Benefits
Fewer errors on a rapid attention task in healthy older adults
In a 28-day placebo-controlled trial in 155 adults aged 50 to 70, 950 mg a day led to fewer false alarms than placebo on a rapid visual information processing task at the first test session after that day's dose on day 28, not before dosing or on day 1. Other memory and attention tasks did not differ from placebo, nothing was corrected for the many outcomes, and the maker sponsored the trial.
Lower state anxiety after 28 days in healthy older adults
In the same trial, self-rated state anxiety fell more over 28 days at 950 mg a day than with placebo or a ginkgo comparison, by about 3 points. The 475 mg dose and the mood rating scales did not differ from placebo. The registry entry, filed after the trial ended, lists cognition as the primary outcome (one attention-error difference among many tasks) and mood as secondary.
Prefrontal brain blood flow during demanding mental tasks
In a subset of 57 participants, near-infrared spectroscopy showed higher oxygenated hemoglobin and oxygen saturation in the prefrontal cortex during demanding tasks on day 1 with both doses compared with placebo. No such difference was seen after 28 days of use. This is a physiological marker of blood flow, not a measure of thinking performance.
Water maze learning in mice given Sideritis extracts (animal study)
In amyloid-model mice, a Finzelberg Sideritis scardica extract alone did not improve water maze performance, while a Sideritis euboea extract at the higher dose and a 1:1 blend did; aged mice got only the blend, which also helped. All lowered brain amyloid. Doses were 1.2 to 12 g per kg of body weight, two authors worked for the maker, and these are animal findings only.
EEG patterns in rats given the extract (animal study)
In freely moving rats, 50 mg per kg of a Finzelberg 20% ethanol Sideritis scardica extract shifted brain wave patterns in a way the authors likened to ginkgo extract, and in brain slices it raised nerve cell responses to stimulation. Movement did not differ from control. These EEG signals are markers, not measures of thinking or mood, and a maker employee initiated the study.
Mechanism of action
Monoamine reuptake inhibition in laboratory tests
In rat brain preparations, Sideritis scardica extracts slowed the reuptake of serotonin, noradrenaline and dopamine, and a methanol extract strongly inhibited the human serotonin transporter in cells. An ethanol extract also made the antidepressant fluvoxamine act at lower concentrations. The abstract does not name the extract maker, and this has not been measured in people.
Proposed blood vessel effects of phenolic acids
The trial authors suggest that phenolic acids in the extract may widen blood vessels through nitric oxide, which could explain the day 1 rise in prefrontal oxygenation. Nitric oxide and blood vessel function were not measured in the trial, so this remains a hypothesis.
Amyloid handling in worm and mouse models
In worms engineered to make human amyloid beta, extracts made from Sideritis scardica herb supplied by Finzelberg reduced amyloid clumps by up to 21% and delayed paralysis, with 40% and 50% ethanol extracts most active. In mice, Finzelberg extracts lowered brain amyloid with more microglial clearance and higher ADAM10. These are model findings, not evidence in people.
Clinical trials
Randomized, double-blind, placebo-controlled parallel-groups trial of a 20% ethanol Sideritis scardica extract at 475 or 950 mg a day for 28 days, with 240 mg ginkgo as an active control; the maker and its distributor cite this trial for Concental. Sponsored by Finzelberg (Martin Bauer Group); three of nine authors were Finzelberg employees and one was an independent consultant. Registered after completion as NCT03475823. (Wightman et al. 2018, Nutrients)
155 healthy men and women aged 50 to 70 were randomized; cognition was analyzed in 140, state anxiety in 142, blood pressure in 133 and prefrontal blood flow in 57.
Versus placebo, 950 mg gave fewer false alarms on the rapid visual information processing task at the first session after that day's dose on day 28, with no difference before dosing that day (p = 0.017) and a larger fall in state anxiety over 28 days (p = 0.022). Picture recognition and speed of attention differed only from ginkgo. Mood scales and blood pressure did not differ, and 475 mg showed no cognitive or anxiety difference from placebo. Both doses raised prefrontal oxygenation on day 1, not day 28. Many cognitive outcomes were tested with no correction across them. The registry, filed after completion, lists cognition as the primary outcome and mood as secondary.
Animal toxicity study (single oral dose up to 2000 mg/kg, and 250, 500 or 1000 mg/kg a day for 28 days with a 14-day recovery group) plus bacterial mutagenicity tests of a 20% ethanol extract of herb supplied by Finzelberg (drug to extract ratio 5 to 9:1, 30% maltodextrin); the first author was a Finzelberg employee and no external funding was stated. (Feistel et al. 2018, Toxins (Basel))
Sprague Dawley rats and Salmonella test strains (an animal and laboratory study).
No deaths, signs of toxicity or gross pathology after 2000 mg/kg. Over 28 days there were no changes in body or organ weight or food intake, and a few blood changes (white cell count in males at 500 mg/kg, calcium and sodium) were judged marginal and within normal limits; the no-observed-adverse-effect level was 1000 mg/kg a day. Ames tests of water, 20% and 50% ethanol and heptane extracts were negative. Animal data do not establish human safety.
Controlled animal study of daily gavage with Finzelberg 20% ethanol extracts of Sideritis scardica, Sideritis euboea or a 1:1 combination, at 1.2 or 12 g/kg in amyloid-model mice and 6 g/kg of the combination in aged mice; two authors were from Finzelberg, and the senior author's work was funded by public research grants. (Hofrichter et al. 2016, J Alzheimers Dis)
APP-transgenic mice (5 to 10 per group) and aged non-transgenic C57Bl/6 mice (an animal study).
In amyloid-model mice, Sideritis scardica extract alone did not shorten water maze escape times at either dose, while Sideritis euboea at the higher dose and the 1:1 combination did; aged mice received only the combination, which also shortened escape times. All extracts lowered buffer-soluble amyloid beta 42 by about 40 to 60% and reduced cortical neuron loss. Doses far exceed the human trial dose.
Animal study recording field potentials from four brain regions in freely moving rats after oral Sideritis scardica (50 mg/kg) or Sideritis euboea extract, plus hippocampal slice recordings; extracts made by Finzelberg with 20% ethanol (drug to extract ratio 6:1); a Finzelberg coworker initiated the study; not indexed in PubMed. (Dimpfel et al. 2016, J Behav Brain Sci)
Freely moving rats (7 given Sideritis scardica) and hippocampal slices from 25 rats (an animal and laboratory study).
Sideritis scardica lowered spectral power in a pattern the authors likened to ginkgo extract, while Sideritis euboea had the opposite effect. In slices, Sideritis scardica raised population spike amplitude at 12.5 to 100 mg/L. Movement did not differ from vehicle. EEG and slice signals are markers, not measures of how animals or people think or feel.