Self-Blinded L-Theanine RCT

post by niplav · 2023-10-31T15:24:57.717Z · LW · GW · 11 comments

Contents

  Experiment B: Self-Blinded RCT
None
11 comments

Value tracked	Effect size d (λ, p, σ change)	Effect size d (λ, p, σ change)
	200 mg Caffeine (n=1, m=50)	500 mg L-theanine (n=1, m=50)
Log-score substance prediction[1]	-0.6	-0.7
Absorption	0.61 (λ=13.3, p=0.00017, -0.072)	0.04 (λ=1.38, p=0.77, -0.07)
Mindfulness	0.58 (λ=11.8, p=0.0007, 0.021)	0.12 (λ=0.72, p=0.89, -0.018)
Productivity	0.58 (λ=28.9, p=1.3-12, 0.11)	-0.28 (λ=5.51, p=0.109, 0.03)
Creativity	0.45 (λ=51, p=4.6-27, 0.09)	-0.12 (λ=5.05, p=0.14, -0.04)
Happiness	0.27 (λ=10.6, p=0.002, 0.3)	0.16 (λ=3.98, p=0.27, -0.155)
Contentment	0.13 (λ=7.66, p=0.02, 0.47)	0.25 (λ=6.83, p=0.04, -0.04)
Relaxation	-0.11 (λ=5, p=0.15, 0.42)	0.12 (λ=1.5, p=0.74, 0.02)
Chastity[2]	-0.14 (λ=1.9, p=0.64, 0.11)	-0.03 (λ=1.15, p=0.8, 0.25)
Flashcard ease	0.003 (λ≈∞, p≈0, -0.009)	-0.072 (λ=∞, p≈0, -0.01)
Flashcard ease factor	-0.039 (λ≈∞, p≈0, -32.7)	0.0026 (λ=∞, p≈0, -18.9)
Flashcard new interval	0.011 (λ≈∞, p≈0, -1.88)	-0.016 (λ=∞, p≈0, 3.1)
Time per flashcard[3]	0.006 (λ≈∞, p≈0, 273.4)	0.003 (λ=∞, p≈0, 13.66)

L-Theanine is synergistic with caffeine in regards to attention switching^[318] and alertness^[319][320] and reduces susceptibility to distractions (focus).^[320][321] However, alertness seems to be relatively subjective and may not be a reliable increase between these two compounds,^[318] and increases in mood are either present or absent.^{[322][318][323]} This may be due to theanine being a relatively subpar nootropic in and of itself pertaining to the above parameters, but augmenting caffeine's effects; some studies do note that theanine does not affect the above parameters in and of itself.^[324] Due to this, any insensitivity or habituation to caffeine would reduce the effects of the combination as L-theanine may work through caffeine.

L-Theanine does not appear to be synergistic with caffeine in regards to attention to a prolonged and monotonous task.^[325]

—Kamal Patel, “Caffeine”, 2023

See also Examine, Wikipedia and Gwern.

Sitiprapaporn et al. 2018 test the effect of an unspecified quantity of L-theanine via Oolong tea on meditation on 10 university students (non-randomized, it seems). Data collected via EEG and indicates statistically significantly more alpha waves during meditation (although it is unclear how long the meditation was).

This paper is bad. The english is so horrendous it feels like I'm having a stroke while I'm reading it, but that would be fine if they were good at reporting methods, which they are not (missing amounts of L-theanine and duration of meditation, they also mention reading earlier in the article, which I assumed was the control activity, but it doesn't come up again?). Also they report differences between scores, not effect sizes, and some figures are screenshotted images from a Windows Vista clustering application.

