Dopamine Supplement Doesn't Work

I mentioned about being able to walk further when in a new environment or routine. I figured it could be a dopamine effect, so I tried a dopamine supplement to see if I could get the effect without changing my environment. Well, it didn't work. I tried it for a month and there hasn't been any improvement. Here is the graph:

August 21 is the date I started taking 2 dopa pills. As you can see, the 7 day rolling sum of the number of steps taken actually decreased.  Part of it got to do with getting sick after experimenting with squats, etc. But you'd expect the CFS threshold is raised with dopamine and therefore I should get sicker less often. Apparently it didn't. This, of course, is only a month worth of data with one patient, so I can't draw any conclusion. But it certainly doesn't give me any reason to experiment further with it.

The dopamine supplement, by the way, was DOPA Mucuna from Amazon.

This doesn't necessarily invalidate the dopamine theory. It only means that the dopaminergic supplement didn't work for me. Motivation and excitement may still work. My next plan? Stay tuned.

Out of Jail After 3 Days

It's good to be "healthy" again. I just got of the jail of post-exertional sickness of 3 days after adding 2 squats to my daily routine. In the nick of time too; my refrig was totally empty. I went out for errands on Muni and restocked it.

When you are constantly sick, you don't really know how sick you are; post-exertional sickness is just worsening of your symptoms. When you improve enough though, you realize the post-exertional sickness is really flu-like: it has clearer onset and recovery. And you know how fresh and free it feels when you recover from a flu after being sick for a few days.

Measuring Fatigue with HRV Doesn't Seem to Work

In the paper "Frontier Study of Fatigue.." the Japanese researchers claim that measuring HRV is a reliable way to measure fatigue. They compared HF/LF measure to patients' subjective fatigue as determined by Chalder Scale and SF-36 survey. Also, over at healthrising.com, one of the members posted her experience with HRV and showed the correlation to her post-exertional sickness.

Since I got Polar H7, I decided to give it a try. I downloaded Elite HRV, a free android app, and measured morning readiness when I wake up. I also measured HRV at various times throughout the day. Below is the data over a period of one month:

                  Date hrv balance fatigue morning afternoon evening
1   8/10/2016 11:57:00  49      NA      NA      NA        NA      NA
2   8/10/2016 14:37:00  45      NA      NA      NA        NA      NA
3   8/10/2016 20:06:00  51      NA      NA      NA        NA      NA
4    8/11/2016 8:44:00  48       6      NA     4.9       5.1     5.0
5    8/11/2016 8:44:00  49      NA      NA      NA        NA      NA
6   8/11/2016 12:00:00  42      NA      NA      NA        NA      NA
7   8/11/2016 16:27:00  58      NA      NA      NA        NA      NA
8   8/11/2016 20:09:00  47      NA      NA      NA        NA      NA
9    8/12/2016 8:15:00  63       7      NA     5.1       5.0     5.2
10   8/12/2016 9:32:00  55      NA      NA      NA        NA      NA
11   8/12/2016 9:36:00  51      NA      NA      NA        NA      NA
12  8/12/2016 12:00:00  56      NA      NA      NA        NA      NA
13  8/12/2016 15:04:00  51      NA      NA      NA        NA      NA
14  8/12/2016 19:54:00  47      NA      NA      NA        NA      NA
15  8/12/2016 20:30:00  47      NA      NA      NA        NA      NA
16  8/12/2016 20:57:00  48      NA      NA      NA        NA      NA
17  8/12/2016 21:51:00  53      NA     5.2      NA        NA      NA
18  8/12/2016 21:53:00  52      NA     5.2      NA        NA      NA
19  8/12/2016 21:55:00  54      NA     5.1      NA        NA      NA
20  8/12/2016 22:14:00  54      NA     5.1      NA        NA      NA
21  8/12/2016 22:44:00  47      NA     5.1      NA        NA      NA
22   8/13/2016 8:43:00  51       9     5.1     5.2       5.0     5.4
23  8/13/2016 11:01:00  46      NA     5.2      NA        NA      NA
24  8/13/2016 11:32:00  53      NA     5.2      NA        NA      NA
25  8/13/2016 12:51:00  45      NA     5.1      NA        NA      NA
26  8/13/2016 13:20:00  44      NA     5.0      NA        NA      NA
27  8/13/2016 16:39:00  56      NA     5.0      NA        NA      NA
28  8/13/2016 17:19:00  53      NA     5.0      NA        NA      NA
29  8/13/2016 18:52:00  47      NA     5.2      NA        NA      NA
30  8/13/2016 20:33:00  43      NA     5.3      NA        NA      NA
31   8/14/2016 7:23:00  44       6     5.2     5.2       5.0     5.0
32  8/14/2016 10:19:00  52      NA     5.0      NA        NA      NA
33  8/14/2016 20:38:00  50      NA     5.0      NA        NA      NA
34  8/14/2016 22:53:00  46      NA     5.2      NA        NA      NA
35   8/15/2016 7:25:00  50       9     5.0     5.0       5.2     5.3
36  8/15/2016 14:38:00  39      NA     5.0      NA        NA      NA
37  8/15/2016 15:13:00  48      NA     5.2      NA        NA      NA
38   8/16/2016 9:03:00  48       8     5.3     5.3       5.2     5.2
39  8/16/2016 18:37:00  45      NA     5.2      NA        NA      NA
40   8/17/2016 9:38:00  48       8     5.1     5.0       5.0     5.0
41  8/17/2016 17:34:00  47      NA     5.0      NA        NA      NA
42   8/18/2016 8:33:00  58       7     5.1     5.2       5.2     5.1
43   8/18/2016 8:38:00  54      NA     5.1      NA        NA      NA
44  8/18/2016 10:33:00  48      NA     5.2      NA        NA      NA
45  8/18/2016 13:09:00  46      NA     5.0      NA        NA      NA
46  8/18/2016 17:14:00  51      NA     5.1      NA        NA      NA
47  8/18/2016 17:17:00  49      NA     5.1      NA        NA      NA
48  8/18/2016 12:09:00  53      NA     5.2      NA        NA      NA
49   8/19/2016 9:03:00  48       8     5.4     5.3       5.0     5.0
50   8/19/2016 9:08:00  44      NA     5.3      NA        NA      NA
51  8/19/2016 11:45:00  50      NA     5.0      NA        NA      NA
52  8/19/2016 14:02:00  41      NA     5.1      NA        NA      NA
53   8/20/2016 8:48:00  51       9     4.9     5.1       5.1     5.1
54   8/20/2016 8:52:00  55      NA     4.9      NA        NA      NA
55  8/20/2016 15:13:00  41      NA     5.1      NA        NA      NA
56  8/20/2016 17:05:00  56      NA     5.2      NA        NA      NA
57  8/20/2016 21:14:00  50      NA     5.0      NA        NA      NA
58   8/21/2016 9:39:00  49       8     5.2     5.3       4.9     5.1
59   8/21/2016 9:42:00  43      NA     5.3      NA        NA      NA
60  8/21/2016 14:17:00  46      NA     5.0      NA        NA      NA
61  8/21/2016 16:55:00  47      NA     4.9      NA        NA      NA
62  8/21/2016 18:08:00  47      NA     5.1      NA        NA      NA
63  8/21/2016 21:13:00  47      NA     5.2      NA        NA      NA
64   8/23/2016 7:51:00  46       7     5.2     5.3       5.1     5.3
65   8/24/2016 8:04:00  51      10     5.0     5.3       5.2     5.2
66   8/24/2016 8:10:00  51      NA     5.0      NA        NA      NA
67  8/24/2016 18:47:00  48      NA     5.1      NA        NA      NA
68   8/25/2016 7:42:00  48       8     5.2     5.3       5.2     5.0
69   8/26/2016 8:19:00  49       8     5.2     5.3       5.1     5.3
70   8/26/2016 8:22:00  47      NA     5.2      NA        NA      NA
71   8/26/2016 9:43:00  47      NA     5.2      NA        NA      NA
72  8/26/2016 12:25:00  51      NA     5.2      NA        NA      NA
73  8/26/2016 12:27:00  48      NA     5.2      NA        NA      NA
74  8/26/2016 12:29:00  47      NA     5.2      NA        NA      NA
75  8/26/2016 12:35:00  50      NA     5.2      NA        NA      NA
76  8/26/2016 12:52:00  47      NA     5.0      NA        NA      NA
77  8/26/2016 12:54:00  50      NA     5.0      NA        NA      NA
78  8/26/2016 16:05:00  32      NA     5.0      NA        NA      NA
79  8/26/2016 16:21:00  33      NA     5.1      NA        NA      NA
80  8/26/2016 16:36:00  31      NA     5.2      NA        NA      NA
81  8/26/2016 18:04:00  50      NA     5.1      NA        NA      NA
82   8/27/2016 8:24:00  45       6     5.1     5.3       5.4     5.1
83   8/27/2016 8:28:00  43      NA     5.1      NA        NA      NA
84   8/27/2016 8:29:00  38      NA     5.1      NA        NA      NA
85  8/27/2016 14:12:00  50      NA     5.0      NA        NA      NA
86   8/28/2016 9:57:00  41      NA     5.1      NA        NA      NA
87  8/28/2016 10:00:00  40       3     5.1     5.1       5.2     5.3
88   8/29/2016 9:14:00  50       8     5.1     5.1       5.0     5.3
89   8/29/2016 9:17:00  47      NA     5.1      NA        NA      NA
90   8/29/2016 9:19:00  46      NA     5.1      NA        NA      NA
91   8/30/2016 8:48:00  46      NA     5.1      NA        NA      NA
92   8/30/2016 8:49:00  46       8     5.1     5.0       4.9     5.1
93  8/31/2016 10:08:00  49       9     5.1     5.3       5.1     5.1
94  8/31/2016 10:11:00  47      NA     5.1      NA        NA      NA
95    9/1/2016 9:23:00  45      NA     5.1      NA        NA      NA
96    9/1/2016 9:25:00  43       6     5.1     5.1       4.9     4.8
97    9/2/2016 9:17:00  48      NA     5.2      NA        NA      NA
98    9/2/2016 9:19:00  42       6     5.2     4.9       5.0     5.0
99    9/3/2016 8:07:00  48      NA     4.9      NA        NA      NA
100   9/3/2016 8:11:00  44       8     4.9     5.3       5.1     5.0
101   9/4/2016 9:20:00  50      NA     5.1      NA        NA      NA
102   9/4/2016 9:24:00  42      NA     5.1      NA        NA      NA
103   9/4/2016 9:26:00  40       6     5.1     5.3       5.2     5.2

