Nutraceuticals for Peripheral Vestibular Pathology: Properties, Usefulness, Future Perspectives and Medico-Legal Aspects
Abstract
:1. Introduction
2. Search Strategy
3. Main Nutraceuticals
3.1. Ginkgo Biloba
Mechanism(s) of Action | Use in Peripheral Vestibular Vertigo/Dizziness | Possible Adverse Events | |
---|---|---|---|
Alpha-lipoic acid | Cofactor in enzymatic processes that produce energy. | Non-specific. | Generally safe, even if skin and gastrointestinal disorders are described [35]. |
Carnosine | Antioxidant, neuromodulatory, antinflammatory, neuroprotective, stimulation of mitochondria [36]. | Non-specific. | NA; probably none [37]. |
Citicoline | Neuroprotective, neuromodulatory, effect on phospholipid synthesis, decrease of their peroxidation, increase of blood flow, cerebral oedema reduction, increase of superoxide-dismutase activity, enhancement of acetylcholine, dopamine and noradrenalin synaptic levels, activation of SIRT-1 and neuronal repair [38,39,40]. | Non-specific, but showed utility in vertigo/dizziness [38,41]. | Safety comparable to placebo. Anxiety, leg oedema (more frequent), depression, falls and incontinence. Reported (not significant): stomach distress, headache, rash, cardiac abnormalities, insomnia, decrease in systolic blood pressure, excitability, restlessness, dizziness. Experimental rats models: creatinine increase, brown urine and lower urine volume in males, mineralisation in both males and females [42,43,44,45]. |
Coenzyme Q10 | Antioxidant, ATP production [46,47]. | MD-like syndromes, preventing hypoxia and improving patients’ symptoms, especially if there is a deficiency [46]. | Generally safe [46]. |
Curcumin | Antioxidant [48]. | Non-specific. | Generally safe [49,50]. |
Ginger | Antithrombotic, antiemetic (blocking 5HT3 receptor), antioxidant, anti-inflammatory (inhibition of COX2, lipoxygenase, and gene encoding inflammatory molecules), anti-infectious, antineoplastic, hypolipidaemic and hypoglycaemic, prokinetic, cardiovascular, thermogenic, analgesic, anti-allergic activity [51,52]. | Non-specific. Effective against nausea and vomiting and with motion sickness. Controversial in vertigo/dizziness [51,53,54]. | Possible adverse events mainly include gastrointestinal symptoms. Sleepiness is also documented, while allergic reactions are rare. There is no solid evidence for interactions with anti-coagulant drugs. Dizziness was described [51,52,55]. |
Ginkgo biloba | Neuroprotective, antioxidative, improvement of cerebral perfusion, stabilization of mitochondria, rheological properties, antinflammatory, antithrombotic and vasorelaxant action, catecholamines modulation. Activity on vestibular system (animal models) [27,28,29]. | Non-specific. Generally useful in vertigo/dizziness [27]. | Increase in blood pressure, dizziness, breathing rate. Poisoning: seizures, legsparalysis, unconsciousness, vomiting (susceptible subjects) [31]. |
Hawthorn | Acts on cardiovascular system and contributes also to relaxation and mental well-being. Hypolipidaemic, hypotensive, cardiotonic, antiarrhythmic, antioxidative activity [56,57]. | Non-specific. | Generally safe. Possible adverse events: gastrointestinal symptoms, dizziness, cardiac complaints [58]. |
Lactium | Calming and sleep-stimulating activity [59]. | Non-specific. | Generally safe. Reported: infections, gastrointestinal symptoms [59]. |
Lemon balm | Action on GABA system, neurocognitive effects and seems to act on cholinergic receptors. Improvements in mood and cognitive performance, antioxidant, anti-inflammatory, anti-nociceptive, hypoglycaemic, hyperlipidaemic, cardiologic, cytotoxic, antimicrobic, antispasmodic, antiepileptic effects are described. May be used in the management of various neurological pathologies or symptoms [60,61,62,63]. | Non specific and generally used in vertigo/dizziness. A formulation containing lemon balm was effective in BPPV [61]. | Generally safe [62]. Rare adverse events (similar to placebo): thyroid hormone inhibition, dizziness, nausea, vomiting, palpitation, wheezing, agitation, increased appetite, EEG changes, reduced alertness, increased intraocular pressure [60]. In mice: prone position, decreased motor activity, difficult breathing, tremors (which resolved spontaneously) [62]. |
