Ringing in your ears? Genetics, Tinnitus, and Meniere’s disease

Vertigo, constant ringing, and nausea…  It sounds like a trip on a roller coaster after drinking a cherry slushie!  This describes everyday life for many people with Meniere’s disease, an inner ear disorder causing vertigo and ringing in the ear. Meniere’s can also cause pressure in the ear and possible hearing loss, most often striking people in their 40s and 50s.

Most health websites claim Meniere’s is a chronic condition: no cure and without an exact cause. (article)(article)

So let’s dig into the incurable disease with no real cause… looking at the most up-to-date research and examining the genetic links. Additionally, we will look at tinnitus on its own – and as a part of Meniere’s. I’ll round out this article with the research on solutions for Meniere’s disease and for tinnitus.

Meniere’s, tinnitus, and how the ear works:

Let’s start off with some background information on how the ear works – and how this ties into balance.

Your balance is coordinated by the change in motion of the fluid in the inner ear.  It is like a built-in accelerometer that knows when you are in motion. Peripheral vertigo, or feeling dizzy and off-balance, is due to inner ear dysfunction. The sense of balance gets messed up by signals being sent to the brain that doesn’t match up with reality.

Within the inner ear, a spiral-shaped cavity called the cochlea is dedicated to hearing. Also, the inner ear contains the vestibular system responsible for your balance. [ref] So you can imagine that something disturbing and pressing on the vestibular system could cause vertigo as well as impacting hearing.

Endolymph is the fluid inside the inner ear. This fluid is moving and transmitting sounds, movement, etc to the brain. The makeup of the ions in that fluid is really important for transmitting signals to the brain. Within the cochlea, the endolymph has very low calcium (Ca2+) concentration, which allows better mechanoelectrical transduction with the little hair cells in the cochlea. [ref]

Here is a picture of the structure of the ear so you can visualize where the inner ear is – with the vestibular area and the cochlea. (Creative Commons License- Wikimedia commons.):

File:1404 The Structures of the Ear.jpg

 

What is going wrong in Meniere’s disease?

Researchers think that too much potassium (K+) in the inner ear causes too much endolymph in the vestibular organ. Any excess fluid is normally stored in an endolymphatic sac. In Meniere’s, the storage sac is thought to fill up with too much fluid, ballooning, and pressing on the hearing parts of the ear, causing hearing loss.  A rupture of the membrane in this area can cause severe vertigo.

Often the symptoms in Meniere’s fluctuate, with the vertigo attacks suddenly becoming severe to the point of causing nausea and vomiting. The attacks sometimes may be preceded with changes in tinnitus, hearing, and the ear feeling full. [ref]

The membrane can heal up pretty quickly, leading to a cycle of increasing fluid and eventual rupture. Tinnitus and vertigo can fluctuate during the cycle when the fluid is building back up again.

Digging a little deeper:
So what do potassium and other ions have to do with fluid in the ear?  Think back to osmosis experiments in high school science class… fluid can be drawn across a membrane to balance out ions.

The endolymph fluid has a different ion concentration and pH from the rest of the ear.  The sodium concentration is higher and the potassium and chloride concentrations are lower. Researchers think the ion gradient gets messed up (too much potassium) which is then balanced out with more fluid, causing swelling.

The cells surrounding the endolymphatic sac have receptors activated by cortisol and also receptors sensitive to aldosterone. Aldosterone is the hormone that controls the absorption of salt in the kidneys and is important in blood pressure. [ref] This ties Meniere’s to both blood pressure and to stress (cortisol).

This general explanation of Meniere’s disease may not be the whole story.  Researchers note that some people have swelling within the endolymph system and don’t have the symptoms of Meniere’s. They also question whether the swelling can actually cause vertigo.[ref]  Questions remain on what actually triggers Meniere’s.

Theories on the cause(s) of Meniere’s Disease:

The symptoms and progression of the disease vary a lot from person to person, making any single root cause of Meniere’s disease hard to pin down.

Some scientists postulate that Meniere’s is an autoimmune condition due to elevated antibody titers and higher levels of circulating immune complexes. People with autoimmune disease are also more likely to have more severe Meniere’s disease.[ref] [ref] Certain HLA serotypes are associated with increased risk of Meniere’s disease, adding to the evidence that it is autoimmune related.[ref]

Other researchers point to Meniere’s being multifactorial with causes including adrenal insufficiency, hypothyroidism, narrowing of the inner auditory canal, trauma, and allergies. [ref]

Genetic mutations and a familial aspect of Meniere’s disease is another line of investigation. [ref] The genetic variants linked with Meniere’s point towards the body’s immune and inflammatory response as well as potassium regulation.

