News & Notes: Antioxidants for Relief from Tinnitus; Lutein and Zeanthin for Healthy Eyes; Fish Oils for Seniors

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Alpha Lipoic Acid

Tinnitus and Oxidative Stress

by Jule Klotter

Oxidative stress is a major factor underlying the ringing, roaring, or other annoying (even debilitating) sounds that characterize tinnitus. Those sounds can cause sleep disorders, depression, and impair social cohesion and quality of life.

Cochlear degeneration is the main cause of tinnitus. Oxidative stress is known to produce cochlear degeneration and changes in auditory hair cells and nerve fibers. As Celik and Koyuncu explain in their 2018 article, “The sensorineural epithelial tissues of the cochlea are more susceptible to deleterious effects caused by free radicals than other tissues of the body.”

Because of the known relationship between oxidative stress and tinnitus, and because tinnitus patients have “higher plasma concentrations of oxidative stress biomarkers and lower antioxidant activity” than healthy people, a group of Greek researchers, led by Anna I. Petridou, decided to test the effects of supplementation on people with tinnitus. Their 2019 randomized, double-blind, placebo-controlled trial enrolled 70 people, between 25 and 75 years old.

All participants had tinnitus in one or both ears for at least six months; the noise required at least 5 decibels of competing sound to mask it. Inclusion criteria also included a score of 4 or above on the Tinnitus Handicap Inventory (THI) questionnaire, which assesses the emotional and functional impacts of having tinnitus. Participants needed to have normal hearing or only moderate hearing loss.

Exclusion criteria included Meniere’s disease, otosclerosis, several chronic conditions and use of tinnitus-inducing medication (e.g., aminoglycosides, chemo-therapeutics, loop diuretics, high doses of aspirin or quinine). Three participants (2 placebo group; 1 antioxidant group) discontinued the trial, due to unscheduled surgery; and four in the placebo group were lost to follow-up.

Participants underwent a baseline assessment that included anthropometric, audiometric, and tinnitus psychoacoustic measures; tinnitus discomfort; psychological symptoms; physical activity; and dietary assessment as well as blood sample collection. Participants were re-assessed three months later, at study’s end.

The treatment group took a commercially available multivitamin-multimineral supplement (Lamberts), which included 500 mg of standardized grape seed extract once a day with a meal. Grape seed extract is a rich source of phenolic compounds, such as epicatechin, resveratrol and procyanidin oligomers; “many experimental studies have proven the protective effect of polyphenols against cisplatin-induced ototoxicity and cochlear hair cell damage after intense noise exposure.”

Participants in the treatment group also took one tablet of alpha-lipoic acid (300 mg) twice a day on an empty stomach. Animal and human studies show that alpha-lipoic acid protects against noise-induced hearing loss. The placebo group took three placebo pills with similar shape and colour to the supplements, made by a local manufacturing pharmacy. An investigator, uninvolved in the study, packaged the supplements and the placebos in identical containers and bags and labeled each with a participant’s number.

At study’s end, only participants in the supplement group had a significant reduction in tinnitus loudness from baseline, reflected in lower minimum masking levels (p<0.001). The supplement group also had a mean reduction in the Tinnitus Handicap Inventory of 6 points (“considered clinically relevant”). Also, the supplement group, unlike the placebo group, displayed “a significant decrease in the auditory threshold at the frequencies of 250 Hz, 500 Hz, 1000 Hz, 2000 Hz and 6000 Hz” – that is, their hearing improved.

Blood serum changes in total antioxidant capacity, superoxide dismutase, and oxidized LDL were insignificant.

The authors note that the commercial multivitamin and mineral supplement used in this study contained only 150 mg of vitamin C and only 100 mg (150 iu) of vitamin E (dl-alpha tocopherol acetate), but they did not want to use isolated nutrients: “…our hypothesis was that an antioxidant combination might be more effective compared with single nutrients, since various antioxidants have a synergistic/complementary activity.” Although the combination of vitamins, minerals, phytochemicals, and alpha lipoic acid reduced tinnitus intensity and patient discomfort, they would like to see further investigation on its possible effect on oxidative stress biomarkers.

