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Research Article | DOI: https://doi.org/10.31579/2692-9422/009
1Naturveda SAS, ZAC de Lavaur 63500 Issoire, France.
2Hydroxydase SAS, 11 Allée de la source 63340 Le-Breuil-sur-Couze, France.
3Polytrap Pharma, 122 Pricanko colony, Indore (MP), India.
*Corresponding Author: Ravi Shrivastava, Naturveda SAS, ZAC de Lavaur 63500 Issoire, France.
Citation: Ravi Shrivastava, Nathalie maneby, Deepti shrivastava and Julien Bonnefo, (2025), Can Bipolar Disorders be Treated by Stimulating Neurite Growth with Hydroxydase lithium and Magnesium Rich Water?, J. Neurodegeneration and Neurorehabilitation, 4(1); DOI: 10.31579/2692-9422/009
Copyright: © 2025, Ravi Shrivastava. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 10 June 2025 | Accepted: 14 July 2025 | Published: 22 July 2025
Keywords: neuronal cell; hydroxydase; neurite sprouting; neurite length; lithium; magnesium; depression; bipolar disorders
Background/Aim: Bipolar (BD) and depressive disorders (DD) are common psychiatric conditions marked by reduced neuronal cells and impaired neurite growth, leading to disrupted neuronal connectivity and symptoms characteristic of BD or DD. Current treatments poorly address neuronal damage. First-line treatments like lithium (Li) stabilize mood swings but high doses cause side effects. Magnesium (Mg), through a distinct mechanism, partially stabilizes mood. Studies on synergistic effects of Li and Mg are scarce. We evaluated the neurite growth properties of one of the richest source of bioavailable lithium (9737 µg/L) and magnesium (243 mg/L) on the growth of neurones and neurites in vitro.
Materials and Methods: Commercially available rat cortical neurone cultures were exposed on day 1 to 1%, 3%, 5% Hydroxydase water, or to the same volumes of Li-carbonate solution (20 µg/mL) as positive control, or culture medium containing no lithium as negative control. Number of neurites per cell and mean neurite length were analysed on days 1, 3, and 7 using microscopic imaging.
Results: The test substances showed no cytotoxic effects. Li-carbonate had no significant effect on neuronal growth, neurite number or length. Hydroxydase water increased neuronal cell numbers (+11.54%) and enhanced neurite growth (+37%) and elongation (+47%) per cell by day 7. These effects were observed across all concentrations and began as early as day 1.
Conclusion: Hydroxydase water significantly enhances neuronal differentiation, neurite sprouting, and elongation, suggesting improved neuronal connectivity and neurotransmission in vivo. The synergistic action of bioavailable Li+ and Mg2+ presents a natural and effective complement to synthetic drugs for BD and DD treatment.
BD : (bipolar Disorder)
DD : (Depressive disorder)
BDNF : (brain-derived neurotrophic factor)
HPA : (hypothalamic-pituitary-adrenal)
GABA : (Gamma-aminobutyric acid)
NMDA : (N-methyl-D-aspartate)
Bipolar disorders (BD) affect approximately 5% of the global population. Onset typically occurs in late adolescence or early adulthood, with equal prevalence among males and females. Acute or chronic depressive disorders (DD) concern 5-10% of the population, with onset frequently in the mid-twenties [1]
It has been clearly established that both BD and DD are associated with reduced neurogenesis, particularly in the hippocampus [2].The cause(s) and physiopathology of these diseases are not well understood, but chronic stress, specific traumatic events, and certain genetic factors are considered contributors that trigger neuronal degeneration and the disease [3].Reduced numbers of neurites in brain regions such as the prefrontal cortex and hippocampus, along with fewer neurites per neuron, shorter neurite length, and underdeveloped glial cells, are observed in BD and DD patients [4]. These neuronal changes contribute to impaired synaptic connectivity, poor neurotransmission, and, consequently, impaired brain functioning [5]. BD and DD also involve dysregulation of brain-derived neurotrophic factor (BDNF), which plays a key role in neuronal survival and synaptic plasticity [6]. Chronic inflammation, oxidative stress, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction further exacerbate these impairments, leading to disruptions in serotonin, dopamine, and glutamate neurotransmitters [7].
