Natural, effective and safe treatment of flu with palmitoylethanolamide

Flu epidemics are the cause, each year, for 3-5 million people suffering from severe symptoms, and 250.000 to 500.000 people die due to the flu. Here you can read what happens when a flu virus enters the body. A natural compound reducing the flu severity and preventing it from happening therefore is quite important! Because the old ways of treatment are not adequate or sufficient.

1. Flu vaccinations are under debate due to their suboptimal balance between efficacy and safety
2. Flu vaccinations can only be useful, if taken before the flu season
3. Anti-flu drugs such as zanamivir en oseltamivir (Tamiflu) have come under pressure, due to again a suboptimal balance between efficacy and safety; quick resistance against these drugs by flu virusses have been reported.
4. Common anti-fever drugs such as aspirine and paracetamol are not helping, but making things worse

So their is a great need for a safe compound, which can be taken both to protect as well as to treat flu if needed. Such a compound is available. But many people are not aware of it, because it is not pushed by the pharmaceutical companies, it is a supplement and a natural body-own molecule. But it has been evaluated and found to be safe and effective in a number of double blind, placebo controlled trials!

Do not suppress normal fever in flu

New scientific findings suggest that suppressing fever can result in the infection of tens of thousands of additional people each flu season. So taking a simple aspirine is not a very good idea.

Fever-reducing meds may thus help spread the flu, so better to look for alternatives! One of the scietists of the McMaster University said:

Bolker said: “Parents and health care professionals alike have focused on making their children or patients feel better by reducing fever, without being aware of potentially harmful side effects at the population level.

Furthermore, Fever can lower the amount of virus in a sick person’s body and help immune responses work better.

We quote:

Reducing fever with drugs, instead of accompanying it in a physiological way, does limit the defensive action triggered internally by our body, giving the virus a chance to continue its diffusion and transmission to other living beings. In practice, lowering temperature during the flu season by using a chemical approach means facilitating the epidemic progression.

Now, with the availability of the natural immune-supportive supplement palmitoylethanlolamide, en new and natural treatment modus has become within reach. This is exactly the inroad from the plea above: to accompanying fever in a physiological way.

Breakthrough of a safe treatment principle in flu

Palmitoylethanolamide, or N-2-hydroxyethyl-palmitamide was introduced as Impulsin for the treatment of flu and respiratory infections by the company Spofa in the late 60s of last century, for the Czech market. The company went broke, and people forgot about the compound. However, since the work of the Nobel laureate professor Levi-Montalcini scientists started to re-discover this old compound. Very recently it German researchers found that the compound could be useful in treating difficult infections. (Redlich, 2014) Now PEA can be considered as a breakthrough natural therapy for flu and common colds.

PEA was already quite known at that time as a naturally occurring lipid compound and s potent inducer of non-specific resistance. The authors for instance referred to preclinical studies describing an increased survival rate amongst mice treated with palmitoylethanolamide and injected with different bacterial toxins or exposed to living bacteria (Raskova et al, 1972). This protective effect was quite impressive, see graph:

Protective effect of PEA

Protective effect of PEA

Furthermore, as they pointed out, PEA markedly increased the resistance of cellular and subcellular membranes to various noxious agents. (Obermajerovfi, 1973)

Three clinical studies with PEA in children

In 1969 the results of a first clinical prophylactic trial with PEA were reported. Treatment with Impulsin in children’s institutions showed a reduced incidence of respiratory infections in  those children. (Perlik, 1969) In 1977 a second trial in 457 children was reported (Plesnik, 1977). One year later, the results of a second trial in 4 year old children was reported, were a high dose of PEA was used, 30 mg PEA/ kg BW, without any safety concerns. (Widermannova, 1978)

The 1974 report of the prophylactic effect of PEA in two large double blind studies

Masek and colleagues reported in 1974 the results of two large scale double blind field trials done to evaluate the prophylactic efficacy of Impulsin in upper respiratory tract infections.

As the flu becomes more and more of an issue, and current prophylactic treatments are far from optimal, with minimal efficacy and many side effects issues, the natural molecule PEA needs more attention in the scientific community.

Based on the two prophylactic trials reported in 1974 (and based on a number similar trials) PEA should be considered as a useful, effective and safe prophylactic agent for respiratory infections.

Result of two pivotal trials published in 1974 on the effects and safety of PEA in respiratory infections

The studies were conducted in December 1972 in volunteers in two separate communities.

The studies were completed in February, 1973, and results were available of 1345 people. Forty one volunteers failed to complete the trial, either because they failed to take their tablets regularly, or they were lost to follow-up.

Volunteers were allocated to PEA or placebo treatment in a double-blind randomized manner and the code was not broken until the data had been prepared for statistical analysis. Each subject recieved a coded bottle containing 72 tablets. Volunteers in teh active arm of the study recieved bottles contained Impulsin, 300 mg/tablets, and the others recieved placebo tablets. The tablets were indistinguishable in appearance and taste.  Dose was 2 tablets of 300 mg three times daily for the first 12 days (1800 mg PEA/day).  Evaluations took place at weeks 6 or 8 after start treatment. 

