Finding a talisman

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Experiential observations and anecdotal insights from the patient community have generated many key discoveries for the field of Parkinson’s research. A chance question (“Why do people with Parkinson’s smell different?” – click here to read more about that) or random interaction have opened doors to entirely new realms of research.

An good example of this are numerous reports of symptomatic relief at high altitudes. Some people with Parkinson’s find that when they are above a certain altitude, they are almost symptom free.

The mechanism of this phenomenon is unknown, but a new study in the Netherlands is hoping to help us better understand it.

In today’s post, we will discuss the Talisman study.

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Source: theplanetd

The Kingdom of Bhutan is a landlocked nation of 755,000 people in the Eastern Himalayas. It is embedded in the mountainous region between China and India, and it is one of the highest countries in the world – sitting at an average land elevation of 10,760 feet above sea level (Source).

Source: Koryogroup

Interesting facts about Bhutan (Source):

  1. Bhutan was the first country in the world to have specific constitutional obligations on its people to protect the environment. Among the requirements, at least 60% of the nation must remain under forest cover at all times.
  2. One-third of Bhutan’s population is under the age of 14 (its median age is 22.3 years).
  3. It is the only nation in the world where the sale of tobacco is completely banned.
  4. The capital (and largest) city, Thimpu (pop.: 114, 551), does not have a single traffic light.
  5. It was one of the last countries in the world to introduce television. The government lifted a ban on TV—and on the Internet—in 1999.

Interesting, but what does any of this have to do with Parkinson’s?

In 2009, the actor and Parkinson’s advocate Michael J Fox was visiting Bhutan and he noticed something rather interesting.

To me, hope is informed optimism” – Michael J Fox (Source)

As the Parkinson’s community are well aware, Michael was diagnosed with the condition in 1991, and went on to form the Michael J Fox Foundation with the goal of curing the disease.

He also continued his film and acting career, which took him to Bhutan when he was filming the ABC show “Adventures of an Incurable Optimist” in 2009.

Curiously, while he was in Bhutan, he noticed that his Parkinson’s symptoms disappeared.

He said that “by the third day, he hadn’t had to take his meds as much, and even climbed a mountain” (Source). He has shared this experience in different interviews (Click here to read more about this), and others with Parkinson’s have also noticed something strange happens with their symptoms when they are at altitude.

Michael in Bhutan. Source: Macmillan

Fred Ransdell, the author of Shaky Man Walking, has described two situations where his Parkinson’s-related tremors almost completely disappears:

  1. When he was driving over mountain passes at 9,000 feet elevation, he noticed that at that moment his tremors were disappeared.
  2. Whenever he is flying on commercial airliners (Most aircraft cabins are pressurized to an altitude of 8,000 feet – Source). Fred has said while the plane remains at altitude he is completely asymptomatic until the plane lands.

Source: Honeywell

Wow, this is weird. How does this effect work?

We do not know.

There are a number of theories – from changing the pH of our blood (due to breathing out more carbon dioxide at high altitudes) to how intermittent hypoxia increases dopamine synthesis (Click here to read more about these theories).

The short answer, however, is: We don’t know.

To remedy this situation and improve our understanding, the Michael J Fox Foundation has funded a study to investigate this phenomenon further (Source).

It is called the TALISMAN study.

The study is being conducted by a team of researchers in the Netherlands being led by Prof Bas Bloem:

Prof Bas Bloem. Source: Claudiabouwens

The research team who will be artificially inducing a low oxygen environment to see if it has any impact on the symptoms of 25 people with Parkinson’s. Specifically, they will be using a commercially available hypoxicator, and varying concentrations of oxygen (administered via a tight-fitting oxygen mask) to simulate different altitudes.

There will be 5 conditions tested:

  1. Intermittently delivery of 16.3% O2 or room-air, each for 5 minutes, for 5 cycles per session (16.3% will simulate 2000 meters)
  2. Intermittently delivery of 12.7% O2 or room-air, each for 5 minutes, for 5 cycles per session (12.7% will simulate 4000 meters)
  3. Continuous delivery of 16.3% O2 or room-air, each for 45 minutes
  4. Continuous delivery of 12.7% O2 or room-air, each for 45 minutes
  5. Continuous delivery of for 45 minutes, at sea level (20.9% O2)

The researchers will be using an N-of-1 study design in this project.

What does that mean? N-of-1?

N-of-1 studies focus on observing changes in a single individual/participant in a study over time, rather than looking for changes in the average response of groups of participants. The design of the trial is around testing a treatment on one person.

How is this achieved? How can a treatment be assessed on a single individual?

N-of-1 studies typically involve cross-over treatment regimes, in which the participant is randomly and blindly shifted from one treatment to another over time.

This is what a typical N-of-1 study design may look like:

Source: Researchgate

In this study, over 18 days the individual participant will be randomly exposed to three different periods of treatment.

And the beauty of this approach is that numerous N-of-1 studies can be conducted in parallel and the individual results of each study can be pooled in post hoc analysis, so that the researchers can look at group differences.