Understanding these neuronal changes has therapeutic implications. Interventions aim to enhance and stabilize neurotransmission, as well as promote neurogenesis and neurite outgrowth [8]. Antidepressants, mood stabilizers, and lifestyle modifications, such as exercise, help mitigate some cognitive and emotional deficits in BD and DD, but no specific treatment directly addressing neuronal damage is available [9,10].
The most used and effective treatment is Li, which stimulates BDNF production and improves synaptic plasticity. However, there is little evidence that Li promotes neuronal and neurite growth [11,12]. While neuroprotective properties of Li are recognized, its direct impact on neurite outgrowth is inconsistent, likely due to the difficulty of evaluating neuronal or neurite growth in BD patients. Similarly, magnesium (Mg) may help promote neuronal health and minimize BD symptoms akin to Li, but its use remains limited[13].
Li stabilizes mood and modulates neurotransmitter release through intracellular signalling pathways, including inositol monophosphate and glycogen synthase kinase-3β (GSK-3β), and enhances neurotrophic factor [removed]e.g., BDNF). While its neurogenic effects are modest and insufficient to fully reverse neuronal atrophy in BD and DD [14,15]. Other treatments, such as valproate, benzodiazepines, and antipsychotic drugs, primarily regulate neurotransmitters but do not address neuronal structural deficits [16]. Novel therapies targeting neurogenesis and neurite repair are under investigation, including neurotrophin mimetics and cytokine-based therapies [17,18].
Magnesium (Mg), involved in neurotransmitter regulation, synaptic plasticity, and neuroprotection, is emerging as a potential adjunctive therapy for BD and DD. Mg stabilizes glutamate and GABA levels, reduces oxidative stress, and minimizes neuronal inflammation[19]. Studies have shown low Mg levels correlate with increased depressive symptoms in BD patients, and supplementation enhances mood stabilizers’ efficacy [20,21]. It has been observed that Mg supplementation could be as effective as lithium in treating rapidly cycling bipolar patients[22].
As Li is also considered to reduce the frequency and severity of manic and depressive episodes in BD, while Mg supplementation helps stabilize mood by improving neurotransmission, combining Li with Mg in the treatment of bipolar disorder (BD) is now generating considerable interest due to their complementary mechanisms, which may enhance therapeutic outcomes [13,23]
Currently, Li and Mg are usually administered orally in solid dosage forms such as tablets which often results in suboptimal bioavailability, potentially limiting their therapeutic efficacy. Factors such as gastrointestinal pH and interactions with food can affect the absorption, leading to very low serum concentrations and necessitating careful monitoring to avoid toxicity. Secondly, the oral administration also leads to higher absorption of minerals when the tablet is disintegrated, leading to much higher serum concentrations for a very short period which may be toxic, followed by low pharmacologically inactive blood levels throughout the day [24]. Similarly, solid forms, especially those containing poorly soluble salts like oxides, sulphates, or chlorides, exhibit limited absorption due to competition with other ions in the gastrointestinal tract. Liquid preparations also contain these salts which are poorly absorbed.
In contrast, liquid formulations, particularly those containing Li+ and Mg2+ in ionic forms, may offer enhanced bioavailability. The immediate availability of ions in these solutions may facilitate more efficient absorption in the small intestine, potentially leading to more consistent therapeutic effects [25]. This improved absorption could allow for lower dosing, reducing the risk of side effects associated with higher doses of tablet forms and probably long-lasting therapeutically active serum levels throughout the treatment period.
Hydroxydase is the most Li+-rich water in the world (8-9 mg/L), equally containing as high as 243 mg/L Mg2+. Being a perfectly stabilized natural association of Li+ and Mg2+ in an ionized bioavailable form, our aim was to evaluate whether synergistic effects of these two elements could help grow neurons and neurites, a prerequisite for the treatment of BD and DD. To better quantify the effects of Hydroxydase, we used in vitro neuronal cell cultures [27] and compared the efficacy against Li-carbonate, the most common salt used in solid tablets.
The objectives were to check whether a naturally stabilized, bioavailable, and ionized form of Li+ and Mg2+which can be easily and rapidly absorbed and used by the neuronal cells, could help neuronal cell growth as well as stimulate the growth and the length of the neurites, the basic requirements for an effective treatment of BD /DDs.