Celik M, Koyuncu I. A Comprehensive Study of Oxidative Stress in Tinnitus Patients. Indian J Otolaryngol
Head Neck Surg. Oct-Dec 2018;70(4):521-526.
Petridou Ai, et al. The Effect of Antioxidant Supplementation in Patients with Tinnitus and Normal
Hearing or Hearing Loss: A Randomized, Double-Blind, Placebo Controlled Trial. Nutrients.
December 12, 2019.
Reprinted with permission from Townsend Letter (April 2021):

Lutein and Zeaxanthin Are Still the Nutrients of Choice for Healthy Eyes

(The Council for Responsible Nutrition)

Sure, you should still eat your carrots – they’re good for your eyes. And you should also be aware of studies like this one that show lutein, zeaxanthin and meso-zeaxanthin are found in the human macula. As a result, these carotenoid antioxidant supplements may protect the retina and actually act to filter blue light (which we’re all getting so much of).
This review of 46 studies found that macular pigment optical density increased among adults with healthy eyes – particularly at higher doses of lutein/zeaxanthin intake. More research is called for in order to find the most effective minimal doses and how long the supplements should be taken.
(The Effect of Lutein / Zeaxanthin Intake on Human Macular Pigment Optical Density: A Systematic Review and Meta-Analysis. Wilson LM, Tharmarajah S, Jia Y, Semba RD, et al. Adv Nutr. 2021 Jun 22:nmab071. doi: 10.1093/advances/nmab071.

Different types of fish oil supplements may work in distinct ways

(The Council for Responsible Nutrition)

A small randomized double-blind trial led by researchers at Tufts University suggests that the omega-3 fatty acids EPA and DHA have different effects on chronic inflammation in older obese adults. The study participants were randomly assigned to receive either EPA or DHA fish oil supplements twice a day. Research shows that these fatty acids can lower risk of heart disease, probably by reducing inflammation. These results suggest that DHA is the more powerful of the two on markers of inflammation in the body, although the researchers found that EPA was better than DHA at enhancing crucial balance between the two. “For the prevention of cardiovascular disease, previous research tells us that balance is very important,” explained first author Jisun So.
EPA and DHA differentially modulate monocyte inflammatory response in subjects with chronic inflammation in part via plasma specialized pro-resolving lipid mediators: A randomized, double-blind, crossover study. Atherosclerosis. So, J., Wu, D., Lichtenstein, A.H., Tai, A.K., et al. (2020).
Background and aims: The independent effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on chronic inflammation through their downstream lipid mediators, including the specialized pro-resolving lipid mediators (SPM), remain unstudied. Therefore, we compared the effects of EPA and DHA supplementation on monocyte inflammatory response and plasma polyunsaturated fatty acids (PUFA) SPM lipidome.
Methods: After a 4-week lead-in phase (baseline), 9 men and 12 postmenopausal women (50-75 years) with chronic inflammation received two phases of 10-week supplementation with 3 g/day EPA and DHA in a random order, separated by a 10-week washout.
Results: Compared with baseline, EPA and DHA supplementation differently modulated LPS-stimulated monocyte cytokine expression. EPA lowered TNFA (p < 0.001) whereas DHA reduced TNFA (p < 0.001), IL6 (p < 0.02), MCP1 (p < 0.03), and IL10 (p < 0.01). DHA lowered IL10 expression relative to EPA (p = 0.03). Relative to baseline, EPA, but not DHA, decreased the ratios of TNFA/IL10 and MCP1/IL10 (both p < 0.01). EPA and DHA also significantly changed plasma PUFA SPM lipidome by replacing n-6 AA derivatives with their respective derivatives including 18-hydroxy-EPA (+5 fold by EPA) and 17- and 14-hydroxy-DHA (+3 folds by DHA). However, DHA showed a wider effect than EPA by also significantly increasing EPA derivatives and DPA-derived SPM at a greater expense of AA derivatives. Different groups of PUFA derivatives mediated the differential effects of EPA and DHA on monocyte cytokine expression.
Conclusions: EPA and DHA had distinct effects on monocyte inflammatory response with a broader effect of DHA in attenuating pro-inflammatory cytokines. These differential effects were potentially mediated by different groups of PUFA derivatives, suggesting immunomodulatory activities of SPM and their intermediates.

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