Lithium: An Element with Potential for Biostimulation and Biofortification Approaches in Plants

Abstract

Lithium (Li) is the lightest metal in existence. Its effects on higher plants are still under discussion because both positive and toxic results have been reported in different species. In the last decade, the use of Li has increased considerably, and it is projected that Li waste will be an environmental problem in the near future, such that various organisms, including plants, may be altered by its presence. Interestingly, Li can trigger hormesis, with beneficial effects at low doses and inhibitory or harmful effects at high doses. Currently, numerous research groups are focusing their studies on agriculture to obtain crops fortified with Li, which represents a nutritional advantage in food if adequate concentrations are used. However, more studies are still needed in order to understand the biochemical mechanisms of the effects of Li on plants. This review describes the natural and anthropogenic sources of Li, as well as the concentrations of this element in different environments. Regarding the uses of Li in different areas, topics related to doses that cause toxicity and lethality in humans are addressed. Given its impact on crop production, mechanisms of Li uptake and transport in higher plants are reviewed, as well as the effects on plant metabolism and physiology. Likewise, the perspective on the controlled use of Li in biostimulation and biofortification of crops is addressed.

1. Introduction

Lithium (Li) is the lightest alkali metal, with an atomic mass of 6.941 g mol⁻¹, a density of 0.53 g cm⁻³ at 20 °C (half that of water), and the highest negative electrochemical potential among metals; it has a melting point of 180.54 °C, a boiling point of 1342 °C, an oxidation state of +1, and an atomic number of 3 [1,2,3]. It is silvery-white, with an atomic radius of 0.157 Å, an ionic radius of 0.60 Å, and an ionic potential of 1.47 Å [4]. Its name comes from the Greek word ‘lithos’ that means stone. It received this name because it is present in all rocks. It was discovered by the Swedish chemist Johan August Arfewdson in 1817 [5,6]. Its effects on higher plants are controversial because it exerts toxic effects when applied at high doses, whereas it stimulates growth at low concentrations [2,7].

In humans, Li is not bioaccumulative, as it is eliminated 24 h after ingestion [8], and its compounds generally have low toxicity (

Table 1. Physical and chemical properties of lithium (Li) and its main compounds [1,10].

Name (Formula)	Atomic Mass (g mol−1)	Oxidation State	Boiling Point (°C)	Melting Point (°C)	Density (g cm−3)	Solubility	n-Octanol/Water Partition Coefficient (Log KOW)
Lithium (Li+)	6.94	+1	1342	180.54	0.53	---	---
Li molybdate (Li2MoO4)	173.82	+1	---	700.00	2.66	Highly water soluble	---
Li hydroxide (LiOH)	23.95	+1	450	924.00	1.46	Water soluble	≈0.00 a
Li chloride (LiCl)	42.39	+1	1382	614.00	2.07	Water soluble	−2.66
Li carbonate (Li2CO3)	70.02	+1	---	726.00	2.10	Water soluble	−6.19

--- No data available. ^a Data reported for LiOH H₂O.

), most of them being highly water-soluble [9].

In recent decades, the economic importance of Li has increased, with the supply reaching up to 500,000 Mg per year worldwide. Currently, there are no specific data on its release into the environment, but it can occur either in electronic waste or in pharmaceutical waste; both increase in concentration day by day, since there is still no economically efficient recycling of Li [11].

Li is present in various organisms, and although it is not an essential element in higher plants, it can have beneficial effects when applied in small quantities. In contrast, high levels of Li can damage the growth of roots and shoots, as well as alter photosynthetic activity and nutrient absorption [2,12]. Since its effects are controversial, there is a serious need to study the toxic levels and tolerance mechanisms that Li can cause in order to foster its proper use in plant species either in biostimulation or agronomic biofortification approached [7,12].

Lithium has low toxicity and does not accumulate in humans, since it is eliminated 24 h after ingestion. This represents a great advantage in future agronomic biofortification studies and for the pharmaceutical industry, where it is already used in the treatment of psychiatric disorders [8,9].