Test products: Cell culture medium containing 1% serum was used for cell controls and for test product dilutions. All test products were added in the culture medium at a volume not exceeding 5% total culture medium volume. Li-carbonate stock concentrations were prepared by dissolving 2.0 mg Li-carbonate salt in 10 ml (200 µg/ml) culture medium. The concentration used for experiment assumed that for a human of 70 kg, 600 to1200 mg of Li-carbonate is usually administered as daily dose, equivalent to 8 to 16 mg/kg (8-16 µg/g). These doses maintain a blood concentration of about 22-45 Mg/L (0.6 – 1.2 mEq/L or 22 to 45 µg/ml) [27,28]. For in vitro testing, we prepared culture mediums containing 20 µg/ml (1%), 60 µg/ml (3%) and 100µg/ml (5%) representing mean to double concentrations of Li carbonate to which neuronal cells are likely to be exposed during Li therapy.
Hydroxydase water containing 9737µg/L Li+ and 243 mg/L Mg2+ was used in 200 ml, no air contact filled glass bottles. Hydroxydase water was used unchanged at 1%, 3%, and 5% concentrations in the culture medium. Each experiment was performed in triplicate and repeated at least twice. Mean values of minimum 6 tests were then calculated[29].
Cell cultures: Commercially available cryopreserved rat cortical neurons were purchased (A10008041, Invitrogen) and were cultured as per the suppliers’ recommendations using a slightly modified method as described by Facci et al [30]. In short, cells were quickly thawed by gently spinning in a 37°C water bath for about 1–2 minutes and then transferred to a 50 mL sterile tube. 20 mL of warmed culture medium (neurobasal medium, containing 2mM L-glutamine, antibiotics and 4% foetal bovine serum), was added to the cell-containing tube. 100 μl of medium containing 103 cells /ml density was introduced in each of the 12-wells of culture plate (Corning) coated with poly-D-lysine and laminin. Cells were then incubated in a 37° C humidified incubator with 5% CO2 for at least 1h to allow cell attachment. The culture medium was then replaced by 1ml culture medium containing 1% serum and desired concentrations (1%, 3%, or 5%) of the test products in the culture medium. Each experiment was repeated at least thrice.
Image analyses: Cell cultures were imaged after 1, 3, and 7 days of culture as described by M. Pool et al [26]. On days 1 and 3, images of each plate were taken with an inverted microscope, making sure to keep the settings constant between images. The culture dishes were returned to the incubation chamber until final image analyses and fixation on day 7.
Neuronal cell count and neurite growth measurements: During the initial step, we used standard microscope image analyses to determine cell number, neurite branches originating for the cells, and neurite length as described by Rønn et al [31]. The mean number of neuronal cells was quantified by counting total number of neurons in a fixed area of the photo for all the 3 images per dilution at each time point. The total neurite length per cell was estimated by counting the number of intersections between neurites using conventional computer-assisted microscopy to measure the length. The absolute length of neurites per cell was subsequently estimated from the number of neurite intersections per cell.
These data obtained through conventional image tracing method were further confirmed through freely available Fiji ImageJ package, including the NeuronJ plugin for neurite tracer analysis [32]. The plugin analyses fluorescence microscopy image processor measures number of cells / area, the neurite outgrowths, and the neurite length of each neuron visible in the defined area of cell culture image. The results are presented as mean number of cells, number of neurites, and length of neurites (µm) in minimum 2 cultures (n=6). The length of neurite(s) in each cell was measured for all the cells present in the observation field, added, and mean value per cell (µm) was determined.
Statistical analysis: Student t test was used to compare the mean and ± SD of the mean between negative cell cultures treated with culture medium and Hydroxydase or lithium carbonate treated groups. One way ANOVA was used to compare the differences between controls and Hydroxydase.
On day 7, in Hydroxydase-treated cell cultures, a total of 22 cells are visible while other cells are not attached to the surface. The cells have neurites but not clearly visible. After NeuronJ processing, the neurite growth of each cell is clearly visible and can be measured.
The images in Figure 1 and 2 are provided as an example to illustrate the technique used as well as the parameters measured in this study. The images in Figure. 1 and Figure. 2 are from Madeline pool et al. [26].
Figure 1: Phase contrast image before (A) and after (B) preparation in ImageJ. The neurites in (B) are much more visible and clearer to calculate the number of cells and neurite growth. Bar = 50μm.
All the images in Figure. 2 represent the same cell culture. The 1st image (Figure. 2-A) represents neuron cell culture observed under the phase contrast microscope, the same culture in image analysis (Figure. 2-B) and under neurite tracer (Figure. 2-C). The colour of the trace in Fig. 2-C indicates whether the neurites are originated from the soma (primary neurite, tracing in red arrows), or a secondary neurite (tracing in blue arrows).
