The Beneficial Effects of Pomegranate on Hearing of Patients Without Hemodialysis
Condition: Hearing Impairment
MeSH terms: Hearing Loss; Deafness
Study type: Interventional

Summary: 
      Pomegranate has anti-oxidative capacity. It might reduce symptoms of Alzheimer's disease,
      Drug-induced hepatitis, and might prevent deterioration of cardiovascular diseases and cancer
      progression. But, the beneficial effects of pomegranate on hearing impairment was still
      unclear.

      This study aimed to investigate the beneficial effects of pomegranate on hearing impairment
      by a prospective, randomized, double-blinded clinical trial design. The investigators'll
      include 120 elderly patients without hemodialysis in our hospital, and divided them into 2
      groups. Control group will receive placebo treatment; pomegranate group will receive oral
      pomegranate (500 mg, twice per day).

      All patients received the above treatment for 9 months, and underwent pure tone audiometry
      and word discrimination scores before the start of the clinical trial and at the end of the
      treatment (9th month).
    

Detailed description: 
      Pomegranate has anti-oxidative capacity. It might reduce symptoms of Alzheimer's disease,
      Drug-induced hepatitis, and might prevent deterioration of cardiovascular diseases and cancer
      progression. But, the beneficial effects of pomegranate on hearing impairment was still
      unclear.

      This study aimed to investigate the beneficial effects of pomegranate on hearing impairment
      by a prospective, randomized, double-blinded clinical trial design. The investigators'll
      include 120 elderly patients without hemodialysis in our hospital, and divided them into 2
      groups. Control group will receive placebo treatment; pomegranate group will receive oral
      pomegranate (500 mg, twice per day).

      All patients received the above treatment for 9 months, and underwent pure tone audiometry
      and word discrimination scores before the start of the clinical trial and at the end of the
      treatment (9th month).

      <background> Age-related hearing impairment (ARHI) was very common in the elderly. Hearing
      deteriorated not only due to problems with the peripheral hearing organs, but also because of
      degeneration of the central auditory system. In general, peripheral hearing deteriorates more
      quickly and severely in male subjects than in female subjects, more severely at higher than
      low frequencies, and more quickly in the central auditory system than the peripheral hearing
      organs.

      1.

      Mechanisms of ARHI:

      In addition to genetic susceptibility, environmental factors, including obesity, obstructive
      sleep apnea, systemic diseases, noise, chemical exposure, alcohol, tobacco, ototoxic
      medication, diet, hormonal factors, menopause and socioeconomic status, may also contribute
      to hearing degeneration. Contributing mechanisms of this disease may include
      hypoxia/ischemia, reactive species formation, oxidative stress, and apoptotic/necrotic death
      of inner ear hair cells/spiral ganglion cells, neural cells, or vascular endothelial cells.

      Poor serum vitamin B-12 and folate status levels may be associated with age-related auditory
      dysfunction in older females. Elevated plasma methylmalonic acid (MMA) concentration may be
      associated with hearing loss in older adults. Hearing function of noise-exposed workers was
      negatively correlated with plasma vitamin E levels.

      But, one report reported that plasma levels of homocysteine, erythrocyte folate and vitamin
      B6 were not associated with severity of age-related hearing impairment. Serum magnesium and
      vitamin C levels were also not correlated with severity of noise-induced hearing loss. The
      glutathione peroxidase (GPx) 6 gene was upregulated while the thioredoxin reductase 1 gene
      was downregulated in mice with ARHI. Furthermore, our study group had found that plasma
      reactive oxygen species levels were correlated with severity of ARHI in humans.

      2.

      Prevention and/or treatment of ARHI It is reasonable to expect that improved endogenous
      antioxidant capacity and/or exogenous antioxidant supplementation may suppress oxidative
      damage to the cells of auditory system.