Examine agrees on the cognitive effects of l-theanine (if not on meditation specifically):

L-Theanine supplementation in the standard dosages (50-250mg) has been repeatedly noted to increase α-waves in otherwise healthy persons. This may only occur in persons with somewhat higher baseline anxiety^[25][26] or under periods of stress (positive^[14] and negative^[27] results), but has been noted to occur during closed eye rest^[5] as well as during visuospatial tasks^[16] around 30-45 minutes after ingestion.^[5][4] It appears that only the α-1 wave (8-10Hz) is affected, with no influence on α-2 wave (11-13Hz).^[4]

Bill Willis, “Theanine”, 2022

Although I'm confused about the increased α-waves in "otherwise healthy patients"‽

Additionally, it notes that memory was slightly increased:

One study using a supplement called LGNC-07 (360mg of green tea extract and 60mg theanine; thrice daily dosing for 16 weeks) in persons with mild cognitive impairment based on MMSE scores, supplementation was associated with improved delayed recognition and immediate recall scores with no effect on verbal and visuospatial memory (Rey-Kim test).^[17]

Bill Willis, “Theanine”, 2022

Experiment B: Self-Blinded RCT

This time I explicitely divided my meditation into a concentration part (first 15 minutes) and a mindfulness part (last 30 minutes).

• Time for preparation: 93 minutes
• Cost of l-theanine pills:
  • Cost of l-theanine pills: $\frac{0.25€}{\text{500mg L-theanine pill}}\cdot 25\text{500mg L-theanine pills}=6.25€$
  • Cost of empty capsules: $0.75€$

Notes during consumption:

• 1st dose: Made a mistake while filling the envelopes, accidentally deblinded myself.
• 19th dose: Took L-Theanine & did my routine, then took a nap and woke up 3 hours later.
• 43rd dose: Woke up with "brain fog", meditation was dull & all over the place. Maybe because I'd been drying laundry in my room during the night? Also took nicotine later the day to kickstart some work on a project that needed to be finished.

Ran the experiment from 2023-06-22 to 2023-09-28, sometimes with pauses between samples.

I use the same statistical techniques as in the caffeine experiment, and start, as usual, with my predictions about the content of the pill:

>>> substances=pd.read_csv('../../data/substances.csv')
>>> experiment='B'
>>> substance='l-theanine'
>>> placebo='sugar'
>>> expa=substances.loc[substances['experiment']==experiment].copy()
>>> expa['datetime']=pd.to_datetime(expa['datetime'], utc=True)
>>> probs=np.array(expa['prediction'])
>>> substances=np.array(expa['substance'])
>>> outcomes=np.array([0 if i=='sugar' else 1 for i in substances])
>>> np.mean(list(map(lambda x: math.log(x[0]) if x[1]==1 else math.log(1-x[0]), zip(probs, outcomes))))
-0.705282842369643

This is not great. In fact, it's slightly worse than chance (which would be about -0.693). Not a great sign for L-theanine, and, in fact, it gets worse. I use the generalized and compacted code from the last experiments to get the other results, and they don't point a rosy picture for L-theanine:

>>> analyze('B', 'l-theanine', 'sugar')
absorption  mindfulness  productivity  creativity     happy   content   relaxed     horny      ease     factor       ivl       time
d     0.040887     0.124170     -0.278448   -0.116001  0.164261  0.254040  0.119069 -0.031665 -0.072098   0.002561 -0.015955   0.003073
λ     1.378294     0.720780      5.517769    5.049838  3.983760  6.833004  1.496601  1.148131       inf        inf       inf        inf
p     0.765758     0.894798      0.109735    0.146420  0.266491  0.045270  0.740705  0.813279  0.000000   0.000000  0.000000   0.000000
dσ   -0.067847    -0.017736      0.039855   -0.043241 -0.155797 -0.046668  0.019655  0.251454 -0.016542 -18.901846  3.108518  13.660820

It worsens productivity and creativity (though not quite statistically significantly, but it's on the way there), but at least it improves my mood somewhat (though those results, besides contentment, might as well be due to random chance). No clear effect sizes with the flashcards either.

So a hard pass on L-theanine, I think. Maybe it's better when combined with caffeine?

---

1. Higher is better. ↩︎

2. Whether higher or lower values are better here is not clear. ↩︎

3. The value of higher or lower values here is not clear: Do we want to spend more time per flashcard, or are we content with fast but sloppy performance? ↩︎

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