Magnesium | Important enzymatic cofactor. Pplays a role in the prevention of various pathologies. Involved in the structural function of nucleic acids, mitochondria, proteins, transport of other ions, DNA/RNA synthesis and aerobic/anaerobic energy production, and many other functions. It can reduce catecholamines [64,65]. | Its deficiency is associated with vertigo [64,66]. Evidence in the treatment of headache/migraine concomitant to vertigo/dizziness, ISHL with vertigo/dizziness, post-stapedectomy vertigo [9,64,67,68,69]. | Hypermagnesemia: vomiting, nausea, headache; absent tendon reflexes, hypotension, somnolence; cardiovascular alteration and hypoventilation; cardio-respiratory arrest, coma, death [64,70]. |
Omega-3 fatty acids | Important role in the production of eicosanoids, such as prostaglandins and leukotrienes. They improve cardiac filling, myocardial efficiency, anti-inflammatory effects, vasodilation. They also regulate ion channel function and provide cellular membrane stability, since they are incorporated in membrane phospholipids [71,72]. | Possible future option in MD [71]. | Generally safe. Possible adverse events: skin eruptions and gastrointestinal symptoms were the most frequent, with the possibility of some laboratory parameter alteration. In dogs and cats: altered platelet and immune function [73,74]. |
Orthosiphon | Antioxidant, anti-inflammatory, analgesic, antihypertensive, renal and hepatoprotective, diuretic, gastroprotective, and many other properties [75]. | Non-specific. | Considered safe. Liver hypertrophy is a possible adverse event [75]. |
Polygonum | Immunomodulating, antioxidant, anti-cancer, neuroprotective, anti-ageing, hepatoprotective, anti-hyperlipidaemia, anti-inflammatory [76]. | Non-specific. | Generally safe. Certain components or preparations may generate nephrotoxicity, hepatotoxicity, lung damage [76]. |
Sage | Anti-inflammatory, antidepressant, anxiolytic, antioxidative, antimicrobial, anticancer, antinociceptive, antidementia, hypoglycaemic, hypolipidaemic properties. It inhibits AChE (cholinergic activity) and inhibits the GABAA receptor (through thujone) [77,78,79,80]. | Non-specific. Effective in vertigo/dizziness [79]. | Generally safe. Reported signs and symptoms include: salivation, gastrointestinal symptoms, tachycardia, skin eruption, hot flushes, hypersensitivity, cyanosis, increased blood pressure, and convulsion [77,79,80]. |
SPC-flakes * | Contain AF. It may regulate ions and water, interacting with aquaporins and modulating chloride homeostasis [81]. | Used in MD [81,82]. | No adverse events reported [81,83]. |
Vinitrox | Combination of apple and grape polyphenols with vasodilator and antioxidant effect [61]. | Non-specific. | NA. |
Vitamin B | Vitamin B6 protects circulation and seems to facilitate vestibular system, acting on vertigo [61,84,85]. Vitamin B2, B3, and B6 aid nervous system. B2 and B3 also maintain mucous membranes [56]. | Vitamin B deficiency, in general, may lead to neurological symptoms, also dizziness and vertigo [86,87]. | Possible toxicity (rare). Vitamin B12: transientchromaturia, skin eruptions, CNS manifestations, increased bloodpressure, gastrointestinal symptoms [88]. Vitamin B3: flushing, skin and gastrointestinal manifestations, headache, light-headedness [89]. Vitamin B6: neurological symptoms [90]. |
Vitamin C | It is a radical scavenger that gave an improvement in MD control, considering an oxidative insult as a basis for MD origin: controversial in a study. Vitamin C also contributes to nervous system function [91,92,93]. | Non-specific. Maybe useful in MD [92]. | Rare adverse events: gastrointestinal symptoms, kidney stones in men [94]. |
