Special Studies: Unrefreshing Sleep

This is a common symptom for both ME/CFS and Long COVID. This is reported often in samples, and thus being examined if it reaches our threshold for inclusion as defined in A new specialized selection of suggestions links. It does, but the degree of association (z-scores) are lower than prior special studies despite having a larger study population.

Study Populations:

Sleep: Unrefreshed Sleep1041107
  • Bacteria Detected with z-score > 2.6: found 139 items, highest value was 5.1
  • Enzymes Detected with z-score > 2.6: found 208 items, highest value was 5.2
  • Compound Detected with z-score > 2.6: found 1 items, highest value was 2.8 – effectively zero when false detection rate is considered.

The highest z-scores above are less than other symptoms despite larger sample size. This indicates that the causes are more diverse and thus less homogeneous bacteria shifts.

Location of this custom filter

Interesting Significant Bacteria

All bacteria found significant had too low levels.

Low Veillonella is reported in some studies associated with sleep issues with it’s consumption of lactic acid(lactate) being cited as a possible factor:

BacteriaReference MeanStudyZ-Score
Veillonella (genus)406322825.1
Actinobacillus (genus)3531334.9
Bifidobacterium catenulatum subsp. kashiwanohense (subspecies)3211004.8
Clostridium cellulovorans (species)40174.8
Bifidobacterium kashiwanohense PV20-2 (strain)3181004.8
Actinobacillus porcinus (species)184734.6
Thiobacillus thiophilus (species)85264.6

Interesting Enzymes

All enzymes found significant had too low levels.

EnzymeReference MeanLong COVID MeanZ-Score
(1->4)-alpha-D-galacturonan lyase (
2-acetylphloroglucinol C-acetyltransferase (
phylloquinone:disulfide oxidoreductase (
[RNA] 5′-hydroxy-ribonucleotide-3′-[RNA fragment]-lyase (cyclicizing; [RNA fragment]-3′- nucleoside-2′,3′-cyclophosphate-forming and hydrolysing) (
CMP-N-acetyl-beta-neuraminate:beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-R (2->3)-N-acetyl-alpha-neuraminyltransferase (configuration-inverting) (
propane-1,3-diol:NAD+ 1-oxidoreductase (
ATP:(Kdo)-lipid IVA 3-deoxy-alpha-D-manno-oct-2-ulopyranose 4-phosphotransferase (

Bottom Line

The key take away is that lactate/lactic acid levels appears to be a significant contributor. The reason that it is high is the lack of lactate consumers. Removal of lactate producing probiotics from supplements appears to be a logical first step (i.e. Lactobacillus), followed by taking Vitamin B1 shortly before bed time.

For suggestions on lowering it, see this old post of mine in the ME/CFS context.

The issue may not be lactate by itself, but by the form of lactate (d-lactate –> bad)

Results and conclusion: Administration of L-lactate does not influence sleep-wake cycle of experimental animals. At the same time, its artificial optical analog D-lactate induces the significant (as compared to the control) decrease in wake (34.8% to 26.5%) and increase in slow wave sleep (57.4% to 69.2%). It has been suggested that D-lactate may be the antagonist of one or several L-lactate receptors.

[D-lactate as a novel somnogenic factor?] [2020]

“Thiamine (Vitamin B1) replenishment at intravenous doses of 100 mg every 12 h resolved lactic acidosis and improved the clinical condition in 3 patients.” [1997]

“Lactomin[300 mg Lactobacillus acidophilus, 300 mg Bifidobacterium longum] was discontinued, and she was treated with sodium bicarbonate and oral antibiotics. The probiotics the patient had taken were likely the cause of D-lactic acidosis ” [2010]

3 thoughts on “Special Studies: Unrefreshing Sleep

  1. So I have chronic Lyme , mold toxin illness bartonella celiac and sibo . I was doing well until covid this Jan 8 . Got better and after I started back to exercise I got long covid severe insomnia ( no sleep at all ) . I never had a problem with insomnia . Also palpitations. Chemical smells and tintinitus . Went on long haul covid frontline Dr protocol . Still having problems . I’m sending this to my doctor . Anything else I can tell her

    1. My usual advice, get a microbiome sample (Ombre or Biomesight are best), and use the filtering on the site to get suggestions and print those off to discuss with your MD.

      Since you have multiple conditions, do each of the special studies that applies and then look at the consensus report.

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