      Some agents were reported to be beneficial for the senescent auditory system. For example,
      (-)-Epigallocatechin-3-gallate(EGCG) could protect cultured spiral ganglion cells from
      hydrogen peroxide-induced oxidizing damage. Vitamin C or E could prevent ARHI in animals.
      Coffee and caffeine were good for auditory neuropathy of mice. Also, antioxidants were also
      beneficial for the senescent auditory cortex of aged rats. B12 supplementation could prevent
      hearing loss in B12-deficient individuals. Folic acid supplementation slowed hearing decline
      slightly in low frequencies, but not in high frequencies in a population without folic acid
      fortification of food. Higher folate intake had lower risk of developing hearing loss in
      older males. Coenzyme Q10 (CoQ10) could slow down the deterioration of presbycusis. There was
      an inverse association between higher intakes of long-chain n23 poly-unsaturated fatty acid
      (PUFAs) and regular weekly consumption of fish and age-related hearing loss. Patients who
      achieved the highest plasma concentrations of vitamin C, vitamin E and selenium had
      significantly less loss of high-tone hearing. And, salicylate use and moderate alcohol intake
      were possible protective factors for ARHI.

      But, report claimed that life style with higher intake of vitamin C, E, beta carotene, or B12
      did not reduce the risk of hearing loss in adult males. Vitamin E or atorvastatin cannot slow
      down the deterioration of presbycusis. Low-dose difluoromethylornithine (DFMO) could not
      protect hearing.

      3.

      Introduction of pomegranate:

      Pomegranate is a subtropical and tropical fruit of great importance from a health point of
      view. It has antioxidant activity and antimutagenic potential. Oxidative and histologic
      evaluation showed that pomegranate juice might have a preventive effect in
      paracetamol-induced acute liver damage. Six weeks supplementation of pomegranate juice could
      have favorable effects on oxidative stress in patients with type 2 diabetes. Pomegranate
      extract alleviates disease activity and some blood biomarkers of inflammation and oxidative
      stress in rheumatoid arthritis patients.

      Pomegranate seed extract exhibited therapeutic potential for memory and muscular coordination
      in rats, which was most likely related at least in some part to its antioxidative and free
      radical scavenging actions. Long-term dietary supplementation with pomegranates from Oman
      attenuates cognitive and behavioral deficits in a transgenic mice model of Alzheimer's
      disease. Consumption of pomegranates improves synaptic function in a transgenic mice model of
      Alzheimer's disease. Pomegranate's neuroprotective effects against Alzheimer's disease are
      mediated by urolithin, its ellagitannin-gut microbial derived metabolites.

      A systematic review and meta-analysis of randomized controlled trials (RCTs) did not suggest
      any effect of pomegranate consumption on lipid profile and on plasma c-reactive protein
      levels. One report also concluded that the quality of previous studies about the use of
      dietary pomegranate preparations in the prevention and treatment of cardiovascular diseases
      was poor. Even in the best studies, indications of benefit did not reach the conventional
      levels of statistical significance. And, future studies need to prove the clinical benefit.

      Methanol extract of pericarp of pomegranate (PME) had anti-proliferative effect on human
      breast (MCF-7, MDA-MB-231), endometrial (HEC-1A), cervical (SiHa, HeLa), and ovarian (SKOV3)
      cancer cell lines, and normal breast fibroblasts (MCF-10A). Also, PME could modulate
      osteoblastic cell differentiation. Pomegranate evokes antiproliferative, anti-invasive, and
      antimetastatic effects, induces apoptosis through the modulation of Bcl-2 proteins,
      upregulates p21 and p27, and downregulates cyclin-cdk network. Furthermore, pomegranate
      blocks the activation of inflammatory pathways including, but not limited to, the nuclear
      factor kappa-light-chain-enhancer of activated B cells(NF-κB) pathway. However, another
      meta-analysis showed that the evidence of clinical effectiveness for cancer treatment in
      humans was poor because the quality of the studies was poor.

      4.

      Pomegranate:

      A new candidate for ARHI treatment? Pomegranate has antioxidative capacity and could prevent
      Alzheimer's disease. Meanwhile, oxidative damage was one of the underlying mechanisms for
      ARHI. So, it is reasonable to expect that pomegranate might have a beneficial effect for
      ARHI.
    

Intervention name(s): Placebo; Pomegranate
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): The gel contains a mixture of glucose and maltodextrin - a complex carbohydrate - along with fat and a trace of protein.; Pomegranate extract 500mg
Other intervention name(s): Maltodextrin; Pomegranate extract
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Supportive Care
Keywords: Pomegranate; Hearing