2. Abundance and Concentrations in the Environment

In the Earth’s crust, Li is ranked 27th in abundance [9,13]. It is not found as a free element, but rather in variable quantities in minerals such as silicates [spodumene (LiAlSi₂O₆), petalite (LiAl(Si₄O₁₀)), and eucryptite (LiAlSiO₄)]; micas [lepidolite (K(Li,Al)₃(Si,Al)₄O₁₀(F,OH)₂) and zinnwaldite (KLiFe²⁺Al(AlSi₃)O₁₀(OH,F)₂)]; and phosphates [amblygonite (LiAlFPO₄)]. In addition, it is present in surface water, groundwater, and seawater [4,14,15].

The total world production of Li in 2020 was 82,000 Mg [16]. The global reserve of Li is estimated to be equivalent to 29.8 million Mg [17]. The main producers are Chile, Argentina, China, Bolivia, Australia, the United States, and Russia [4,6,18].

Lithium is naturally found in water and soil; its concentrations on the planet are varied and depend on the nature of the rocks and minerals present. However, anthropogenic sources such as smelting and mining release significant amounts of Li into the environment [19]. The average concentration in surface water ranges from 1 to 10 µg L⁻¹, in seawater it is 0.18 mg L⁻¹, and in groundwater it is 0.5 mg L⁻¹ [17], although higher concentrations have been reported in some specific regions. For example, in Texas (USA), 170 mg Li L⁻¹ is reached, while in rivers in Chile the reported amounts range from 1508 to 5170 mg Li L⁻¹. In drinking water there is no standard level of Li that determines its quality for human consumption [7].

In Australia, Li is considered an environmental contaminant present in irrigation water and treated wastewater, which can be a source of toxicity for agricultural production; therefore, its levels should not exceed 2.5 mg L⁻¹ [20,21].

Lithium is present in all soils, and its concentration varies according to the type and mineral composition. Its average content in igneous rocks ranges from 40 to 45 mg kg⁻¹, while in sedimentary rocks its concentration is between 60 and 75 mg kg⁻¹ [8]. In addition, Li is found mainly in the clay fraction and to a lesser extent in the organic fraction of soil, between 7 and 200 µg g⁻¹, respectively [17]. Due to mineral degradation, Li ions are leached into the soil through rainfall, reaching water supplies [5], and because Li salts are water-soluble, the element can be easily absorbed by plants [20].

3. Uses of and Demand for Li

In industry, Li is used to produce alloys, lubricating greases, air conditioning systems, and electrical appliances [5,17]. In the last decade, new applications have been found, mainly in the manufacture of high-performance rechargeable batteries, portable electrical appliances, and high-strength light alloys for aircraft parts; as a carbon dioxide absorbent in spacecraft; in high-energy additives for rocket propellants; as a fusion fuel in hydrogen bombs; and as an energy storage device in electric and hybrid vehicles [6,17].

Lithium is not an essential element for plants and animals; however, Li carbonate, acetate, and citrate are used as medicine in the treatment of patients with psychiatric disorders [6,8,22]. According to the United States Environmental Protection Agency (U.S. EPA), the daily intake of Li in a 70 kg adult ranges from 650 to 3100 µg, acquired mainly through dietary sources consisting of grains and vegetables (430 to 2990 µg), dairy products (222 µg), and meat (2.5 µg) [7].

Given its high demand in modern technology, Li is considered “the white gold” [16]. Since 2010, the demand for Li has tripled (100,000 Mg year⁻¹) due to the mass production of rechargeable Li-ion batteries; forecasts suggest that it will peak in 2041 and slowly decline as the resource is depleted at the end of this century [23].

The consumption projection for the coming decades and the low recycling rate imply an increase in waste containing Li, mainly batteries, which will reach open landfills, aquatic environments, and agricultural fields, where they can have an impact on living beings and ecosystems. Knowing the effects that Li compounds produce in plant metabolism is essential to understand their impact on the growth, yield, and quality of crop plants [16,23].