All neurites, whether primary or secondary, are considered as individual neurons and the total length of all the neurites originating from a neuron was measured. The data obtained by counting neurite intersections correlated statistically with results obtained using conventional microscopic image tracing and through Neurite Tracer, a neurite tracing plugin program.
Neuron observations on days 1, 3, and 7 for the three test product concentrations: The results are shown in Table 1.
| Concentration exposed | Day after treatment | Mean N° of cells (n=3) | Mean N° of neurites/cell (n=3) | Mean length of neurites µm (n=3) |
| Group 1: Culture medium % | ||||
| 1.0% | Day 1 | 14,2 | 12.32 ± 0.21 | 169.25 ± 18.36 |
| Day 3 | 16,6 | 14.51 ± 0.41 | 145.65 ± 23.40 | |
| Day 7 | 16,1 | 12.55 ± 0.55 | 139.52 ± 31.64 | |
| 3.0 | Day 1 | 15,3 | 13.26 ± 0.60 | 178.15 ± 22.80 |
| Day 3 | 16,6 | 14.35 ± 0.74 | 156.28 ± 14.32 | |
| Day 7 | 15,4 | 16.41 ± 0.29 | 155.20 ± 27.70 | |
| 5.0% | Day 1 | 17,0 | 13.92 ± 0.15 | 183.08 ± 32.05 |
| Day 3 | 15,9 | 15.28 ± 0.55 | 174.08 ± 30.07 | |
| Day 7 | 16,2 | 16.15 ± 0.48 | 174.38 ± 19.37 | |
| Mean | 15.92 ± 0.85 | 14.30 ± 1.46 | 163.95 ± 15.30 | |
| Group 2: Lithium carbonate salt solution 20 µg/ml | ||||
| 1.0% | Day 1 | 13,6 | 13.44 ± 0.53 | 134.15 ± 31.34 |
| Day 3 | 15,5 | 14.10 ± 0.65 | 181.30 ± 18.31 | |
| Day 7 | 17,8 | 12.10 ± 0.37 | 157.39 ± 30.48 | |
| 3.0% | Day 1 | 16,2 | 14.15 ± 0.28 | 156.38 ± 34.39 |
| Day 3 | 17,7 | 13.95 ± 0.48 | 192.88 ± 27.28 | |
| Day 7 | 15,6 | 13.15 ± 0.82 | 175.66 ± 36.85 | |
| 5.0% | Day 1 | 16,7 | 15.11 ± 0.74 | 169.32 ± 41.25 |
| Day 3 | 17,3 | 14.26 ± 0.41 | 203.47 ± 29.18 | |
| Day 7 | 16,0 | 15.68 ± 0.35 | 184.36 ± 25.66 | |
| Mean | 16.26 ± 1.31 | 13.99 ± 1.04 | 172.76 ± 21.12 | |
| Group 3 : Hydroxydase water | ||||
| 1.0% | Day 1 | 14.4 | 15.32 ± 0.62 | 142.99 ± 64.6 |
| Day 3 | 17.5 | 16.30 ± 1.21 | 241.44 ± 72.00 | |
| Day 7 | 18.1 | 18.31 ± 0.87 | 279.50 ± 65.27 | |
| 3.0% | Day 1 | 15.6 | 15.68 ± 0.71 | 188.77 ± 59.34 |
| Day 3 | 20.9 | 19.14 ± 0.84 | 231.88 ± 94.44 | |
| Day 7 | 18.6 | 23.35 ± 0.45 | 346.63 ± 96.74 | |
| 5.0% | Day 1 | 16.1 | 16.36 ± 0.64 | 169.45 ± 84.31 |
| Day 3 | 20.1 | 21.10 ± 0.59 | 264.87 ± 105.81 | |
| Day 7 | 22.4 | 26.40 ± 1.26 | 375.08 ± 61.29 | |
| Mean | 18.19 ± 2.61 | 19.10 ± 3.829 | 248.96 ± 77.58 | |
Table 1: Effect of exposure of three different concentrations of either culture medium, Li-carbonate salt solution 20µg/ml or Hydroxydase Li+ + Mg2+ rich water on rat hippocampal neurons in vitro. The observations were made after 24h (Day 1), and on days 3 and 7 on the growth of neuron cells, as well as on the mean number of neurites and the mean neurite length (µm) per cell. The values represent observations in 3 cultures for total number of cells per well, the mean number of neurite outgrowth in the cells of a culture well and the total length of neurites in these cells (µm) ± SD of the means.
