Palmitoylethanolamdide is hot. In mid 2013 already 36 publications related to this compound were indexed in the medical database PubMed. It is clear that its therapeutic value is starting to be realized by the medical community.
That is probably one of the reasons for bringing a new PEA formulation to the market.
In 2013 such a new PEA formulation was introduced by the Italian company under the name Glialia or PEALut. Glialia comes in packages of 20 sachets, each sachet containing 55% PEA, 38% sorbitol (a pharmaceutical sweetener) and 6% luteolin, a foodsupplement. PEALut is a marketed brandname too, already used in one preclinical study.
The indication according to package insert for Glialia is neuroinflammation, although clinical tests supporting this indication for this combination nutraceutical are missing.
The added supplement luteolin has not been evaluated in clinical trials so far, and related to the claimed neuro-inflammatory indication researchers suggested in a paper in the journal ‘Neurological research’ that lutolin is not of value in the neuro-inflammatory state of MS:
“Despite beneficial reports regarding non-herbal supplements such as alpha-lipoic acid, luteolin, evening primrose oil and vitamins such as B12, the lack of evidence does not support their prophylactic use.”
The product has been developed according to the latest insights of micronization techniques developed by the Italian company, and the result of this technique are particles we herewith compare to the pure PEA which is to be found in PeaPure capsules.
The % of PEA in Glialia sachets according to the table printed on the box of Glialia is 55%. PEA is an saturated fat. However each 100 % Glialia product contains only 47% saturated fat, according to the same table on the box. So most probably each sachet of Glialia contains even less than 55% PEA, only 47%.
The Glialia product is positioned as a new PEA product specifically for neuro-inflammation. However, the clinical relevance of the supplement added is unclear. Pharmaceutical compositions containing PEA without any herbal or supplement added seem to remain the most logical choice in treating patients suffering from chronic pain or chronic inflammation.
In the table below, the amount of PEA in all marketed formulations are depicted in the blue bars. In the red bars other compounds reside, such as excipients (magnesium stearate) and sweeteners (sorbitol), as well as other supplements (polidatin or luteolin).
Package insert of Glialia (PEALut)
The package insert of Glialia states:
“The central nervous system tissue, subject to recurrent and/or chronic neuroinflammatory conditions of different origin, tends to exhaust its own capacity to synthesize the endogenous Palmitoylethanolamide while, at the same time, increases the oxidative tone of the district, raising in this way the risk factor of neurodegeneration for several diseases- of degenerative, dismetabolic, traumatic origin- affecting the central nervous system.” (sic)
This part of the package insert most probably is based on the preclinical findings were palmitoylethanolamide could inhibit neuro-inflammation in models of Alzheimer, Parkinson’s disease, multiple sclerosis, stroke and neuro-trauma. However, in all these models, pure palmitoylethanolamide has been evaluated and found to be positive. None of these studies evaluated the value of the supplement luteolin as an adjunct to palmitoylethanolamide.
Although luteolin seems to have anti-inflammatory properties of its own, it also can aggravate certain inflammatory states, as has been pointed out by Karrasch et al (2007). Furthermore, the dose selected in Glialia (70 mg luteolin) is far below the effective dose tested in human according to Taliou(2013); they used a dose of 100 mg luteoline per 10 kg bodyweight. We could identfy only one study were the efficacy and safety of luteolin in man was described, a pilot trial in 50 children.
Side effects of luteolin
As a side effect irritability was noticed in more than half of all children in the first clinical trial reported in 2013. The authors stated:
The most frequent adverse effect was an increased irritability (27 of 50), of various durations, that led to study withdrawal in 6 participants.
Other observed side effects in this pilot trial of luteolin were abdominal pains, sleeping difficulties, facial tic, increased aggression and facial flushing.
In addition to these side effects, in vivo studies recently showed that luteolin significantly blunted the effect of insulin to reduce blood glucose, and the result suggested that luteolin induces glucose intolerance by attenuating insulin sensitivity (Lu Shao et al, 2013)
This new PEA formulation based on PEA combined with lutolin, branded as Glialia, seems therefore at the moment to lack scientific support, and the clinical rationale to add lutolin is lacking. Furthermore, its safety profile to date is unclear, as luteolin has not been tested yet in clinical trials in more than 50 people. Furthermore, the safety profile of luteolin is debatable, especially in diabetic patients.
Karrasch T, Kim JS, Jang BI, Jobin C. The flavonoid luteolin worsens chemical-induced colitis in NF-kappaB(EGFP) transgenic mice through blockade of NF-kappaB-dependent protective molecules. PLoS One. 2007 Jul 4;2(7):e596.
Taliou A, Zintzaras E, Lykouras L, Francis K. An open-label pilot study of a formulation containing the anti-inflammatory flavonoid luteolin and its effects on behavior in children with autism spectrum disorders. Clin Ther. 2013 May;35(5):592-602. doi: 10.1016/j.clinthera.2013.04.006.
Lu Shao et al. Opposite Effects of Quercetin, Luteolin, and Epigallocatechin Gallate on Insulin Sensitivity Under Normal and Inflammatory Conditions in Mice Inflammation, Vol. 36, No. 1, February 2013 ( # 2012) DOI: 10.1007/s10753-012-9514-x