4. Lithium Absorption, Transport, Sequestration, and Translocation in Plants

Lithium absorption and accumulation is different among plant species. There are plants that are bioaccumulators or hyperaccumulators of Li [24]. The Asteraceae and Solanaceae families and the halophyte group are Li accumulators, while citrus plants are sensitive to this metal [9,25]. The species Brassica napus and B. oleracea accumulate up to 2590 and 3091 mg Li kg⁻¹, respectively, making them excellent candidates for agromining and remediation studies [26].

In soil, Li has a weak sorption chemistry compared to other metals, but it increases with increasing pH. Its high affinity for clays is due to isomorphic substitution of Al³⁺ in the octahedral layer by Mg²⁺, which gives rise to a free position that Li⁺ can occupy. Li⁺ ions are selectively absorbed over other cations apparently in a non-exchangeable manner. Moreover, Li concentrations have been found to be proportional to those of Mg, probably due to their similarity in ionic radius [8,17] (Figure 1).

Furthermore, Li shares the same transporter as the K⁺ ion, and so it is easily translocated to the aboveground part. Because of this, the highest concentration of Li has been reported in leaf tissues compared to roots and bulbs [27,28].

As a mobile element, Li is easily absorbed by plants, although other factors including concentration, species, and genotype play a main role in absorption. In addition, the structure of the roots plays a pivotal role in the process [20].

The exact mechanism of Li⁺ absorption in plants has not been established, although two absorption and transport hypotheses have been proposed. In the first one, Li⁺ uptake occurs via symplast through passive transport, using transporters of cations such as Na⁺, K⁺, and Ca²⁺ (entry into the endodermis of root ciliated cells crossing from cell to cell through plasmodesmata until passing through the Caspary band and entering the xylem). In the second one, Li enters through the apoplast of the cells, but when blocked by the Caspary band it must be incorporated into the symplast in order to reach the xylem. This process may be a tolerance mechanism to relieve stress and keep Li⁺ retained in the apoplast (Figure 2) [19].

Several putative Li transporters are known, such as High-affinity Potassium Transporters (i.e., HKTs); Low-affinity Cation Transporters (i.e., LCT1); and Non-Selective Cation Channels (i.e., NSCC), which play an important role in allowing Li to enter root cells and accumulate in the cytosol. In addition, HKTs transport Li⁺ into the xylem, where Li+ follows the water flow to reach shoots and leaves (Figure 3) [8,19]. In the phloem, few ions enter, and some remain immobile, whereas others return to the root; in plants treated with high Li doses, it accumulates mainly in the vacuoles and in the cell wall [29,30,31] (Figure 2). The use of these transporters is related to the ionic radius of Li⁺ similar to other ions of essential elements as shown in Figure 1.

The translocation of Li and immobilization occur in plant leaves [32], and positive (stimulatory), neutral, or negative (inhibitory) responses may differ among species [25]. Li toxicity will depend on the concentration, exposure time, and age of the plant; however, there are still few studies on phytotoxicity, absorption, and accumulation of Li [20].

The sequestration of Li in cell organelles is the main adaptation and response strategy to stress in plants. In this sense, vacuoles are the site of Li compartmentalization. This was observed in the accumulator bluish dogbane (Apocynum venetum), which is capable of storing 72% of Li in vacuoles [30].

According to Tanveer et al. [19], in wheat (Triticum aestivum) plants, Li is not transferred to young organs, but rather accumulates in adult leaves. This agrees with Kent [33], who observed that young plants accumulate Li in the roots during the first few days, but as the exposure time increases, Li accumulates in older leaves, where in addition to remaining immobile, the net water gain during growth decreases.

5. Li in Plant Metabolism and Physiology

In plants, we have 17 essential elements for optimal growth. Other elements such as the beneficial ones are useful at low concentrations; however, when optimal levels are exceeded, crop development and yield can be altered [19,34].

Various authors consider that Li can have beneficial effects at low concentrations and toxic effects at high doses [28,35]. Although it has been established that it is not necessary for growth, stimulating results have been observed in physiological development in plants such as maize (Zea mays), wheat, and barley (Hordeum vulgare) [36].