All of these together point to a system that is out of balance.

Conditions that overlap with Meniere’s:

Meniere’s disease is linked to an increased risk of both migraines and motion sickness.[ref]

Migraine prevalence in Meniere’s is double that of the population in general. [ref]

People with rheumatoid arthritis are at a (slightly) increased risk of Meniere’s disease.[ref]

One study found that patients who didn’t respond to diuretics were more likely to respond to medications used to prevent migraines.[ref]

A study of 35 patients with Meniere’s disease found that 12 of them were clinically hypothyroid. Treating them with thyroid medication improved Meniere’s symptoms in all of the hypothyroid patients. [ref]

Allergies and histamine are also linked to Meniere’s

What if it is ‘just’ tinnitus and not Meniere’s?

Tinnitus is a sensation described as ‘ringing in the ears’ or a constant buzzing pitch.

In addition to being a symptom of Meniere’s disease, tinnitus can also accompany other hearing loss diseases or can occur spontaneously. It is thought to affect up to 15% of adults at some point in their life and affects both the quality of life and mental health.

Is tinnitus genetic?

Partly. Genetic variants do seem to play a role in the susceptibility to tinnitus, but environmental factors – such as lifestyle factors that cause inflammation – also are important here.

To determine whether a condition, such as tinnitus is ‘heritable’ or has a genetic component, researchers often study twins, siblings, and adoptees. In a large study in Sweden, researchers discovered that adoptees who had a biological parent with tinnitus were over twice as likely to have tinnitus. The researchers also noted no association between tinnitus in an adopted parent and adoptee, thus making the childhood environment an unlikely factor. [ref]

What causes tinnitus?

Researchers think that ion regulation – specifically potassium transport –  could be at the root of tinnitus.[ref] Other research points towards inflammation.

New studies using animal models of hearing impairment show that neuroinflammation may be a part of the picture for tinnitus and for hearing loss. Blocking TNF-α prevents neuroinflammation and tinnitus in a mouse model. [ref]

Other studies point to IL-1B (interleukin 1 beta), a proinflammatory cytokine, as being a risk factor.[ref]

Human studies show that inflammatory markers are important in tinnitus. A 2019 study in Portuguese adults found that IL10 was lower in tinnitus patients. IL-10 (interleukin 10) is an anti-inflammatory cytokine that limits your body’s inflammatory response. Thus low IL-10 could lead to higher inflammation. Accordingly, the researchers found that IL-1a, an inflammatory cytokine, was higher in participants with tonal tinnitus.[ref]

Salicylates and tinnitus:

To create tinnitus in animal research, the animals are often given sodium salicylate, which is the sodium salt of salicylic acid (aspirin). Higher doses of aspirin can cause (or worsen) tinnitus in some people.  Researchers have found in animals that salicylate blocks a certain type of calcium channel in the inner ear. This could then cause decreased GABA, an inhibitory neurotransmitter, in the inner ear.[ref]

The thought here is that not enough inhibition = constant firing of the neurons and tinnitus. GABA inhibits the excess firing, while glutamate can increase the neuron’s firing potential. Thus, alternatively, the salicylate could be increasing the firing rate of the neurons in the auditory nerve complex.[ref]


Genetic variants:

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The following genetic variants have been associated with Meniere’s or tinnitus in research studies. Note that a lot of the research is new, and hopefully there will be more research coming out in the future on both topics.

Meniere’s Disease Genes:

NFKB1 gene: codes for part of the nuclear factor-kappa beta (NF-κB) protein, which regulates inflammatory response. NF-κB is activated by cytokines and causes an increase in inflammatory markers.

Check your genetic data for rs3774937 (23andMe v4; AncestryDNA):

  • C/C: faster progression to hearing loss in Meniere’s [ref]
  • C/T: faster progression to hearing loss in Meniere’s
  • T/T: typical

Members: Your genotype for rs3774937 is .

Check your genetic data for rs4648011 (23andMe v4 only):

  • G/G: faster progression to hearing loss in Meniere’s [ref]
  • G/T: faster progression to hearing loss in Meniere’s
  • T/T: typical

Members: Your genotype for rs4648011 is .

Between Genes Region: An intergenic region that likely impacts tumor necrosis factor pathways and induces the translation of NF-kB.[ref]

Check your genetic data for rs4947296 (23andMe v4, v5; AncestryDNA):

  • C/C: 2-fold risk of Meniere’s, related to inflammation, higher NFKB1 levels [ref]
  • C/T: increased risk of Meniere’s
  • T/T: typical

Members: Your genotype for rs4947296 is .