The results from this study highlight several important observations regarding the effects of Hydroxydase water compared to the culture medium and Li-carbonate salt solution 20µg/ml on neuronal growth parameters.
Cell culture controls: At the start of the study, the neuron cultures were nearly identical with respect to the number of neuronal cells, number of neurites per cell, and the neurite length. This indicates that the experimental conditions began with comparable baselines, ensuring the observed effects are attributed to the treatments. On day 0, when the cells were cultured, there were no neurites. This reinforces that all neurite growth observed during the study resulted from the treatments applied during the experimental period.
Effect on mean number of neuron cells: The mean number of cells with three different concentrations, in control cultures exposed only to the culture medium was 15.92±0.85 and 16.26±1.31 in the Li-carbonate control group, showing no significant difference between these two groups (Figure. 3). Cells treated with 1%, 3% or 5% Hydroxydase water, the number of cells was slightly higher compared to culture medium exposed controls and Li-carbonate group. While the difference is not statistically significant (18.19±2.61), it reflects the potential of Hydroxydase to support cell proliferation more effectively as well as absence of cytotoxic effects at all the test concentrations for the three test products.
Figure 3: Effect on mean number of neuronal cells in cell cultures exposed to 1%, 3%, and 5% concentrations of culture medium (white bars), Li-carbonate solution (grey bars) and to Hydroxydase water (black bars). The bars represent mean values observed on days 1, 3, and 7 for the three test product concentrations for each test liquid ± SD.
Number of neurites per Cell: Although Hydroxydase water had little effect on the growth of the number of cells compared to the controls, its effect on neurite formation was much more pronounced (Figure. 4). In the Hydroxydase group, the mean number of neurites was nearly up to 30% higher (19.10±3.8) compared to the culture medium (14.30±1.46) and the Li-carbonate group (13.99±1.04) This demonstrates that Hydroxydase significantly stimulates the generation of new neurites, indicating a strong effect on neuronal differentiation.
Figure 4: Effect on the mean number of neurites on day 1, 3, and 7 exposed to culture medium (white bars), Li-carbonate solution (grey bars) and to Hydroxydase water (black bars) ± SD of the mean. The bars represent mean values observed on days 1, 3, and 7 for the three test product concentrations for each test liquid ± SD.
Figure 5: Effect on the length of neurites in µm on day 1, 3, and 7, exposed to culture medium (white bars), to Li-carbonate solution (grey bars) and to Hydroxydase water (black bars) ± SD of the mean. The bars represent mean values observed on day 1, 3, and 7 for the three test product concentrations for each test liquid ± SD.
Effect on the mean length of neurites: Neurite growth started on Day 1 in all groups and progressed steadily up to Day 7 with all treatments showing gradual increases in neurite length. However, the mean growth of neurites was significantly faster in the Hydroxydase group (248.96±77.58). By the end of the study on day 7, the neurite length in the Hydroxydase group was nearly 47% higher compared to both the culture medium (163.95±15.30) and Li-carbonate group (172.76±21.12). This suggests that Hydroxydase water not only stimulates neurite generation but also promotes rapid neurite elongation.
The findings from this study clearly demonstrate that while Hydroxydase water has a modest effect on cell proliferation, it remarkably improves the growth and elongation of neurites within a short period of time. This effect is observed across all three concentrations of Hydroxydase water. The increased number and length of neurites highlight Hydroxydase water’s potential as a powerful enhancer of neuronal differentiation and connectivity which should promote neurotransmission in vivo.
Neuronal degeneration is a significant feature observed in mood disorders such as BD and DD. This degeneration is characterized by reductions in neuron density, neurite numbers, and neurite length [5]. Studies have demonstrated poor neurite density in neuron cultures treated with serum from patients with bipolar disorder, particularly in the late stages of the illness [33]. This neuronal loss minimizes synaptic connections and impairs the transmission of electrical signals, leading to weakened neuronal networks that regulate mood and behaviour [2]. Slower and less efficient transmission of neuronal action potentials further exacerbates functional impairments in brain circuits involved in emotional regulation and stress response. These impairments contribute to mood instability, memory deficits, impaired decision-making, and episodes of mania or depression [3,34]. Additional contributors include mitochondrial dysfunction, reduced levels of brain-derived neurotrophic factor (BDNF), and overactivation of glutamate receptors such as N-methyl-D-aspartate (NMDA). The combination of these neurodegenerative factors leads to BD and DD [35,36]. Therefore, only treatments that reverse neurodegeneration and stimulate neuronal growth can effectively minimize the symptoms of BD and DD.