In Arabidopsis thaliana, Li is a potent inducer of 1-aminocyclopropane-1-carboxylate synthase (ACC synthase), an enzyme that catalyzes the synthesis of 1-aminocyclopropane-1-carboxylate (ACC), a precursor molecule of ethylene formed from S-adenosyl methionine (SAM) [37]. Likewise, Li also stimulates the transcriptional expression of the SAM and pathogenesis-related proteins (PR) genes [18]. Additionally, in tobacco plants (Nicotiana tabacum) treated with Li⁺, accumulation of ethylene, salicylic acid, and gentisic acid was recorded; additionally, the expression of PR genes (PR-P, PR1, and PR5) was induced. This suggests that Li triggers a hypersensitive response to ethylene signaling [38]. The above is evidence that Li has toxic effects leading to senescence processes in higher plants. However, lithium can stimulate seed germination under dark conditions by inducing ethylene synthesis [39].

On the other hand, in humans and rats, polyamines (PAs) or biogenic amides have been shown to modulate neurotransmission and are responsible for the PA-mediated stress response (PSR) [40]. Lithium does not directly interfere with the activity of PAs-metabolizing enzymes; rather, it acts on the intact cell and interferes with stress-activated transduction pathways that converge to activate the PSR, probably at transcriptional or posttranscriptional levels, but may also be involved in posttranslational changes [41]. In higher plants, PAs regulate various physiological processes such as floral development, embryogenesis, organogenesis, fruit maturation and development, senescence, and responses to abiotic and biotic stress factors [42]. However, no effect of Li on the biosynthesis and metabolism of PAs has been shown in plants so far.

Lithium has been demonstrated to have a primary role in the metabolism of halophytic plants [9,18]. Li is absorbed by all plants, and low levels of Li stimulate many physiological parameters, such as biomass production, growth, yield, and maturation. In addition, Li has positive effects on processes such as photosynthesis, sugar translocation, enzymes, N metabolism, and disease resistance (Figure 4) [43].

Among the beneficial responses, Li can stimulate enzymatic activity by having a role as a cofactor. It has been proven that Li has an affinity with enzymes activated by Ca²⁺ and Mg²⁺ [25,43], though the specific function of Li⁺ ions in the process has not yet been established.

In maize, doses in the range of 1 to 64 mg Li dm⁻³ have stimulating effects [20]. In lettuce (Lactuca sativa), concentrations of Li₂SO₄ and LiOH between 7.5 and 22 mg dm⁻³ significantly increase root dry weight, specific leaf area, and stem diameter of plants [43]. In spinach (Spinacia oleracea) and mustard (Brassica juncea) plants grown in two soils, the addition of 40 mg Li₂SO₄ kg⁻¹ showed that light soil texture and low light intensity enhanced Li uptake, resulting in increases in total fresh plant weight and dry leaf weight, as well as increases in foliar concentrations of K, Fe, Zn, and S in spinach; by contrast, in mustard, increases only in the S concentration were recorded [44].

However, the detailed molecular mechanisms whereby Li affects plant biology remain largely unknown. In Paracentrotus lividus embryos, the exposure to 30 mM LiCl for 24 or 48 h differentially affected the expression of genes related to development, either involved in signaling or transcriptional regulation [45]. Concentrations of Li ranging from 25 to 50 mg L⁻¹ may increase plant growth and biomass but mechanisms underlying cis- or trans-regulatory variations remain poorly understood [46]. In Apocynum pictum, the application of 25 mmol LiCl L⁻¹ increased germination percentage [47], which may be attributed to a possible effect on the mitotic cycle of cells [24]. Interestingly, more negative responses are reported in hydroponic media than with soil or foliar applications [46].

6. Phytotoxic Effects of Li

The toxic effects of Li on plats were first reported in 1871, when Li was found to cause death in wheat plants and reduction in biomass in rye (Secale cereale) [36]. High levels of Li are toxic to plants and can cause chlorosis, necrotic lesions, and leaf curl (Figure 4) [9,38].

Excess Li can inhibit rhythmic plant movement, pollen germination, root growth, and gravitropic response, and affect microtubule dephosphorylation [9]. Furthermore, exposure to 5 mM LiNO₃ affects the development and germination of tobacco microspores [25,38]. Its teratogenic effects are attributed to the alteration of Ca²⁺ mobilization in the plasma membrane [48].

