The Beneficial Effects of Pomegranate on Hearing of Patients Without Hemodialysis
The Beneficial Effects of Pomegranate on Hearing of Patients Without Hemodialysis
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 will receive above treatment for 9 months, and receive examinations of pure tone
 audiometry, word discrimination score before start of this clinical trial, 4.5th month after
 the start day, the end of treatment (the 9th month), and 4.5 months after the treatment (the
 13.5th month).
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 will receive above treatment for 9 months, and receive examinations of pure tone
 audiometry, word discrimination score before start of this clinical trial, 4.5th month after
 the start day, the end of treatment (the 9th month), and 4.5 months after the treatment (the
 13.5th 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.
Inclusion Criteria:

 1. Age 50 to 80 years old.

 2. non-renal dialysis patients.

 Exclusion Criteria:

 1. Life can not take care of themselves or the bed of a patient.

 2. dialysis patients.

 3. Patients who can not understand the details of this study or are unable to cooperate
 with the examination.

 4. history of alcohol or drug abuse.

 5. history of high environmental noise exposure.

 6. The pure tone hearing threshold is greater than 10 decibel (dB), and the audiogram 4
 kilohertz (kHz) air conduction threshold is greater than 8 kilohertz (kHz) air
 threshold value of 20 decibel (dB).