KCNE1 gene: codes for a potassium channel protein that regulates the influx of potassium ions into a cell

Check your genetic data for rs1805127 (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • C/T: somewhat increased risk of Meniere’s (fairly common variant)
  • T/T: increased risk of Meniere’s disease[ref][ref] associated with kidney disease in Meniere’s patients[ref]

Members: Your genotype for rs1805127 is .

KCNE3 gene: another potassium channel protein

Check your genetic data for rs2270676 (23andMe v4, v5; AncestryDNA):

  • A/A: typical
  • A/G: somewhat increased risk of Meniere’s
  • G/G: increased risk of Meniere’s disease[ref]

Members: Your genotype for rs2270676 is .

Additionally, genetic variants in the histamine receptor 4 (HRH4) gene have been implicated in an increased risk of Meniere’s.[ref]

IL1A gene: codes for interleukin-1A, a proinflammatory cytokine that increases inflammation

Check your genetic data for rs1800587 -889C/T  (23andMe v4, v5; AncestryDNA):

  • A/A: typical
  • A/G: significantly increased risk of sudden sensorineural hearing loss
  • G/G: significantly increased risk of sudden sensorineural hearing loss[ref]

Members: Your genotype for rs1800587 is .

Tinnitus genes:

ADD1 gene: codes for the adductin-1 protein, which is important in blood pressure regulation

Check your genetic data for rs4961 G460W (23andMe v4, v5; AncestryDNA):

  • G/G: typical
  • G/T: increased risk of tinnitus. increased risk of hypertension
  • T/T: increased risk of tinnitus[ref], increased risk of hypertension[ref]

Members: Your genotype for rs4961 is .

IL1A gene: codes for interleukin-1A, a proinflammatory cytokine that increases inflammation  (NOTE – this overlaps with the IL1A variant in the Meniere’s genes section)

Check your genetic data for rs1800587  (23andMe v4, v5; AncestryDNA):

  • A/A: typical
  • A/G: somewhat increased risk of tinnitus
  • G/G: increased risk of tinnitus[ref]

Members: Your genotype for rs1800587 is .


Lifehacks:

Meniere’s disease lifehacks:

Modulating NF-κB (NFKB1 variants):
The genetic variants in the NFKB1 and the intergenic region show a definite link between NF-κB (nuclear factor – kappa beta) and Meniere’s disease for some people.

NF-κB is activated by cytokines such as TNFα and IL-1β. Thus, targeting inflammation may help with Meniere’s.

Mold has been shown in one study to trigger “a significant release of TNF-α in MD patients, which were not found in controls.” [ref]  Consider testing your home and workplace for mold.

Heat therapy, such as sauna, increases heat shock proteins. This increase in heat shock proteins then helps modulate inflammatory stress by decreasing the activation of NF-κB. [ref] Specifically, repeatedly activating heat shock protein 70 (Hsp70) leads “to the inactivation of downstream of nuclear factor-κB (NF-κB) inflammation signaling pathway.” [ref]

So is there any clinical evidence that sauna decreases the symptoms of Meniere’s disease? This doesn’t seem to be well studied. One case study from 1977 showed that sauna visits improved Meniere’s disease for the two participants. [ref]

Vitamin D deficiency and autoimmunity (everyone):
In people who are vitamin D deficient, increasing vitamin D through supplements or increased sun exposure may prove helpful for Meniere’s disease. Researchers theorize the improving vitamin D levels helps through modulating the immune response. Additionally, vitamin D deficiency doubles the risk for benign positional vertigo. For people who suspect that either inflammation or an autoimmune reaction is at the root of their Meniere’s disease, vitamin D is an easy solution to try, especially if you are deficient.[ref][ref][ref]

Cutting down on salt, caffeine, alcohol – maybe (KCNE1, KCNE3 variants):
Traditionally, patients have been encouraged to decrease or eliminate the consumption of salt, caffeine, and alcohol to improve Meniere’s symptoms. I think the idea here is that caffeine could cause vasoconstriction and that decreasing salt may decrease the fluid in the ear. [ref]

A recent Cochrane study concluded, though, that there is no evidence “from randomized controlled trials to support or refute the restriction of salt, caffeine or alcohol intake in patients with Ménière’s disease or syndrome.”[ref]

If you carry the genetic variants above in the KCNE1 and KCNE3 genes, these variants impact potassium transport across the cell membrane. Balancing out the potassium ions are sodium and chloride from table salt.  Even though there aren’t thorough randomized clinical trials to support restricting salt, this would be an easy lifestyle change to try. Experiment with altering your salt consumption – keeping track of both the amount of sodium you consume and your Meniere’s or tinnitus symptoms. Another experiment would be to track your potassium intake and see if it impacts symptoms.