Doses higher than 10 mg Li L⁻¹ in cotton (Gossypium hirsutum) cv. Siokra, and 16 mg Li L⁻¹ in maize cv. Terrific caused growth retardation and toxic effects such as chlorosis and necrotic spots [49], symptoms that have also been observed in avocado (Perea americana) plants treated with 16 mg Li L⁻¹ [50]. In maize, chlorosis, necrosis, and browning of leaves as well as thickening and shortening of the main root have also been reported when 64, 128, and 256 mg Li dm⁻³ were added to the nutrient solution [20].

In sunflower (Helianthus annuus), toxic effects have also been reported when 50 mg Li dm⁻³ was applied [9]. Cotton and red beet (Beta vulgaris) are more tolerant to Li compared to citrus plants such as sour orange (Citrus × aurantium), in which Li causes necrosis, chlorosis, and leaf abscission [50]. These same symptoms were found in tobacco when 50 mM LiCl was applied [38].

In common bean (Phaseolus vulgaris) cv. Blue Lake 290, the application of doses between 8 and 12 mg LiNO₃ kg⁻¹ caused marginal chlorosis, decreased leaf area, and fresh and dry weights of leaves, stems, and roots. These same concentrations increased stomatal diffusion causing partial stomatal closure (Figure 4), suggesting that Li affects plant-water relations [51].

In onion (Allium cepa), the application of 100 mg Li L⁻¹ decreased the germination rate of bulbs and root length of seedlings [24]. In green amaranth (Amaranthus viridis), the application of 25 to 100 mg Li₂SO₄ L⁻¹ reduced the average germination, speed of germination, speed of accumulated germination, coefficient of rate of germination, and germination percentage of seed [32].

In cabbage (Brassica oleracea var. capitata), the application of 1 meq Li L⁻¹ (6.94 mg Li L⁻¹) and 10 meq Li L⁻¹ (69.41 mg Li L⁻¹) decreased the total dry weight by 50%; once absorbed by the plant, Li was mainly translocated to the outer leaves [52].

Li compounds produce differential effects on plants (

Table 2. Beneficial and toxic effects of lithium (Li) compounds on different plant species.

Plant	Concentration	Effects	References
Cabbage (Brassica oleracea var. capitata L.) cv. Nagaoka	1 and 10 meq Li L−1	Total dry weight decreased by 50%	[52]
Common bean (Phaseolus vulgaris L.) Bush Blue Lake 290	4 mg LiNO3 kg−1 >4 mg LiNO3 kg−1	Increases in plant height, fresh weight, and leaf area. Partial closure of stomata and an effect on water relations	[51]
Radish (Raphanus sativus L.)	1 mM LiNO3 2 mM LiNO3	Increase in dry weight of leaves and bulb Reduction in dry weight of leaves and bulb	[53]
Lettuce (Lactuca sativa L.)	1–2 mM LiNO3	Significant increase in dry weight of leaves	[53]
Watercress (Nasturtium officinale L.)	1 mM LiNO3	Significant increase in dry weight of leaves	[53]
Tobacco (Nicotiana tabacum L.)	50 mM LiCl	Growth inhibition and leaf necrosis	[38]
Spinach (Spinacia oleracea) cv. Samich	40 mg Li2SO4 kg−1	Increase in biomass	[44]
Mustard greens (Brassica juncea) cv. Florida Broadleaf	40 mg Li2SO4 kg−1	Increase in biomass	[44]
Abyssinian mustard (Brassica carinata)	0.03–0.3 mM LiCl 30–120 mM LiCl	Increase in radicle length at germination and fresh weight Reduces germination rate, fresh weight, and chlorophyll concentration Increases anthocyanins	[54]
Sunflower (Helianthus annuus L.)	50 mg LiCl dm−3	Necrosis in leaves, reduction of dry biomass in shoots and leaf area Increased levels of lipid peroxidation	[9]
Maize (Zea mays L.) var. saccharata Kcke, cv. Zlota Karlowa	50 mg LiCl dm−3 5 mg LiCl dm−3	Necrosis in leaves, reduction in dry biomass, decrease in photosynthetic pigment content, and increase in lipid peroxidation levels Increased aboveground biomass and leaf area	[9]
Lettuce (Lactuca sativa L.) var. capitata cv. Justyna	100 mg LiOH or LiCl dm−3 50 mg LiOH dm−3 2.5 mg LiOH dm−3	Necrosis, inhibition of growth and yield Reduction in fresh weight of shoots and roots Increased fresh root weight	[25]
Sunflower (Helianthus annuus L.)	0.2, 0.5, 5, 10, 60, and 80 mM LiCl	Reduction in hypocotyl length	[55]
Kendyr (Apocynum pictum Schrenk)	25 mmol LiCl 100–400 mmol LiCl 200–400 mmol LiCl	Increased seed germination percentage Decrease in germination rate and percentage Reduction in dry weight of leaves, stems, and roots Decrease in chlorophyll a and b and carotene content	[47]
Lettuce (Lactuca sativa L.)	7.5 to 22 mg Li2SO4 or LiOH dm−3 40 mg Li2SO4 dm−3	Increases dry root weight, specific leaf area, and stem diameter Reduced stem diameter, root dry weight, total leaf area, plant height, and leaf dry weight	[43]
Onion (Allium cepa L.)	100 mg Li2SO4 L−1	Decreased germination rate and root length	[24]

