Review: Can Post-Exertional Malaise make a Placebo Effect seem like a Nocebo?

Introduction

I recently participated in the Mendus Mitoq study and this is a personal case-study style write-up of my experience. In this post I attempt to interpret my placebo/nocebo effects but make no attempt to represent a standard participant in the study (my reaction wasn’t typical).

Thinking through the nature of placebo effects seems particularly important for us as people with conditions like ME. The contested nature of our disability makes it useful to understand that people with any illness will get placebo effects (although how the placebo effect works varies between types of symptoms). It doesn’t indicate that the underlying problem is “all in the mind”. Since placebos can affect physical healing, while we are waiting for a specific treatment that works, it may be pragmatic to harness any placebo benefit we can grab hold of.

However, we should guard against being fobbed off with treatments which are essentially just placebos. Many other conditions which are less common get good quality, rigorous research leading to specific treatments (giving extra therapeutic effect on top of placebo effects). We should expect equality in this.

ME is also a complex, fluctuating, multi-systemic disease. This makes it particularly complicated to recognise cause and effect when we try new approaches. A placebo tablet is a useful tool to tease out genuine effects of a treatment. Placebo controlled experiments like this one indicate some degree of scientific rigor and a way to measure how specifically useful a treatment is (and if it is worth the cost or risk).

But what is it like to take part in a placebo controlled experiment? That is the topic of this post.

Contents

What is Mendus?

Mendus does patient-led research usually combining quantified-self results. It cuts down the need to wait for official research and funding and enables us to find out what might work for us as individuals. The Mitoq trial was a bit different from previous studies:

“The MitoQ study is by far our largest to date. This is because it was sponsored by the manufacturer who supplied over a hundred people with their product for free to evaluate for ME/CFS and Fibromyalgia. We were able to implement an impressive crossover, placebo controlled, double blind design. That is, everyone receives both placebo and MitoQ and no one knows which is which until after the study…

[Mendus is] trying to publish the results of the MitoQ Study and until we know whether that will happen the overall group results will not be revealed. This is because the scientific journals would be less likely to accept our report if the results had already been made public.” Mendus

What is Mitoq?

I’ve previously written about mitochondria issues on this blog as it seems like an important aspect of ME. Mitochondria generate energy in cells, they are often called cell powerhouses. We seem to have some problems with our mitochondria although it is unclear whether this is at the level of it being a mitochondrial Disease or just dysfunction.

“Both fibromyalgia (FM) and myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) have been associated with oxidative stress as well as mitochondria dysfunction (1, 2). Coenzyme Q10 is a natural antioxidant that combats oxidative stress and also plays a critical role in energy production within mitochondria. Theoretically, the substance is in a good position to help symptoms of both FM and ME/CFS. Indeed, several studies have shown functional and symptomatic improvement in these disorders following coenzyme Q10 treatment (1-3). There has been significant advancement in tailoring the Q10 molecule to enhance its effectiveness. Mitoquinone or ‘MitoQ’ is one such product that has been extensively studied (4). MitoQ is a charged form of coenzyme Q10. A small change made to the molecule results in a positive charge.

Mitochondria, where the molecules are needed, have negatively charged membranes. The result is that MitoQ is more strongly attracted to the mitochondria and taken up more readily (4).” Mendus

Explanation of Research Terms

This is a quick bluffer’s guide to relevant terminology (or you can skip to my diary instead):

Confounding Variables

These are other things which vary unintentionally during the experiment and may confuse results. There are always confounding factors in experiments like this and you can only control so much. For example, people eat different things, catch a virus, go to bed at different times, have to change other medication.

Placebo Tablets

The most studied treatment is in fact a placebo tablet because they are used as a control in so many experiments. In this study we took tablets from two different bottles. One of the bottles contained placebo tablets which were exactly the same as the other bottle, except they didn’t contain the active ingredient MitoQ (the other additives were the same and they looked identical). The experiment was double blinded which means that neither the participants nor Josh knew the order of the bottles. The manufacturer also randomised the order so that some participants had Mitoq in Bottle 1 and others had the MitoQ in Bottle 2 (they took it after the Placebo tablets). At the end Josh could look up a record and tell me which order I had taken them in.

Placebo Effect

The reason it is a good idea to have placebo tablets is that just taking any tablet or treatment can lead you to interpret symptoms differently, or even create measurable biological changes which are nothing to do with the specific mechanism of the treatment. Your expectations or conditioning about a treatment can change your health.