Current treatments for BD and DD primarily address symptoms without focusing on repairing or regenerating neurons [37]. Antidepressants and mood stabilizers, such as selective serotonin reuptake inhibitors (SSRIs)
and anti-inflammatory drugs, provide symptomatic relief but fail to reverse neuronal damage. Neurotrophic therapies like lithium Li aim to enhance BDNF levels, promoting neuronal growth and repair; however, their efficacy remains limited. Furthermore, Li salts cause multiple side effects, including tremors, weight gain, and organ toxicity, necessitating regular blood level monitoring [38]. The use of Mg, either alone or in combination with Li, is also underexplored.
The results of this study demonstrate that exposure of neuronal cells to Li bicarbonate alone is non-cytotoxic at concentrations as high as 100 µg/ml, with no significant effects on neurite generation or length. The median daily doses of Li carbonate or other Li salts range between 600 and 1200 mg/day, administered twice or thrice daily, generating blood concentrations between 0.6 and 1.2 mEq/L (22–44 mg/L). These serum concentrations are too low compared to the doses administered [27]. Although Li is a powerful mood-stabilizing medication, its exact mechanism of action remains unclear, and it has a narrow therapeutic range due to poor intestinal absorption [39]. Thus, finding a safer alternative form of Li, particularly for long-term treatment, is essential.
Hydroxydase, a natural mineral water from the volcanic Auvergne region in France, is rich in ionized lithium (Li+ 9740 µg/L) and magnesium (Mg2+ 243 mg/L). It has been used since 1923 for improving physical and emotional well-being [40] and as a cellular function enhancer [41]. While the exact mode of action underlying its mood-stabilizing properties is unknown, the neuroprotective and neurite growth-promoting effects observed in this study may explain its efficacy. These effects were not seen with Li alone, suggesting that the richness of Hydroxydase in ionized and bioavailable Li and Mg and their synergistic effects on brain neurons are responsible for these properties. Mg levels are known to be low in patients treated with Li-salts [42]. Compared to synthetic Li salts, Li+ in Hydroxydase is likely to better stabilize neurotransmitter levels, promote neuronal growth, and repair structural brain alterations associated with mood disorders. Mg complements Li by acting as an NMDA receptor antagonist, reducing neuronal excitation, modulating neurotransmitter release, and protecting neurons from oxidative damage and inflammation. The exact synergistic mode of action of Li and Mg on neuronal growth still remains unexplored but may have a protective effect on neuronal degeneration through multiple pathways including stimulation of anti-aging gene functions. For instance, it has already been demonstrated that anti-aging gene Sirtuin 1 is critical to neuron proliferation, differentiation and survival, where Mg and Li may play a role of activator, minimizing neuronal degeneration and occurrence of BD/DD [43,44].
The balanced composition of Li and Mg in Hydroxydase is likely to enhance their combined efficacy, providing consistent therapeutic effects without the peaks and troughs associated with tablet-based treatments containing Li salts, such as Li carbonate [45]. Delivered in small, measured doses, Hydroxydase ensures uniform absorption and avoids the cytotoxicity often linked to synthetic drugs. It is bottled directly at the source to preserve its ionized minerals, ensuring long-term stability and effectiveness.
Despite its therapeutic potential, Hydroxydase remains underutilized due to the absence of clinical trials examining the synergistic effects of Li and Mg. As a natural product, it cannot be patented, making it less attractive to pharmaceutical companies. Nevertheless, its unique composition and historical efficacy position it as a valuable alternative for managing BD and DD.
This study was conducted using in vitro neuronal cultures, a controlled environment that excludes neurohumoral influences present in vivo. As such, the observed synergistic effects of Li and Mg on neuronal growth may not fully translate to in vivo conditions. Furthermore, the test substance, Hydroxydase water, contains not only high concentrations of Li and Mg, but also various other minerals and trace elements, which may have contributed to the observed effects. Therefore, caution must be exercised when extrapolating these in vitro findings to potential therapeutic outcome.