Vitamin D | Vitamin D deficiency/alterations of calcium metabolism are also risk factors for recurrence, and probably pathogenic factors of BPVV, immunomodulatory activity (immune system role on MD) [95,96,97,98]. | Vitamin D supplementation in BPVV showed a 24% lower recurrence for patients with low serum levels. Class III evidence. Possible role in MD [95,96,97,98]. | Gastrointestinal symptoms. Intoxication: hypercalcemia, hypercalciuria. This potentially leads to muscle weakness, hypertension, neuropsychiatricdisturbances, gastrointestinal upset, polyuria and polydipsia, renal calculi, and, in extreme cases, renal failure, arrhythmias [95,99]. |
Vitamin E | Antioxidant [47,100]. | Non-specific. | Intoxication: increase of bleeding risk, hepatobiliary disfunction, malabsorption of other fat-soluble vitamins [101]. |
Zinc and copper | Antioxidant [56]. | Non-specific. | Zinc (intoxication): Gastrointestinal symptoms, muscle cramps, rare cases of kidney injury [102]. Copper (intoxication): neurological, liver damage (similar to Wilson’s disease) [103,104]. |
Metabolism by CYP or Transporters | Action on CYP or Transporters | Theorical or Factual Pharmacodynamic Interactions | |
---|---|---|---|
Citicoline | NA. | NA. | Increases vertigo/dizziness feeling: interacting with antibiotics (aminoglycosides, macrolides, glycopeptides), antimalarial drugs, NSAIDs, and acetylsalicylic acid, which also cause vertigo/dizziness [45,105]. Increased activity of antihypertensive drugs [42]. Increased levels of acetylcholine [38,39]. Increased levels of dopamine, noradrenaline and serotonin; this generates interference with drugs acting on these pathways [38,39]. |
Ginger | NA. | In vitro inhibition of CYP2C9, 2C19 2D6, and CYP 3A4 [51,106]. Inhibition of P-gp in vitro [51,106]. | Anti-allergic activity: increased effects of antihistamines. Increased risk of bleeding [51,52]. Hypoglycemic effects [51]. It blocks 5HT3 receptor similarly to ondansetron; increased activity [51]. Anti-allergic activity: increased effects of antihistamines with increased risk of sleepiness [51,52]. |
Ginkgo biloba | NA. | Inhibition of CYP1A2, CYP2C9, CYP2E1, CYP3A4, and P-gp [32]. | Increased effects of cilostazol or anticoagulants with increase in bleeding time [31,34]. Increase in vertigo/dizziness feeling: interaction with antibiotics (aminoglycosides, macrolides, glycopeptides), antimalarial drugs, NSAIDs, and acetylsalicylic acid, which causes vertigo/dizziness [31,105]. Proconvulsant effect: interaction with anti-epileptic drugs [107]. Increase of acetylcholine levels [108]. Increase of dopamine and noradrenaline levels [108]. |
Hawthorn | No strong information. Some authors described a new CYP450 enzyme responsible for terpenoids C-2α hydroxylation [109]. | NA. | Increased activity of beta-blockers, digitalis, and hypotensive drugs [57]. Increased activity of antihypertensive drugs [57]. |
Lemon balm (Melissa officinalis) | NA. | NA. | Action on GABA receptors: may increase the effects of BDZ [61,63]; Hypoglycemic effects [60]. Increase of vertigo/dizziness feeling: interaction with antibiotics (aminoglycosides, macrolides, glycopeptides), antimalarial drugs, NSAIDs, and acetylsalicylic acid, which causes vertigo/dizziness [60,105]. Increase in intraocular pressure: pay attention to patients with glaucoma [60]. Action on acetylcholine pathways: may interact with cholinergic and anticholinergic drugs [63]. Associated with tremors: pay attention to patients with Parkinson’s disease [62]. |
Magnesium | NA. | NA. | Increased activity of antihypertensive drugs. Loop diuretics may cause hypomagnesemia [110]. |
Omega-3 fatty acids | Omega-3 and omega-6 can be metabolized by CYP1A1, CYP2E1, CYP2C, CYP2J2, CYP4A, CYP4F, and other isoforms as efficient alternative substrates of arachidonic acid metabolizing CYP enzymes [111]. | NA. | NA. |
Ortosiphon | NA. | In vitro inhibition of CYP2C19, CYP2D6, and CYP3A4 [112,113]. | Anti-seizure activity: may increase anti-epileptics activity [114]. Increased activity of antihypertensive drugs [75]. |
Polygonum | NA. | Induction of CYP2C9 and CYP3A4 [115]. Inhibition of CYP3A and MRP [116]. | May be useful in Parkinson’s disease [76]. |