Here at SoPD HQ, we are VERY keen on this type of study design. A lot of research ‘talks-the-talk’ about “personalising” medicine, but only N-of-1 studies really approach the topic properly. Look out for more on N-of-1 research on the SoPD in future, and in the mean time – those interested in reading more about this should click here).

So there will be 25 participants in the TALISMAN study, but they will each be doing an N-of-1 study?


The Talisman study is ongoing at the moment and it will hopefully be completed in February 2023 (Click here to read more about this study).

I have heard things about something called hyperbaric oxygen therapy. Is this Talisman project related to that?

Hyperbaric oxygen therapy chamber involves the air pressure being increased two to three times higher than normal air pressure. This is different to the low oxygen approach that the talisman study is exploring.

As far as I am aware (and I am happy to be corrected on this) there has been very limited clinical research on hyperbaric therapy in Parkinson’s. There was one case study of an individual with Parkinson’s who also suffered severe depression and anxiety who was treated with hyperbaric therapy (Click here to read that report), but I have not heard of much else.

So what does it all mean?

The word talisman is ancient.

It has been passed between languages over the ages. It comes from the French word talisman, via the Arabic word ṭilasm (طِلَسْم, plural طلاسم ṭalāsim), which itself stems from the ancient Greek telesma (τέλεσμα), and ultimately from the verb teleō (τελέω). It means “I complete, perform a rite” (Source). It seems like a nice name for a study whose origins began with the climbing up of mountains.

I like a good story and the tale behind the talisman study is an interesting one. Anecdotal evidence for patient experience has pointed researchers towards high altitude factors as having an impact on Parkinson’s symptoms. Why this is, we are still trying to work out, but it will be interesting to see if these curious effects on PD can be artificially recreated in the clinic.

It will also be interesting to see the utility of the N-of-1 study design in the talisman study. There is no such thing as “an average patient” so why we continue to take the easy path and conduct clinical trials focused on such ideas is confounding. The more personal we can make each study, the closer we get to actually helping each patient with their specific Parkinson’s.

Like I said, look for more on N-of-1 on the SoPD going forward.


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13 thoughts on “Finding a talisman

  1. I wonder whether anyone has investigated the incidence of Parkinson’s in high vs low altitude populations.
    It would be interesting to invert the scenario that Michael J Fox experienced; take someone with Parkinson’s who lives at high altitude and see how their symptoms are at low altitude.


    1. I’m living at 7k in elevation and spent a week with my kids in Minneapolis. No difference noted, except that I had much better stamina!


  2. We visited Peru a few years ago, and husband’s PD was significantly worse at altitude; it was the first time he had really suffered. I thought at the time that it pointed to a link with oxygen. I’ve mentioned it to researchers on a number of occasions, but no one has agreed with me. So it’s good to hear that some research into pd and altitude is happening.


  3. Most intriguing. It makes you wonder how on earth this would work. You get the feeling that haemoglobin is involved somehow, what with its intimate involvement with dioxygen. Question: are Bhutan natives PD-free?


  4. Hello Simon,
    I’m yopd diagnosed 1.5 years ago at 33 and I experience this phenomenon everytime I travel or am at high altitudes. I think we are thinking zebras when we hear hoofs. My personal experience suggests this may be related to lower atmospheric pressure at higher altitudes. A potential effect of lower pressure/forces on the body, specifically the cranium. I’m an engineer by trade and have over analyzed this phenomenon more than your average person. This is my most convincing conclusion as an n of 1.

    Liked by 1 person

  5. Yes, like tigri1988 I was thinking that oxygen is just one variable, and pressure would be another. Air at higher altitudes also tends to be more pure. And Bhutan is a very special place, where the society and environment could be very relaxing, which might also influence the results. Interesting also that tigri1988 is young onset, and so is Michael Fox.


  6. Interesting… I live at 7000′ and frequently camp and hike at higher elevations – 10k and above. Haven’t noticed a difference, but then again I’m cheating a bit – had DBS last year, and now take no meds. I’m very much at peace in the mountains, wonder if that’s a factor?


  7. Is it possible that there is a link with the ionization of the air or magnetic fields?
    Both conditions exist in airplanes in flight and in mountains.


  8. Hyperbaric oxygen. I have been taking this treatment for a couple of years now ; the main effect is on brain fog which it disperses. It is more widely used in MS patients. [ I have PSP,, an atypical parkinsonism]. Keith


  9. Transient Relief Only? A key question not directly discussed above: Is the relief in syptoms merely transient? Put another way: If I move to Leadville or Katmandu and stay there for a long time (many years), will the relief in symptoms last 3 hours, three days, or 30 years?

    Let me suggest another hypothesis: Nitrogen Low Partial Pressures.
    If I scuba dive to 120 feet on a normal air (20/80 oxygen/nitrogen), I will feel so happy that I offer to share my mouthpiece with my good friends the fishies, for
    it is well known that Nitrogen becomes a narcotic at high partial pressures. So contrary to rational expectations, the poor mans’s noble gas, has real effects on the brain. This leads to the question: What effect on our brains would low partial nitrogen pressures have? Perhaps we need to put some Parkinson’s patients on the standard deep-diving 20/80 oxygen/helium mix, and review any changes in symptoms.


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