“Some placebo responses, such as analgesia, are initiated and maintained by expectations of symptom change and changes in motivation/emotions. Placebo factors have neurobiological underpinnings and actual effects on the brain and body. They are not just response biases. Other placebo responses result from less conscious processes, such as classical conditioning in the case of immune, hormonal, and respiratory functions.” (5)

Everyone in the study took the placebo tablets but Placebo Effects are changes which can be attributed to taking any tablet rather to taking Mitoq (some people wouldn’t get Placebo Effects). The Placebo Effect influences about 1 in 3 people.

Simplistically, the Mitoq results minus the Placebo results should give you the real efficacy of Mitoq. However, there are some complications, such as order effects, which you can see in my diary below.

I’ve read different conclusions about whether people have a tendency to the Placebo Effect. Some say whether you get a Placebo Effect with one treatment doesn’t mean you can predict if the same person will get it again (ie it’s not a personality thing). I’ve also read that being agreeable, extrovert and open to new experiences (psychological traits) are good predictors and there can be a genetic aspect to it.

“So far, the 11 genes implicated in placebo response are all involved in known neurotransmitter pathways. One example is a common mutation in the COMT gene, which encodes an enzyme that breaks down the hormone dopamine. As many as a quarter of Caucasians carry two copies of the mutated gene, which results in higher levels of dopamine. In 2012, Hall and her colleagues showed that having two copies is associated with a stronger placebo response in people suffering from irritable bowel syndrome.” (6)

 

weird things about the placebo effect:

1. It doesn’t have to be a secret. Some believe that a placebo can only work if the recipient is unaware they are taking one. But there’s evidence that people with irritable bowel syndrome who knowingly receive a placebo do better than those who are left untreated.

2. It works better if it’s expensive. The pain-killing power of a placebo pill is greater among people who are told they are taking a full-price version, compared to those told that the pill is on sale for a discounted price.

3. It’s not just us, animals can get it too. A 2012 study found that between 30 and 40 per cent of rats experienced pain relief when their morphine injections were swapped for inactive saline solution.” (6)

Nocebo Effect

The Placebo Effect seems like a Generally Good Thing. Ideally you want to add in some medication that has a specific and efficient therapeutic effect on top, but the news that your brain can trick you into feeling better/ actually healing seems like something to take advantage of.

The flip side of the Placebo is the Nocebo Effect. In Latin this means “I shall harm”. It is the same type of thing as the Placebo Effect but makes you feel worse and is less well understood. It is probably how Voodoo magic takes effect. Nocebo effects can be seen on brain scans – when a person expects to feel more pain the pain can be seen to be more intense. Dopamine and endogenous opioids (natural painkiller) are reduced under the Nocebo Effect (7). No genetic link has been demonstrated yet with Nocebo.

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Diary

This section is a diary I kept at the time I was doing the trial. When I wrote it I had no idea which bottle was the placebo. My words are unedited but some bold emphasis is with the benefit of hindsight to make it easier for you to skim read the bold bits if you prefer.

During the study we all supplied quantitative data for symptom scores and cognitive tests. The cognitive tests are from Cambridge Brain Sciences and you can try them out too. We did Digit Span to assess Working/Short term Memory, a spot the difference called Polygons for Concentration and Grammatical Reasoning to get a sense of our Reasoning ability. Before starting the first bottle we gave baseline scores for the tests and our symptoms. Graphs for my scores are in the footnotes for your information.

Bottle 1 (Contents Unknown)

Day 7

I’m hoping that the first pills are placebo because I’ve not had a particularly good week. This was hard to sum up quantitatively on the form because it has been up and down. The first half of the week was average, then I went out on Wednesday and did more than usual which I enjoyed. On Friday I was really bad after a shower, hardly able to lift myself up in bed and felt relapse level. It wasn’t clear whether this was PEM from Wednesday or an immediate POTS reaction from the shower, possibly a bit of both. It doesn’t feel like side effects anyway. I’ve been lying down most of the time since then.

I feel foggy today but the [online cognitive] test results are a mixed bag. I improved a little on the digit span test [memory test], but from doing this before for D-ribose I think I get practice effects for that. I found the polygon [concentration] test much harder than last week [baseline]. There was a qualitative difference like I lacked oomph (less adrenaline or similar) and I wasn’t able to do it quickly. I also found it hard to notice the differences between shapes. On the other hand, I found the grammatical [online reasoning test] easier, the answers seemed obvious and I just plodded through it getting every answer correct (but again I was quite slow in my response rate so only got 56%).

