Anosmia, by any other name…

The loss of the sense of smell (anosmia) is these days well-associated with COVID and Long-COVID, but also can simply come with age:

National Institute of Aging | How Smell & Taste Change With Age

…although it can also be something else entirely:

❝Another possibility is a problem with part of the nervous system responsible for smell.

Some studies have suggested that loss of smell could be an early sign of a neurodegenerative disease, such as Alzheimer’s or Parkinson’s disease.

However, a recent study of 1,430 people (average age about 80) showed that 76% of people with anosmia had normal cognitive function at the study’s end.❞

Read more: Harvard Health | Is it normal to lose my sense of smell as I age?

We’d love to look at and cite the paper that they cite, but they didn’t actually provide a source. We did find some others, though:

❝Olfactory capacity declines with aging, but increasing evidence shows that smell dysfunction is one of the early signs of prodromal neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.

The loss of smell is considered a clinical sign of early-stage disease and a marker of the disease’s progression and cognitive impairment.❞

~ Dr. Irene Fatuzzo et al.

Read more: Neurons, Nose, and Neurodegenerative Diseases: Olfactory Function and Cognitive Impairment

What’s clear is the association; what’s not clear is whether one worsens the other, and what causal role each might play. However, the researchers conclude that both ways are possible, including when there is another, third, underlying potential causal factor:

❝Ongoing studies on COVID-19 anosmia could reveal new molecular aspects unexplored in olfactory impairments due to neurodegenerative diseases, shedding a light on the validity of smell test predictivity of cognitive dementia.

The neuroepithelium might become a new translational research target (Neurons, Nose, and Neurodegenerative diseases) to investigate alternative approaches for intranasal therapy and the treatment of brain disorders. ❞

~ Ibid.

Another study explored the possible mechanisms of action, and found…

❝Olfactory impairment was significantly associated with increased likelihoods of MCI, amnestic MCI, and non-amnestic MCI.

In the subsamples, anosmia was significantly associated with higher plasma total tau and NfL concentrations, smaller hippocampal and entorhinal cortex volumes, and greater WMH volume, and marginally with lower AD-signature cortical thickness.

These results suggest that cerebral neurodegenerative and microvascular lesions are common neuropathologies linking anosmia with MCI in older adults❞

~ Dr. Yi Dong et al.

• MCI = Mild Cognitive Impairment
• NfL = Neurofilament Light [Chain]
• WMH = White Matter Hyperintensity
• AD =Alzheimer’s Disease

Read more: Anosmia, mild cognitive impairment, and biomarkers of brain aging in older adults

How to act on this information

You may be wondering, “this is fascinating and maybe even a little bit frightening, but how is this Saturday’s Life Hacks?”

We wanted to set up the “why” before getting to the “how”, because with a big enough “why”, it’s much easier to find the motivation to act on the “how”.

Test yourself

Or more conveniently, you and a partner/friend/relative can test each other.

Simply do like a “blind taste testing”, but for smell. Ideally these will be a range of simple and complex odors, and commercially available smell test kits will provide these, if you don’t want to make do with random items from your kitchen.

If you’d like to use a clinical diagnostic tool, you can check out:

Clinical assessment of patients with smell and taste disorders

…and especially, this really handy diagnostic flowchart:

Algorithm of evaluation of a patient who has olfactory loss

Train yourself

“Olfactory training” has been the got-to for helping people to regain their sense of smell after losing it due to COVID.

In simple terms, this means simply trying to smell things that “should” have a distinctive odor, and gradually working up one’s repertoire of what one can smell.

You can get some great tips here:

AbScent | Useful Insights Into Smell Training

Hack your training

An extra trick was researched deeply in a recent study which found that multisensory integration helped a) initially regain the ability to smell things and b) maintain that ability later without the cross-sensory input.

What that means: you will more likely be able to smell lemon while viewing the color yellow, and most likely of all to be able to smell lemon while actually holding and looking at a slice of lemon. Having done this, you’re more likely to be able to smell (and distinguish) the odor of lemon later in a blind smell test.

In other words: with this method, you may be able to cut out many months of frustration of trying and failing to smell something, and skip straight to the “re-adding specific smells to my brain’s olfactory database” bit.

Read the study: Olfactory training: effects of multisensory integration, attention towards odors and physical activity

Or if you prefer, here’s a pop-science article based on that:

One in twenty people has no sense of smell—here’s how they might get it back

Take care!

First introduced as a diabetes medication, GLP-1 drugs quickly took hold for off-label use as weight loss aids, even when the science was still very young.

Here’s one of our first articles on that, back in the day: Semaglutide’s Surprisingly Big Research Gap

As for that popularity? Check out: 1 in 5 US Women Aged 50–64 Has Used GLP-1 RAs: What We’ve Learned

Spoiler, one of the things we’ve learned is: Most People Who Start GLP-1 RAs Quit Them Within A Year (Here’s Why)

One of the main things in their favor is, of course, that (for most people, anyway), they work (except when they don’t: Why Intermittent Fasting (& GLP-1 Drugs!) Might Not Work For You).

In other words, a rocky road with pros and cons. But today, let’s talk about the question many have been asking:

Does it come in a pill?

Most people don’t love injections, and GLP-1 drugs being injection-only for these past years has not been simply because the drug companies like to be annoying.

In fact, there are often technical challenges with making a drug work by different routes of administration, for example:

• Skincare products are usually not best taken rectally
• It’s hard to make a gut-repair drug that can be taken as a transdermal skin cream
• And so on

For this reason, subcutaneous injections have worked as a way of delivering drugs to agonize GLP-1 receptors, in ways it’s been hard to do with a pill that has to get past stomach acid and your gut barrier, before getting into your bloodstream.

However! Most recently, researchers (Dr. Vanita Aroda et al.) tested elecoglipron, a once-daily oral GLP-1 receptor agonist for type 2 diabetes, in a sizeable trial involving 406 participants across 9 countries.

Unlike most GLP-1 drugs, elecoglipron is a non-peptide tablet taken once daily with no food or fluid restrictions, making treatment much more convenient.

In numbers:

• Before starting: the average participant was 58.4 years old, weighed 99.8 kg, had a BMI of 34.9 kg/m², and started with an HbA1c of 7.9%.
• Blood sugar results: after 26 weeks, HbA1c fell by 0.91 to 1.88 percentage points depending on dose, compared with a 0.15 percentage-point reduction in the placebo group.
• HbA1c results: up to 89.6% of participants receiving elecoglipron reached an HbA1c of 7% or below, compared with 24.9% of those receiving placebo.
• Weight loss results: up to 72.3% of participants taking elecoglipron lost at least 5% of their body weight, compared with 20.2% in the placebo group.
• Side effects: adverse events occurred in 63% to 87% of participants across the elecoglipron groups versus 63% with placebo, with the most common being nausea, constipation, diarrhoea, and vomiting. This sounds bad, and by itself it is, but it’s worth noting that the drug’s safety and tolerability were generally consistent with other GLP-1 receptor agonists. So in other words, in terms of adverse effects it’s very comparable to Ozempic, Wegovy, Mounjaro, and all the others of that ilk.

In other words: it works! Very comparable to other GLP-1 RAs. Same drug-related drawbacks, just without the needles.

You can find the paper itself, here: Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with type 2 diabetes (SOLSTICE): a multicentre, phase 2b, randomised, placebo-controlled trial

Want to learn more?

You might also like this book that we reviewed a little while back:

Magic Pill: The Extraordinary Benefits and Disturbing Risks of the New Weight-Loss Drugs – by Johann Hari

Take care!