xRead - Olfactory Disorders (September 2023)

20426984, 2022, 4, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/alr.22929, Wiley Online Library on [04/09/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License

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PATEL et al.

olfactory loss increased recovery rates in patients treated with zinc gluconate when compared with controls. 451 At oral doses traditionally used for chemosensory dys function, zinc can have side effects such as iron deficiency anemia, copper deficiency, gastric distress, neutropenia, and impaired immune function. 451 Intranasal zinc administration is marketed as a treat ment for the common cold, and there are multiple low-quality, small studies highlighting zinc-induced per manent anosmia. Eby et al 1568 proposed that it would be unethical to introduce zinc to the interior of the nose. Use of zinc to treat OD Aggregate grade of evidence : B (Level 1: one study; Level 2: two studies; Level 3: three studies). Benefit : In patients with OD, the response rate of symp toms to oral zinc supplements is similar to spontaneous recovery, with no statistically significant improvement, except in one study assessing posttraumatic dysfunction. Intranasal zinc treatment shows no benefit and likely harm. Harm : Iron deficiency anemia, copper deficiency, gas tric distress, neutropenia, and impaired immune func tion in select patients. Possible irreversible anosmia with intranasal application. Cost :Minimal. Benefits-harm assessment : There is no advantage of using either oral or intranasal zinc treatment in patients with OD, with no consolidated evidence of statistically sig nificant improvements, and potential minor harm caused by oral zinc and significant potential harm caused by intranasal zinc. Value judgments : There does not appear to be any value added by using zinc in the treatment of most forms ofOD. Policy level : Oral zinc treatment for PTOD: option. Oral zinc treatment for non-PTOD: recommendation against. Intranasal zinc treatment: recommendation against. Intervention : Zinc treatment should not currently be used to treat most patients with OD. c. α-Lipoic acid Typically used as a nutritional supplement and antioxidant for diabetic neuropathy, α -lipoic acid was considered a can didate for olfactory recovery with increased expression of nerve growth factor, substance P, and neuropeptide Y. It also has neuroprotective capabilities that may prevent neu ral damage involving free radicals. Only one study has examined the use of α -lipoic acid in olfactory loss. Hummel et al 1569 conducted a prospective, unblinded, noncontrolled trial using α -lipoic acid treat ment (600 mg daily) in 23 patients with PVOD. After a median of 4 months of treatment, 61% of patients demon

strated some improvement in TDI scores, with 35% improv ingby > 5.5. A weak correlation was seen between age < 60 years and improved recovery. With no control group, and no time from loss restriction, spontaneous improvement cannot be ruled out. No patients in the study reported severe adverse reactions. The use of α -lipoic acid is normally well tolerated, with a small risk of nausea, rash, and liver enzyme elevation at high doses. Patients with DM have a small risk of medication interaction and hypo glycemia. No other study has been completed to support this finding. Useof α -lipoic acid to treat OD Aggregate grade of evidence : D (Level 4: one study). Benefit : Potential improvement in OF (primarily threshold). Harm : Low risk of hypoglycemia, nausea. Cost : Minimal $1 USD per day for a 600-mg dose. Benefits-harm assessment : Not enough data to inter pret potential benefit, but relatively low harm. Value judgments : Not enough evidence exists to sup port value in use for OD. Policy level : No recommendation for use of α -lipoic acid to treat OD. Intervention : More data are needed before clinicians can present this as a beneficial treatment option for their patients. d. Vitamin A In humans, only five studies have focused on the role of vitamin A in olfaction. The first of these studies, a case series reported by Duncan and Briggs, 1570 reported bene ficial effect with high-dose systemic vitamin A therapy in 50 of 56 patients. Another study showed that oral substi tution of vitamin A at 10,000 μ g/day for 4 weeks cured olfactory loss in patients with liver cirrhosis and vita min A deficiency. 1510 More recently, however, a double blind placebo-controlled trial by Reden and colleagues 456 using a more moderate oral dose of 10,000 IU/day for 3 months, reported no significant improvement in olfac tory test scores following treatment with oral vitamin A. 456 Kartal et al 1571 observed a significant improvement in odor identification after a noncontrolled 3-month sys temic treatment with isotretinoin (synthetic analogue of vitamin A) in patients with acne. More convincing evi dence comes from a retrospective controlled study with local vitamin A application. 1572 The combined therapy of OT with intranasal vitamin A in a dose of 10,000 IU/day for 2 months produced significantly greater improvement compared with pure OT in patients with postinfectious smell loss. Further, an RCT with a similar experimen tal approach (vitamin A at 10,000 IU/day with OT ver sus vitamin A versus standard therapy) is currently being performed in Canada with a large number of patients