Further research is needed to validate and explore the therapeutic benefits of ionized and bioavailable lithium (Li) and magnesium (Mg) as a synergistic, safer, and natural alternative to conventional therapies for treating BD and DD. By addressing the underlying causes of neuronal degeneration, Li+Mg treatments hold promise for more effective management of BD and DD.
The authors thank Ms Léa Shrivastava for her valuable technical and scientific support.
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I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!
"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".
I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.
We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.
I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.
I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.
I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.
Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.
“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.
Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.
Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.
Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.
The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.
Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.
Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.
Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
I would like to offer my testimony in the support. I have received through the peer review process and support the editorial office where they are to support young authors like me, encourage them to publish their work in your esteemed journals, and globalize and share knowledge globally. I really appreciate your journal, peer review, and editorial office.
Dear Agrippa Hilda- Editorial Coordinator of Journal of Neuroscience and Neurological Surgery, "The peer review process was very quick and of high quality, which can also be seen in the articles in the journal. The collaboration with the editorial office was very good."
I would like to express my sincere gratitude for the support and efficiency provided by the editorial office throughout the publication process of my article, “Delayed Vulvar Metastases from Rectal Carcinoma: A Case Report.” I greatly appreciate the assistance and guidance I received from your team, which made the entire process smooth and efficient. The peer review process was thorough and constructive, contributing to the overall quality of the final article. I am very grateful for the high level of professionalism and commitment shown by the editorial staff, and I look forward to maintaining a long-term collaboration with the International Journal of Clinical Case Reports and Reviews.
To Dear Erin Aust, I would like to express my heartfelt appreciation for the opportunity to have my work published in this esteemed journal. The entire publication process was smooth and well-organized, and I am extremely satisfied with the final result. The Editorial Team demonstrated the utmost professionalism, providing prompt and insightful feedback throughout the review process. Their clear communication and constructive suggestions were invaluable in enhancing my manuscript, and their meticulous attention to detail and dedication to quality are truly commendable. Additionally, the support from the Editorial Office was exceptional. From the initial submission to the final publication, I was guided through every step of the process with great care and professionalism. The team's responsiveness and assistance made the entire experience both easy and stress-free. I am also deeply impressed by the quality and reputation of the journal. It is an honor to have my research featured in such a respected publication, and I am confident that it will make a meaningful contribution to the field.
"I am grateful for the opportunity of contributing to [International Journal of Clinical Case Reports and Reviews] and for the rigorous review process that enhances the quality of research published in your esteemed journal. I sincerely appreciate the time and effort of your team who have dedicatedly helped me in improvising changes and modifying my manuscript. The insightful comments and constructive feedback provided have been invaluable in refining and strengthening my work".
I thank the ‘Journal of Clinical Research and Reports’ for accepting this article for publication. This is a rigorously peer reviewed journal which is on all major global scientific data bases. I note the review process was prompt, thorough and professionally critical. It gave us an insight into a number of important scientific/statistical issues. The review prompted us to review the relevant literature again and look at the limitations of the study. The peer reviewers were open, clear in the instructions and the editorial team was very prompt in their communication. This journal certainly publishes quality research articles. I would recommend the journal for any future publications.
Dear Jessica Magne, with gratitude for the joint work. Fast process of receiving and processing the submitted scientific materials in “Clinical Cardiology and Cardiovascular Interventions”. High level of competence of the editors with clear and correct recommendations and ideas for enriching the article.
We found the peer review process quick and positive in its input. The support from the editorial officer has been very agile, always with the intention of improving the article and taking into account our subsequent corrections.
My article, titled 'No Way Out of the Smartphone Epidemic Without Considering the Insights of Brain Research,' has been republished in the International Journal of Clinical Case Reports and Reviews. The review process was seamless and professional, with the editors being both friendly and supportive. I am deeply grateful for their efforts.