I think my other supplements are the same. For example, this morning I had caffeinated coffee with d-ribose, which from memory was the same last week. I didn’t sleep well which could be enough in itself to account for mental fogginess.

 

Day 14

This week I committed a major participant faux pas and started a new medication. In an ideal world I would eat similar food, take the same supplements and medication for the whole 12 weeks to try to control other factors as much as possible. However, my POTS doctor wants me to try a new drug (ivabradine) to control my heart rate better. This doesn’t seem like it would interfere too much with the effects of CoQ10 as the effect is specific to lowering heart rate (and I already take beta blockers to do this but I couldn’t tolerate a higher dose due to low blood pressure). I feel bad starting it a week into Bottle 1 but the alternative is to get tachycardia standing up for the next 11 weeks when I don’t need to.

[I later provided additional scores as a 2nd baseline and extra scores taking bottle 1 and ivabradine as a comparison for Day 7]

Ivabradine may have effected my subjective symptom ratings a little this week but it doesn’t seem to have impacted the cognitive tests. My grammatical reasoning seems to be generally good and the score this week of 56 is inbetween my best score of a baseline 80 and last week’s 41. Digit Span was 7 again, in my opinion I’ve learnt how to do this and then plateaued (I’ve also done this for another Mendus study and as a psychology student). My polygon score was 17 which was the same as the baseline measure and top of the Bell Curve for the general population scores.

Generally I’m pleased with the cognitive scores I’m getting because they are average/above average. A couple of years ago I had a really hard time reading or following TV storylines, and I wasn’t functioning at an average level. Also at university I had to do cognitive tests for other people’s experiments (to get credits) and after I had glandular fever I tended to do badly and be excluded as an extreme outlier. It feels good to be averagely intelligent again although I’m not sure how fatigue relates to the tests. I definitely feel temporary ME cognitive fatigue after doing the tests and wouldn’t be able to do them repeatedly. [in other words if anyone from the DWP is reading, this doesn’t mean I can predictably sustain cognitive tasks!]

 

Day 28

I forgot to do the tests at noon and did them at 3.30pm. I generally try to do them at the same time of day because I think time of day effects may be greater than the benefit of the Mitoq. I do the tests after a caffeine drink with d-ribose in as that was something I was already doing in the morning and would be likely to change the results if I change it. The afternoon is the best time for me.

Something I’m noticing with the cognitive tests is that my perception of fogginess doesn’t match well with my actual cognitive ability on any given day (which may have relevance for other trials which relied purely on subjective measures, not mentioning any in particular...). Today I feel quite groggy compared to an otherwise good week. I did relatively well on the tests though. On the Polygons test I scored 94 and only 5% of people score higher than that. The answers felt more obvious. I found it easy to follow the Grammatical Reasoning task, getting all the answers right again, I’m just held back by thinking a little slowly. On Digit Span I got 7 again, and the normal range is 7+/-2 so that is normal. It also feels like a genuine plateau, I can keep 7 numbers in my head but as soon as I try 8 they all get jumbled up.

Inline image 1

(the first two of these scores were before the baseline, when I was finding out about the site, worth mentioning as I did much worse on the day of the baseline)

Inline image 2

I find the subjective symptom scores hard to fill out for a whole week. My symptoms do vary quite a bit, so averaged out I don’t think this has the level of meaning that it did in the Diet Study when you complete the scales everyday.

This week was noticeably more active overall for me (which is very relative of course compared to most people!). I was able to engage in craft activities for much longer than normal. I feel I can hold my head up more easily (often I need to lean my head on something). I do feel some PEM from going out yesterday. Since I started Ivabradine recently it will only be the comparison with Bottle 2 which will show if this is likely to be to do with Mitoq. I’ve had to vary my Ivabradine dose due to being woken in the night by throat constriction. This is a variable I hadn’t anticipated. It is probably an allergy to something else as I don’t get it every night and I take Bottle 1, bisoprolol and ivabradine everyday.

 

Middle Week

I’m at the week of taking neither bottle so that Bottle 1 gets out of my system.

At the moment I’d go with placebo for bottle 1.

I didn’t get any side effects starting bottle 1 which is unusual for me. I’ve also confused it with starting ivabradine after the first week so my opinion won’t mean much at this point. Effects I’m attributing to ivabradine and not bottle 1: lowered heart rate, a bit less orthostatic intolerance, deeper sleep. These haven’t gone yet in my in between week.