). For example, when applying concentrations less than 50 mg LiCl L⁻¹ in bluish dogbane (Amsonia tabernaemontana), Li negatively affected growth, germination, and root biomass, while the same concentration of LiNO₃ affected only shoot biomass. Furthermore, concentrations between 50 and 500 mg L⁻¹ of both sources reduced the content of chlorophylls a and b by 50% [16].

7. Interaction of Li with Other Elements, Nutrients, and Biomolecules

Li shows high affinity and similarity enabling it to replace essential elements such as K⁺, Ca²⁺, and Mg²⁺ (Figure 1) [19,50], which represents a route of entry into plant cells by binding to sites not occupied by these elements [6]. Concentrations of 50 to 100 µg Li dm⁻³ in irrigation water alter the processes of absorption and distribution of essential elements in plants [20].

In plants, Li⁺ ions can alter biochemical processes through interaction with proteins and through modification of gene expression [19]. The best-known example is its relationship with the inositol triphosphate second messenger system, where Li⁺ is a non-competitive, rapid, and reversible inhibitor of the enzyme myo-inositol-1-phosphatase (IMP or IMPase), which participates in the recycling rate of the inositol second messenger and in the hydrolysis of myo-inositol phosphate. Li⁺ reduces the hydrolysis rate of myo-inositol-1-phosphate without altering the binding of the substrate or the Mg²⁺ ion to the IMPase according to research studies with animal systems [18,30].

Although the mechanism of action of Li in plants has not yet been established, the most accepted hypothesis is “inositol depletion”, since inositol monophosphatases are sensitive to Li⁺ ions, which causes a reduction in cellular inositol levels and inhibits the inositol cycle and Ca signaling [9,13,38].

In roots, the absorption interaction between Ca²⁺ and Li⁺ is so competitive or antagonistic that Ca²⁺ can inhibit Li⁺ absorption [56]. Ca²⁺ has the ability to prevent the toxicity and absorption of lighter minerals such as Li⁺, which has been observed in oat (Avena sativa), fodder beet (Beta vulgaris subsp. vulgaris), and Brassica juncea plants [8,19].

As previously indicated, Li can affect proteins of the 1-aminocyclopropane-1-carboxylate synthase (ACC synthase) family, which catalyzes the synthesis of ACC from S-adenosyl methionine (SAM), a precursor for the synthesis of the ethylene hormone [37].

The oxidative damage to the photosynthetic apparatus and the alteration of chlorophyll content caused by Li are due to the increased catalytic action of the enzymes chlorophyllase, pheophorbide a oxygenase (PHO), red chlorophyll catabolite (RCC) reductase (RCCR), and Mg-dechelatase, which are responsible for chlorophyll bleaching [19].