And here are the scatter plots between readiness/balance and fatigues throughout the day and the correlations:

And finally, the scatter plots between 1 minute snapshot hrv taken throughout the day and fatigue:

HRV is the high frequency variability measured by RMSDD of R-R distance of the heart beats. Balance is the balance between sympathetic and parasympathetic activities, and the higher the better it is. Elite HRV computes this values based on how far HRV is from the optimum value. Fatigue is my subjective fatigue rating.

As you can see from the scatter plots, there isn't much correlation between the ANS balance or HRV and fatigue. They range from -20% to +23%. (One could question my subjective fatigue rating, but I do have enough confidence in it since it correlates 81% to time spent lying down).

It's only a month worth of data, so I can't draw a definitive conclusions from it. But the HRV and balance are all over the map, I basically lost interest in pursuing it further. Maybe HF/LF measure, as done in the Frontier Study of Fatigue, will have a better correlation. But LF  measure is influenced by both sympathetic and parasympathetic nerve, and is therefore controversial. Even if it works, HRV method poses logistical problem as it requires the patients to lie down for over 5 minutes  and pace the breathing. It is not a viable measure of fatigue. Especially if it requires medical grade equipment as done in the Frontier Study.

For now, I'm moving on to the walking pace as the measure of fatigue. It has an advantage of not requiring any action on the patient's part and I think it'll correlate to overall fatigue better because fatigue will result in sluggishness and slower walking pace whether it is sympathetic, parasympathetic, mental or physical. Stay tuned.

Squats, Still a Killer Exercise

How is it possible that I can walk 2.5 miles (with 3 breaks) and yet two squats send me to the pound? I knew that squats can make me keel over. But I decided to experiment again since I have the improvement under the belt. No luck. I threw in two squats to the daily regimen and I got sick for 3 days.

Enough with the experiment. I now know that there is no discernable improvement in the walking speed or squat. I'll try again when I can walk 5 miles. (Yes, the walking speed increases arithmetically as the distance increases exponentially).

CFS as Hibernation

Spent 3 days in a bad mood. Apparently cleaning the bathroom the day after walking 2 mi and then walking 2 mi again the day after was too much. The cumulative effect of exertion is still alive and well; it is only less pronounced because my tolerance to exertion went up.  I'll have to go back to cleaning the bathroom in lieu of, not in addition to, the (bi-daily) walk.

Now, today's topic. The UCSD researchers announced this week that they discovered anomaly in the metabolomics of CFS patients. Out of 600 or so metabolites they tested, 80% were severely reduced compared to matched controls. From this, they speculated that CFS patients are in a hibernation state like Dauer worms. For some reason, the body is mistakenly putting the patients in a hypometabolic state that only allowed survival and no more, at a great expense to the quality of life.

One issue with this theory is that humans don't hibernate. Dauer worms and bears can slow down their metabolism, lower body temperature and burrow into a hole or cave. For humans, hibernation means death unless fed and taken care of by other humans. That not a viable evolutionary strategy generation after generation. So it can't possibly be an evolutionary adaptation. Perhaps it is an ancient cellular level response (they call it CDR, or cellular danger response) mistakenly activated. But that still does not explain slew of neurological CFS symptoms. Worse yet, you can't explain with the hibernation theory the ability to exert normally only to get sick the next day.  (If you are in a dauer state, you should not be able to exert at the first place). So, for now,  the metabolic anomaly is more likely than not yet another symptom of CFS rather than the cause of it.

The problem with CFS research that I see is that researchers focus on their specialties and then speculate whatever the anomaly they find as the cause of CFS. Thus, virus people blame EBV, psychiatrists blame depression, endocrinologists blame HPA axis, and geneticists blame genetic expressions. Now we can add to that growing list gut microbiome and metabolomics.  It's the proverbial blind men and the elephant. What we need is a creative thinking, as recently done in schizophrenia and alzheimer's, that can put together all these clues and zero in on the real cause, so that we can come up with a real solution. The problem is, with only $5 million dollars out of NIH's gazillion dollar budget allocated to CFS research, it's not going to attract a lot of researchers. Quantity usually leads to quality in research, and we need that quantity to solve this problem.

As far as I am concerned, CFS is still a neuromuscular disorder, mediated by the immune system.
I think the term Myalgic Encephalomyelitis will ultimately proven right, except that it is the inflammation sensitivity, not the inflammation itself. And the paper's finding that the metabolic response was the opposite to the response to infection or inflammation only proves that there is no infection or actual inflammation in CFS.