I find the psychology of a placebo interesting. I think I’m generally inclined to want the 1st condition to be placebo because I don’t suddenly feel well. This would apply to anything non-miraculous! I noticed it on the d ribose even though it was actually 1st and seemed to help pain when I looked back at the results.

Today I did an extra baseline, as my original baseline was before I started Ivabradine. Josh is also going to interpolate my first week on Bottle 1 scores as they were pre-Ivabradine (plus I did an extra set of scores on Bottle 1 to compare this to).

 

Bottle 2

Day 2

I would be surprised if this wasn’t the Mitoq. It does seem to have an effect on me but not all good. Yesterday I was able to concentrate at a much healthier level all afternoon, achieving quite a lot. I am too ill to work so this is unusual. However, physically I felt worse in a POTS low blood pressure/vasodilation type of way. After a morning shower my limbs were heavy. In the early evening I had a spell of feeling really nauseous and hot. This was relieved by lying down for a couple of hours. I then had a bad night with racing nonanxious thoughts, stomach discomfort and funny perception of temperature. It isn’t the type of feeling I normally get.

I’m hoping that the initial dose is just too high. Usually I titrate everything slowly. Tomorrow I might just take a bit of the powder from one of the tablets.

 

Day 7

Unfortunately I’ve had a flare up all week. Maybe coincidence but feel I need to pause bottle 2 a week to see what’s what. Am I right in thinking it doesn’t actually accumulate over time? I did 2 days full tablet pre breakfast. Both nights bad insomnia. Then I tried with food which was better but still awake quite a bit. Then half the tablet with food and then 1/4 but I wasn’t feeling better (though could sleep at that point). Got fever, neck pain and brain too large for skull sensation, bad enough to stay in bed (a symptom cluster I’ve had before). This could be separate virus which happened to start on day 1 of bottle 2 but I haven’t had sore throat and noone else is ill. My hunch is 20mg is too strong for me, over stimulating/shock to system. This led to insomnia which in turn led to a ME flare up (fever etc not direct side effect).

My symptoms were generally worse. I haven’t properly followed protocol and don’t feel up to getting up to do cognitive tests today so haven’t filled in form.

These would be my ratings:

Pain 8
Energy 2
Clarity 4
Sleep 1
Depression 7
Gastro 7
Overall 2
Active 3

I don’t want to pull out completely because I did get a glimpse of being able to concentrate longer on the first day. I think I just need a dose low enough to avoid insomnia because that’s counterproductive. I feel bad about not following the instructions but I guess this type of issue is partly what the study is about.

I’ll pause a week hopefully returning to baseline. I’ve improved this afternoon so that should be possible. Then I can restart taking after breakfast and taking some of the powder out. If I tolerate that fine I’ll build up to the full tablet before breakfast. That’s normally how I’d start a new supplement.

If I’m wrong and it’s the placebo I probably won’t react again because whatever the other factor is should be gone. Unless I get some sort of reverse [nocebo] placebo effect…

 

Day 21 (sort of)

 I’ve taken Bottle 2 again for 7 days but only 1/2 tablet after breakfast (presumably 10mg or thereabout). I get the same over stimulated feeling with insomnia. In the week I had off I returned to feeling like base rate measures. I’ll be intrigued if this is a nocebo effect.

Having tried again I think I do need to pull out. I think in a different illness phase it could be helpful.

 I’ve not filled in the standard form because I deviated from the main protocol (but emailed this to Josh).

 Symptoms

Pain 8

Energy 3 (tired but wired mentally, physically drained and heavy)

Clarity 8

Sleep 2 (lack of sleep probably accounts for other symptoms which are worse)

Depression 1 (if good, forgetting direction!)

Gastro 8

Overall 4

Active 2

In terms of a qualitative description of how I feel:

The positive side is that I feel much more mentally creative with an excited energy which isn’t captured well in the tests and symptom scales apart from wiping out depressive thoughts (I don’t suffer from clinical depression). This tips over a healthy balance though and I can’t switch off new ideas, beyond the edge of my usual cognitive/affective experience. I feel mentally over stimulated a bit like drinking too much coffee, although the physical sensation isn’t the same as caffeine. It is probably a Speed equivalent but I’ve never taken that. This results in insomnia which in turn is generally bad for other ME symptoms (constant headaches, gastro disruption, slightly feverish).  It is also as if the energy directed at thinking is at the expense of physical movement. I have spent more daytime hours in bed. A direct comparison is that I struggled to get up today to do the tests at midday and the first week of Bottle 2 I didn’t get up at all on Day 7. The other weeks it was quite routine to be up at that time. I have the desire to lie down but constantly occupy my mind (lying in bed going online). 