In sorghum plants (Sorghum vulgare) var. Tamaran, Li did not affect the photosynthetic processes, changing neither the rate of transpiration nor intercellular CO₂ concentration in young leaves. However, the activity of the enzymes phosphoenolpyruvate carboxykinase (PEPCK) and phosphoenolpyruvate carboxylase (PEPCase), and the phosphorylation status of plants treated with 10 mM LiCl decreased [57].

8. Ranges of Tolerance, Cytotoxicity, and Genotoxicity of Li

The presence of high concentrations of Li⁺ can induce the formation of free radicals and oxidative stress in cells, which can damage macromolecules such as DNA, lipids, and proteins, and disrupt biochemical and physiological pathways that can limit plant growth [18,24].

The presence of Li₂CO₃ in onion meristematic roots decreased the mitotic index (MI) by 8.2, 19.4, and 38% with the application of 25, 50, and 100 mg Li₂CO₃ L⁻¹ compared to the control, which is indicative of a delay in the mitotic division process [24].

Regarding the genotoxic effects of Li⁺, chromosomal abnormalities such as bridges, sticky chromosomes, fragments, uneven chromatin distribution, wandering chromosomes, reverse polarization, irregular mitosis, and multipolar anaphase were found when applying 25 to 20 mg Li L⁻¹ [24]. Though Li has not been reported as a potent mutagenic agent [18], in onion cells the presence of DNA fragments increases as the concentration increases from 25 to 20 mg Li₂CO₃ L⁻¹. In addition, the affinity of Li⁺ for DNA is due to the molecular coupling and interaction it has with the nitrogenous bases of DNA [24].

As a result of a meta-analysis of the existing recent literature investigating the impact of Li sources and levels on plant species under different growth conditions [46], it was concluded that the toxic effects of Li vary with Li source materials, with LiCl affecting germination and root biomass to a greater extent, while LiNO₃ has more negative effects on shoot biomass. Lithium concentrations <50 mg L⁻¹ influences physiological indicators, while 50–500 mg L⁻¹ Li concentrations influence biochemical parameters. The dose-response relationship (EC₅₀) values regarding the exposure medium of Li sources in plant species were ranges 24.6–196.7 mg kg⁻¹. The uptake potential of Li is dose-dependent, and its translocation/bioaccumulation remains unknown. The toxic effects of Li exposure in plants vary as a function of medium, and, interestingly, more negative responses are reported in hydroponic systems than with soil or foliar applications.

9. Treatment with and Intake of Li in Humans

In animals and humans, Li is biologically important in various physiological processes, and although its mechanisms of action are not established, they are related to the functioning of some enzymes, hormones, vitamins, and growth factors [13,19,58].

In the medical field, it has been established that the use of small amounts of Li can have beneficial effects on human health, since this element has the therapeutic advantage of not being cumulative for humans and being even less toxic than beneficial elements, such as Zn [31,59]. Lithium is mostly supplied as Li₂CO₃ in psychiatry; however, it is also used in the forms of citrate, acetate, glutamate, nitrate, orotate, and sulfate as a treatment for bipolar disorder, depression, manic episodes, suicide risk, and schizophrenia [60,61,62].

Therapeutic doses of Li are different among authors. For instance, Jefferson and Greist [60] suggest doses of 1200 and 2100 mg Li₂CO₃ day⁻¹, while Marshall [59] and Calabrese et al. [62] consider ranges from 600 to 1200 mg day⁻¹ of Li₂CO₃ (113 to 226 mg of Li), and for LiC₅H₃N₂O₄ H₂O (Li orotate) it is 120 mg per day (3.83 mg of Li). However, lower doses, even compared to those found naturally in foods, can be effective [61].

Li aspartate and Li orotate are the most widely available drugs due to their low-dose presentation and easy absorption. On the other hand, Li carbonate and Li citrate are easily ionized, causing them to be less diffuse when entering the cell [59]. This had been observed in a comparative study between Li orotate and Li carbonate in rats, where it was found that Li orotate is absorbed three times more than Li carbonate in the brain [63].