The website and app cronometer.com is free and makes tracking sodium and potassium from foods really easy. You can also add notes there to track your symptoms.

Turkey Tail mushrooms (NFKB1, IL1A genes:
A study looked at the systemic effects of turkey tail mushroom extract (Coriolus versicolor) in relation to the oxidative stress and inflammatory response in people with Meniere’s disease. The turkey tail extract was found to increase Hsp70, sirt-1, and glutathione synthesis proteins, which should be helpful in Meniere’s. [ref]

Allergies (everyone):
Food allergies and inhalant allergies are common in people with Meniere’s disease. Interestingly, gliadin, a component of wheat, was found to often be an allergic trigger in people with Meniere’s.[ref] If you haven’t pursued allergy testing, this may be something to talk with your doctor about. Either avoiding an allergen or immunotherapy may help.

Thyroid (everyone):
If you suspect that you could have low thyroid function, talk with your doctor about getting your thyroid tested.  (You can also order the testing yourself in the US, but then you would still need to see a doctor if you need a prescription for thyroid medications.)  Research shows that reversing hypothyroidism can help with Meniere’s symptoms. [ref]

 

Lifehacks for tinnitus:

Melatonin as an antioxidant (IL1B and NFKB1 gene variants):
A clinical trial with 24 participants looked at the impact of supplemental melatonin on tinnitus. The results showed that 3mg/day of melatonin improved both sleep quality and tinnitus score. [ref] Another larger clinical trial compared melatonin to sertraline (Zoloft) and found that both statistically improved tinnitus, but that melatonin was more effective than sertraline. [ref]

One reason to assume that melatonin may be key here is that melatonin acts as an intracellular antioxidant, reducing inflammation and specifically reducing IL1A. [ref][ref]

If you want to try supplemental melatonin, a timed-release formula better mimics the body’s gradual release of melatonin throughout the night. Alternatively, you can block out light in the blue wavelengths (such as from TV, laptops, phones, and overhead lights) each evening before bed using glasses that block 100% of blue light. This has shown to increase overnight melatonin levels in most people.

Check your blood pressure (ADD1 gene variants):
Higher blood pressure at night has been found in people with tinnitus. [ref] Before you go to bed in the evening, check your blood pressure to see if it is elevated. If it is, talk with your doctor about your options for lowering blood pressure.

Trigger point therapy or acupressure (everyone):
A double-blind randomized clinical trial of patients with tinnitus and myofascial pain syndrome found that trigger point therapy was effective for the relief of tinnitus. [ref] Another study linked tinnitus to myofascial trigger points in the head, neck, and shoulders.[ref]

So where are the magic spots to push on to relieve tinnitus? Check out this article on ear acupressure points for tinnitus.

Improve your neck posture (everyone):
A case report details that 20 years of tinnitus for one patient was likely related to his neck posture. A cervical collar was the key for him, and it resolved the treatment-resistant tinnitus within weeks. [ref]  While a cervical collar may be an extreme way to go for most people, improving your posture may help. It seems like so many of us today have bent necks from looking at a computer or phone screen all the time.

Medications as a cause?
Check to see if any of your medications, especially NSAIDs and aspirin, could be adding to your tinnitus or vertigo.

There’s an app for that:
Researchers in 2016 used tailor-made notched music delivered through a phone app for 30-60 minutes per day. Added to that was a supplement of Ginkgo biloba. The combination was found to be effective for improving tinnitus scores. [ref]

Ginkgo Biloba has been studied fairly extensively for its effect on tinnitus. While a few studies show positive results, the majority of the studies show no real effect. [ref][ref]

Low-level laser therapy (LLLT) has shown in a study to be effective for reducing tinnitus in people with TMJ (jaw joint) problems. The LLLT was used at 1064 mn and 810 nm wavelengths. [ref]


Related articles and topics:

Mast Cells: MCAS, Genetics, and Solutions
Mast cells are an important part of your innate immune system. They are front line defenders against pathogens and allergens. For some people, mast cells can be triggered too easily, giving allergy-like responses to lots of different substances.

TNF-Alpha: Higher innate levels of this inflammatory cytokine
Do you feel like you are always dealing with inflammation? Joint pain, food sensitivity, etc? Perhaps you are genetically geared towards a higher inflammatory response. Tumor necrosis factor (TNF) is an inflammatory cytokine that acts as a signaling molecule in our immune system.



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.