My impression is that this effect could be good if I was in a phase where my cognitive function was worse than my physical stamina. However, at the moment my cognitive ability is much better than comparative physical symptoms. For example, I’m still limited in how long I can sit upright and standing/walking is brief and around the house only but I can concentrate and can usually spend most of the day online. Bottle 2 seems to exaggerate the cognitive/physical difference.

Cognitive Tests

Digit: 7

Grammatical: 22

Polygon: 74

Digit span – 7 again but I may have been slightly better as it showed me more 8 digit sequences, I definitely couldn’t remember those. On the Grammatical Reasoning I generally get each answer correct so speed of processing is only limitation and results are fairly stable. The first half of the Polygon test differences seemed more obvious initially this time and then I had a mini confidence crisis and got several wrong in a row.

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Interpretation

Which way around do you think the bottles were? The first bottle was actually MitoQ, so I pulled out of an experiment due to side effects during the placebo phase! Despite being aware of placebo and nocebo effects I was still susceptible to the worst type of outcome. My first emotional reaction was to feel embarrassed and gullible, although I know it’s normal.

At first glance it seems to be a case of nocebo effect rather than placebo. However, I think there are a few things to think about.

Confounding factors? 

  • I started Ivabradine for POTS (which is usually for angina and has an amber warning). It can take a while to completely take effect.  Also, I stopped taking supplements like melatonin and valerian at night in case they caused bradycardia with the Ivabradine, which is something I’ve only just remembered. The mental over stimulation sensation and insomnia went in the week I stopped Bottle 2 and I felt generally calm that week, so it seems unlikely that this is a complete explanation.

  • Christmas is turbulent for emotions and routine and Bottle 2 started just before Christmas. However, I usually feel down at New Year and felt the opposite this year. Christmas itself was calm (the week I paused Bottle 2) but a bit stressful in the buildup.

  • Perhaps I happened to have genuinely exciting, sleep depriving ideas both times I tried Bottle 2! I think this could apply to the 2nd attempt but the 1st attempt I only got excited because I thought I could do a task I wouldn’t normally attempt.

  • The initial reaction to Bottle 2 could have been symptoms of MitoQ withdrawal from finishing Bottle 1. This doesn’t seem very likely though as I felt alright in the middle week inbetween the two bottles.

  • There are many other possibilities such as catching a virus. Returning to baseline in the Bottle 2 pause week does seem to indicate some placebo/nocebo effect though.

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Nocebo Effect?

Before taking these tablets I’d come to the conclusion that Bottle 1 was placebo so that may have primed me to expect side effects for Bottle 2 (nocebo effect). I even comment in the middle week that because I didn’t get side effects Bottle 1 must be a placebo. This indicates that I have a belief that therapeutic benefits come with additional side effects, which will be something I challenge in the future.

Nocebo could be interesting in ME because we seem prone to getting side effects when we start supplements and medication. I do believe that there is some biological basis to this, but it may be that once we have had side effects once, we are then susceptible to expect the worst when we start something new. This could be undermining potentially effective treatment, or just subjecting ourselves to nasty nocebo when we could be basking in sunshiney placebo effects.

There may be ways to guard against nocebo. For example if medical staff trigger these types of negative suggestions, challenge them in your mind:

● “Causing uncertainty “This medication may help.” “Let’s try this drug.” “Try to take your meds regularly.”

● Jargon “We’re wiring you up now.” (connection to the monitoring device) “Then we’ll cut you into lots of thin slices.” (computed tomography) “Now we’re hooking you up to the artificial nose.” (attaching an oxygen mask) “We looked for metastases—the result was negative.”

● Ambiguity “We’ll just finish you off.” (preparation for surgery) “We’re putting you to sleep now, it’ll soon be all over.” (induction of anesthesia) “I’ll just fetch something from the ‘poison cabinet’ (secure storage for anesthetics), then we can start.”

● Emphasizing the negative “You are a high-risk patient.” “That always hurts a lot.” “You must strictly avoid lifting heavy objects—you don’t want to end up paralyzed.” “Your spinal canal is very narrow—the spinal cord is being compressed.”

● Focusing attention “Are you feeling nauseous?” (recovery room) “Signal if you feel pain.” (recovery room)

● Ineffective negation and trivialization “You don’t need to worry.” “It’s just going to bleed a bit.”” (7)

But How Would Placebo Effect ME?