To Dear Erin Aust – Editorial Coordinator of Journal of General Medicine and Clinical Practice! I declare that I am absolutely satisfied with your work carried out with great competence in following the manuscript during the various stages from its receipt, during the revision process to the final acceptance for publication. Thank Prof. Elvira Farina
Dear Jessica, and the super professional team of the ‘Clinical Cardiology and Cardiovascular Interventions’ I am sincerely grateful to the coordinated work of the journal team for the no problem with the submission of my manuscript: “Cardiometabolic Disorders in A Pregnant Woman with Severe Preeclampsia on the Background of Morbid Obesity (Case Report).” The review process by 5 experts was fast, and the comments were professional, which made it more specific and academic, and the process of publication and presentation of the article was excellent. I recommend that my colleagues publish articles in this journal, and I am interested in further scientific cooperation. Sincerely and best wishes, Dr. Oleg Golyanovskiy.
Dear Ashley Rosa, Editorial Coordinator of the journal - Psychology and Mental Health Care. " The process of obtaining publication of my article in the Psychology and Mental Health Journal was positive in all areas. The peer review process resulted in a number of valuable comments, the editorial process was collaborative and timely, and the quality of this journal has been quickly noticed, resulting in alternative journals contacting me to publish with them." Warm regards, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. I appreciate the journal (JCCI) editorial office support, the entire team leads were always ready to help, not only on technical front but also on thorough process. Also, I should thank dear reviewers’ attention to detail and creative approach to teach me and bring new insights by their comments. Surely, more discussions and introduction of other hemodynamic devices would provide better prevention and management of shock states. Your efforts and dedication in presenting educational materials in this journal are commendable. Best wishes from, Farahnaz Fallahian.
Dear Maria Emerson, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. I am delighted to have published our manuscript, "Acute Colonic Pseudo-Obstruction (ACPO): A rare but serious complication following caesarean section." I want to thank the editorial team, especially Maria Emerson, for their prompt review of the manuscript, quick responses to queries, and overall support. Yours sincerely Dr. Victor Olagundoye.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews. Many thanks for publishing this manuscript after I lost confidence the editors were most helpful, more than other journals Best wishes from, Susan Anne Smith, PhD. Australian Breastfeeding Association.
Dear Agrippa Hilda, Editorial Coordinator, Journal of Neuroscience and Neurological Surgery. The entire process including article submission, review, revision, and publication was extremely easy. The journal editor was prompt and helpful, and the reviewers contributed to the quality of the paper. Thank you so much! Eric Nussbaum, MD
Dr Hala Al Shaikh This is to acknowledge that the peer review process for the article ’ A Novel Gnrh1 Gene Mutation in Four Omani Male Siblings, Presentation and Management ’ sent to the International Journal of Clinical Case Reports and Reviews was quick and smooth. The editorial office was prompt with easy communication.
Dear Erin Aust, Editorial Coordinator, Journal of General Medicine and Clinical Practice. We are pleased to share our experience with the “Journal of General Medicine and Clinical Practice”, following the successful publication of our article. The peer review process was thorough and constructive, helping to improve the clarity and quality of the manuscript. We are especially thankful to Ms. Erin Aust, the Editorial Coordinator, for her prompt communication and continuous support throughout the process. Her professionalism ensured a smooth and efficient publication experience. The journal upholds high editorial standards, and we highly recommend it to fellow researchers seeking a credible platform for their work. Best wishes By, Dr. Rakhi Mishra.
Dear Jessica Magne, Editorial Coordinator, Clinical Cardiology and Cardiovascular Interventions, Auctores Publishing LLC. The peer review process of the journal of Clinical Cardiology and Cardiovascular Interventions was excellent and fast, as was the support of the editorial office and the quality of the journal. Kind regards Walter F. Riesen Prof. Dr. Dr. h.c. Walter F. Riesen.
Dear Ashley Rosa, Editorial Coordinator, International Journal of Clinical Case Reports and Reviews, Auctores Publishing LLC. Thank you for publishing our article, Exploring Clozapine's Efficacy in Managing Aggression: A Multiple Single-Case Study in Forensic Psychiatry in the international journal of clinical case reports and reviews. We found the peer review process very professional and efficient. The comments were constructive, and the whole process was efficient. On behalf of the co-authors, I would like to thank you for publishing this article. With regards, Dr. Jelle R. Lettinga.
Dear Clarissa Eric, Editorial Coordinator, Journal of Clinical Case Reports and Studies, I would like to express my deep admiration for the exceptional professionalism demonstrated by your journal. I am thoroughly impressed by the speed of the editorial process, the substantive and insightful reviews, and the meticulous preparation of the manuscript for publication. Additionally, I greatly appreciate the courteous and immediate responses from your editorial office to all my inquiries. Best Regards, Dariusz Ziora