Sage (Salvia officinalis) | NA. | Components act on CYP450: among phenolic acids, TSIIA inhibited CYP2C9/3A4, whereas SAB induces it [117]; among the terpenoids, salvinorin A showed to be a CYP1A1 2C18, 2D6, and 2E1 substrate [117]. Inhibition of CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 [117]; Induction of CYP1A2 and CYP3A4 [117]. Some compounds showed activity on P-gp and OAT [117]. | Inhibition of GABAA receptors: decreased effects of BDZ [77,80]; Inhibition of AChE: this may lead to an interaction with cholinergic or anticholinergic drugs [77]. Increase risk of bleeding [117]. Hypoglycemic effects [79,117]. Increase of vertigo/dizziness feeling: interaction with antibiotics (aminoglycosides, macrolides, glycopeptides), antimalarial drugs, NSAIDs, and acetylsalicylic acid, which causes vertigo/dizziness [105,117]. Proconvulsant effects: interaction with anti-epileptic drugs [79,80]. It may reduce tremors: enforces the action of drugs used in neurological diseases [79]. Associated with both increased and decreased blood pressure [77,80]. |
3.2. Ginger
3.3. Citicoline
3.4. Magnesium
3.5. Lemon Balm
3.6. Sage
3.7. Omega-3 Fatty Acids
3.8. Specially Processed Cereals (SPC) Flakes
3.9. Other Compounds/Supplements
4. Discussion
5. Medico-Legal Aspects
Author Contributions
Funding
Conflicts of Interest
References
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Clinical Manifestation | Pathogenesis | Symptoms | Treatment | References |
---|---|---|---|---|
Benign paroxysmal positional vertigo | Mainly idiopathic, but vestibular neuritis, head trauma, and MD may be related to it. Risk factors include advanced age, ear and dental surgery, vitamin D deficiency, perimenopause, and maybe vascular disorders. Dislocation of the otoconia has a crucial role. | Vertigo, nausea, light headiness. | Vestibular maneuvers, vestibular suppressants. | [7,9,10,11,12,13,14,15,16] |
Vestibular neuritis | Uncertain aetiology (e.g., vascular, viral, immunologic, or inflammatory). | Nystagmus, posture alteration, or gait abnormalities. | Vestibular suppressants, steroids, rehabilitation. | [7,9,10] |
Ménière’s disease | Endolymphatic hydrops generated by genetic, autoimmune/allergic, vascular, infectious, and mechanic conditions. | Hearing loss (sensorineural, in the low and middle frequencies), vertigo attacks, tinnitus, aural fullness. | Dietary/lifestyle approach, diuretics, betahistine, antiemetic benzodiazepines, anticholinergics, antihistamines, phenothiazines, ondansetron, surgery. | [7,9,10] |
Bilateral vestibulopathy | The aetiology often remains unclear. Frequent known causes are ototoxic drugs, bilateral MD, meningitis, and genetic mutations. | Postural imbalance and unsteadiness of gait (both worsen in darkness and on uneven ground); oscillopsia (induced by head or body movement). | It may change on the basis of the aetiology. Rehabilitation, vestibular implants, vestibular stimulation. | [17,18] |
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Chiarella, G.; Marcianò, G.; Viola, P.; Palleria, C.; Pisani, D.; Rania, V.; Casarella, A.; Astorina, A.; Scarpa, A.; Esposito, M.; et al. Nutraceuticals for Peripheral Vestibular Pathology: Properties, Usefulness, Future Perspectives and Medico-Legal Aspects. Nutrients 2021, 13, 3646. https://doi.org/10.3390/nu13103646
Chiarella G, Marcianò G, Viola P, Palleria C, Pisani D, Rania V, Casarella A, Astorina A, Scarpa A, Esposito M, et al. Nutraceuticals for Peripheral Vestibular Pathology: Properties, Usefulness, Future Perspectives and Medico-Legal Aspects. Nutrients. 2021; 13(10):3646. https://doi.org/10.3390/nu13103646
Chicago/Turabian StyleChiarella, Giuseppe, Gianmarco Marcianò, Pasquale Viola, Caterina Palleria, Davide Pisani, Vincenzo Rania, Alessandro Casarella, Alessia Astorina, Alfonso Scarpa, Massimiliano Esposito, and et al. 2021. "Nutraceuticals for Peripheral Vestibular Pathology: Properties, Usefulness, Future Perspectives and Medico-Legal Aspects" Nutrients 13, no. 10: 3646. https://doi.org/10.3390/nu13103646