Another idea that occurred to me is that a Placebo Effect may play out in quite a strange way in ME. My initial reaction to Bottle 2 was mainly positive in a cognitive/emotional way. I felt much more optimistic, like I could do more and concentrate longer. Physically I seemed to get worse and had much worse insomnia.

What if a degree of pessimism is actually quite protective in ME? I used to be prone to a boom and bust cycle but usually now level it out with Pacing. In my burst of optimism, sensible Pacing evaporated and I did more because I believed I was taking something beneficial (although I also knew you’re meant to carry on Pacing!). The extent of my reaction was out of my normal spectrum, but if I get mentally over stimulated I do often have trouble sleeping. Doing too much without sleep will very quickly create a ME flare or relapse. A detail that supports this theory is my symptoms took a few days to go after stopping the experiment, knowing it had been a placebo. Fortunately I didn’t have a relapse.

Conclusion

My favourite explanation at the moment is it was actually a placebo effect (not nocebo) and I did too much activity wise as a result of feeling unrealistically positive (the extra symptoms were ME flare up).

Despite sometimes being unpleasant this experience and research has been helpful to me overall.

What will I take from this?

In terms of the specific therapeutic effects:

  • Mitoq seems to give me a small benefit in terms of energy, mental clarity and sleep but in my current circumstances this isn’t substantial enough to justify the cost

  • Starting Ivabradine was also unexpectedly studied and this seems to help me a bit in terms of more energy, better sleep, feeling more positive. It has also been really good for my heart rate and I can now consistently walk around my house (a very useful and noticeable improvement).

In terms of firsthand experience of taking a placebo tablet and reading more about this:

  • Placebo effects are powerful and useful to harness rather than being embarrassing

  • Optimism created by placebo effects feels better than caution or pessimism

  • BUT optimism can be a threat to careful Pacing, so routine needs to be maintained (or only slowly adjusted) no matter how much I believe I can suddenly do more

  • ‘Side effects’ can sometimes be Nocebo Effects but this can be counteracted by being vigilant about messages from medical staff and my own negative suggestions.

Have you ever taken a placebo tablet?

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References
1) Nijs J, Nees A, Paul L, De Kooning M, Ickmans K, Meeus M, Van Oosterwijck J (2014). Altered immune response to exercise in patients with chronic fatigue syndrome/myalgic encephalomyelitis: a systematic literature review. Exerc Immunol Rev. 2014; 20:94-116.
2) Cordero MD, Cano-García FJ, Alcocer-Gómez E, De Miguel M, Sánchez-Alcázar JA (2012). Oxidative stress correlates with headache symptoms in fibromyalgia: coenzyme Q10effect on clinical improvement. PLoS One. 2012;7(4)
3) Wyman M, Leonard M, Morledge T (July 2010). “Coenzyme Q10: a therapy for hypertension and statin-induced myalgia?”. Cleve Clin J Med 77​(7): 435–42.
4) Smith RA, Murphy MP (2010). Animal and human studies with the mitochondria-targeted antioxidant MitoQ. Ann N Y Acad Sci. 2010 Jul; 1201:96-103.
5) Price DD, Finniss DG, Benedetti F (2008) A comprehensive review of the placebo effect: recent advances and current thought. Annu Rev Psychol. 2008;59:565-90. http://www.ncbi.nlm.nih.gov/pubmed/17550344.
Further Reading
Placebo Effect from Cancer.org

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Footnotes

My Quantitative Results:

My score based results.

 I’ve added in some extra scores I kept. For example, I also provided a baseline of just Ivabradine and not Bottle 1 or 2, in order to see what difference starting new medication had made. In terms of getting a sense of these results my initial thoughts are:
  • pain – increases slightly with Mitoq but increases again with placebo tablet (suggests some expectation effect in both?)
  • energy – very slightly more on Mitoq but much less with placebo, so slight increase with Mitoq could be a real effect
  • clarity – changeable, seems to be effected by something other than this experiment
  • sleep – mitoq improved
  • depression – changeable, placebo improved
  • gastro symptoms – quite bad across conditions
  • general wellbeing – reduced by placebo/nocebo
  • activity – increased on mitoq, reduced on placebo tablet, so slight increase with Mitoq could be a real effect
  • digits test – general plateau
  • polygons test – had one brilliant week on Mitoq in top 5% of population, could be due to something else
  • grammatical/verbal test – hard to interpret

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