence, reviewed by the experts who compiled it, relating to relevant physiological effects of lithium on laboratory animals.

Current evidence indicates lithium is an essential, or at least beneficial, dietary ultra-trace element in animals and also humans, with a relevant physiological function in vertebrates. The totality of research on this is still modest and I suspect more research will be commissioned related to the rise in the use of lithium batteries and electric powered vehicles, and the consequent risk of ground-water contamination when such things are disposed of, or recycled (e.g. see (14).

Animals

The normative dietary lithium requirement of animals (goats, rats, pigs) amounts to < 2.5 mg/kg (food dry weight). Edible food crops may contain elevated lithium concentrations, which is highest in the leaves, e.g. 20 mg/kg (26), which suggests ruminants may ingest substantial amounts. Lithium also accumulates in most marine organisms, and particularly in fish flesh (27).

Goats and rats fed lithium deficient diets exhibit less than optimal reproductive and general health (17, 24, 28-30), and plants grow less vigorously. Lithium has been claimed to enhance longevity in metazoans (31).

There are few measurements of lithium levels in the blood or flesh of edible animals or fish etc. (32).

Lithium Intake in Humans

The typical total daily lithium intake from dietary sources has been quantified recently from the huge French “Total Diet Study” at 0.5 mg/day (19-22).

That indicates tap-water constitutes a fraction (around one tenth) of total lithium intake for most populations. Note that the French Total Diet Study (TDS 2) figure of 0.07 mg/L for lithium in ‘water’ includes bottled mineral waters, it is not just tap-water. The TDS2 estimate is that lithium in ‘water’ is ~ 35% of the total daily intake, followed by coffee (17%) and other hot beverages (14%).

TDS 2 contains the largest sample of assays of lithium in foodstuffs that exists. Most foods were assayed at concentrations of thousandths of a mg/kg (i.e. 0.001 – 0.009 mg/kg). The following had concentrations, in rank order, of > 0.02 mg/kg: - crustaceans and molluscs 0.07, pulses 0.06, coffee 0.044, pasta 0.042, rice and wheat products 0.04, Soups and broths 0.023. Just below those came vegetables (as a general category) at 0.019, dried fruits, nuts and seeds were 0.017, potatoes 0.016, eggs 0.011. Fish, at 0.01 was almost 10 times lower than crustaceans (19, 21, 33).

The evidence thus seems to be that tap-water constitutes a small fraction of lithium intake and that is also supported by the useful work of Bochud et. al. (34) (see Lithium in the Environment, Diet and Body: Pt 2).

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