Daily Li intake figures for a 70 kg adult vary, with the EPA recommending between 650 and 3100 µg Li day⁻¹ [8], others suggesting 1000 µg day⁻¹, equivalent to 14.3 µg kg⁻¹ of body weight [58,59,61], and 5 to 20 µg day⁻¹ [62]. Recommended doses and daily intake limits in humans may vary in different regions of the world; Figure 5 shows an overview of what is reported in the literature. Lithium carbonate is used in psychiatry in doses close to the maximum permitted intake level. The target organ of Li toxicity is the central nervous system; therefore, it is used therapeutically to act on membrane transport proteins in the treatment of manic depression. In rats, the lethal dose of LiCl ranges between 526 and 840 mg per kg body weight. In humans, 5 g of LiCl can cause fatal poisoning. Blood concentrations of 10 mg Li L⁻¹ result in slight intoxication in humans; increases to 15 mg Li L⁻¹ cause speech disorders. Concentrations of 20 mg Li L-1 in blood may increase the risk of death [14].

In Chile, where lithium-rich salt flats can contain up to 1500 mg Li L⁻¹, total lithium intake can reach 10 mg per day with no evidence of adverse effects for the local population. The minimum physiological lithium requirement of a human adult is less than 0.1 mg per day [14].

10. The Future of Li in Agriculture and Animal Production

In the agrifood area, the idea of biofortifying crops with Li has emerged [31] In fact, the nutritional benefits that Li can bring to the diet are promising, mainly in cereals; vegetables such as potato (Solanum tuberosum), cabbage, and tomato (Solanum lycopersicum); and mushrooms, where quality and yields would not be compromised [8,58].

Naturally, foods such as cocoa (Theobroma cacao), oats, seafood, algae, goji berries (Lycium barbarum), and egg yolks are important sources of Li and are considered “neurotonic” for their nutritional effects on the brain and central nervous system [59].

There are also studies on Li biofortification in poultry. In turkeys supplemented with 0.05, 0.10, and 0.15 mg Li kg⁻¹ for 70 days, an increase in weight was observed, as well as an increase in the concentration of this element in the thigh, breast, and liver compared to control turkeys that did not receive Li [64].

In marine ecosystems, strong variations in Li are observed among organs, in line with the biochemical similarity between this element and Na during transport in the brain and in the osmoregulatory organs. The gills and kidneys of fish have high concentrations of Li (0.26 and 0.15 μg Li g⁻¹, respectively). In contrast, low concentrations of Li (0.07 and 0.06 μg Li g⁻¹, respectively) are found in fish liver and muscle [65]. These types of studies are fundamental for the use of Li in ocean farming and in other fish production systems based on aquaculture and the use of artificial reefs.

Given that the projected global food demand for 2050 proposes a healthy diet, the interest in nutrients that meet the needs to avoid diseases caused by the lack of elements such as Li deserves special attention [31], and there is still research to be performed on this topic. Recently, Li fortification was studied in five grape varieties (Vitis vinifera) using an organic fertilizer rich in Li (0.28 g L⁻¹), where it was found that foliar supplementation of this element improves nutrient absorption and promotes the content of phenolic compounds, mainly in the skin of grapes, an important characteristic for wine production [66].

The excessive use of Li compounds in recent decades suggests that future generations will have higher consumption patterns and, consequently, the excessive presence of Li-based waste, which can produce excessive concentrations in soils and water bodies intended for agricultural use; therefore, it is necessary to carry out studies in plants that allow an understanding of the effects at different physiological stages and in different species, mainly those used for human consumption [32].

11. Conclusions

The processes of absorption and accumulation of lithium in plants are affected by different factors including the concentration of the ion in the growth medium, the chemical form, the species of plant, the age of the plant itself, and the method of application, among others. The beneficial or toxic results that Li can cause in plants depend on the concentration, exposure time, species, and genotype. Positive effects of Li in plants when applied at low concentrations (in the range of 24 to 196 mg L⁻¹) suggests that this element can be successfully used in biostimulation and biofortification approaches, which, in the end, may benefit both plant and human health.