In the first study employees of the Skoda Car Co. were entered in the study. Outcome variables recorded were: temperature of 37.5°C  or higher, headache, sore throat, myalgia, nasal  stuffiness or discharge, productive or dry cough,  malaise and fatigue. Subjects were instructed also to record each day whether they were sick or healthy.

Results:  Of the 444 subjects in the first trial available for analysis,  221 had taken the placebo (85 males and 136 females)  and 223 had had Impulsin (98 males and 125 females). Statistical analysis of the records of symptoms of  respiratory tract disease revealed that PEA treatment had markedly reduced the numbers of episodes of fever, headache and sore throat.  Episodes of fever and pain were significantly (p< 0.05) reduced in volunteers who received PEA by 45.5%

PEA reduces symptoms of flu

PEA reduces symptoms of flu

The total numbers of days of illness, was significantly reduced in the PEA group.

In the second trial 918 volunteers from an army unit entered; all volunteers were 18-20 years old, and all were men. In this study, volunteers received during the first 12 days treatment with 1800 mg PEA/day or placebo,
followed, by administration of one 300 mg tablet of PEA or placebo daily for the entire period of the trial. The results showed the same positive effect of PEA, which we here document as a graph and a table:

PEA in FLU-2png

In the graph we see the cumulative percentage of total disability due to acute respiratory infections in the second trial
which was significantly diminished by PEA. The results were more clear compared to the first trial, because in the soldier population the incidence of respiratory symptoms was much higher, probably due to a higher degree of contamination in a population living together in a very dense way.

The following table illustrates the significant difference between endpoints:

Significant less sickness experience in the PEA treated soldiers

Significant less sickness experience in the PEA treated soldiers

The incidence of disease amongst subjects who received PEA was 40% lower in the 6 week study and 32% lower in the 8 week period; the reductions were highly significant (p<0.0005).

These 2 trials both supported the value of PEA in the prophylaxis of respiratory infections and flu like symptoms. In later flu trials serology was taken to be certain of the existence of flu, these trials confirmed the results discussed here.

By the end of 1979 the results of three more trials in serological proven flu appeared (Kahlich, 1979).

In total 3 studies in children and 5 studies in adults have been conducted and reported in the literature. All these studies supported the safety of PEA up to doses of 30 mg/ kg BW, also in children, as well as the efficacy of PEA as a prophylactic and as a treatment intervention for flu and respiratory infections. In total more than 2000 people have been entered in these trials.

We end citing a recent conclusion drawn by Dutch scientists, who reviewed all PEA-flu data (Keppel Hesselink, 2013):

Given the results of 6 clinical trials in flu and the common cold, seen in the context of the serious criticism on the efficacy and safety of oseltamivir and zanamivir, PEA should be reconsidered by clinicians as a new treatment modality for the flu and respiratory infections due to its documented efficacy and more importantly its very benign side effect profile. Furthermore, oseltamivir and zanamivir are known to induce resistance; PEA has a very low likelihood of inducing resistance due to its mechanism of action. Finally, the ease of application of PEA offers the possibility to have a quick therapeutic answer ready in case of a flu epidemic, especially in cases of a mismatch between circulating strains and the recommendations from WHO.


Perlik, F., Ells, J., Raskovfi, H., Duben, J., Grublova, M., Kubcovfi, M., Neubauer, M., Rudolfova, S., Svandovfi, E., et al. A controlled clinical trial with “PEA” in children institutions. (in Czech) Cs. Fysiol. 18, 345–346 (1969)

Plesník V, Havrlantová M, Jancová J, Januska J, Macková O.[Impulsin in the prevention of acute respiratory diseases in school children].Cesk Pediatr. 1977 Jun;32(6):365-9.

Raskova, H., Masek, K., Linet, O. Non-specific resistance induced by palmitoylethanolamide. Toxicon 10, 485–490 (1972)

Obermajerovfi, H., Masek, K., Seifert, J., Buchar, E., Havlik,I. Structural and functional changes in liver mitochondria of mice fed palmitoylethanolamide (PEA). Biochem. Pharmacol. 22, 2529–2536 (1973)

K. Masek, F. Perllk, J. Klima, R. Kahlich. Prophylactic Efficacy of N-2-Hydroxyethyl palmitamide (Impulsin®) in Acute Respiratory Tract Infections. Europ. J. Clin. Pharmacol. 7, 415-419 (1974)

Widermannova, D, Widermann, D, Lokaj, J. Prophylaxtic administration of Impulsin to healthy children. Cas Lec Ces 1978, 117: 1030-1034

Perlík F, Rasková H, Elis J. Anti-inflammatory properties of N(2-hydroxyethyl) palmitamide. Acta Physiol Acad Sci Hung. 1971;39(4):395-400.

Perlík F, Krejcí J, Elis J, Pekárek J, Svejcar J. The effect of N-(2-hydroxyethyl)-palmitamide on delayed hypersensitivity in guinea-pig. Experientia. 1973 May 1;29(1):67-8.

Kahlich R, Klíma J, Cihla F, Franková V, Masek K, Rosický M, Matousek F, Bruthans J.Studies on prophylactic efficacy of N-2-hydroxyethyl palmitamide (Impulsin) in acute respiratory infections. Serologically controlled field trials. J Hyg Epidemiol Microbiol Immunol. 1979;23(1):11-24.

D. J. D. Earn, P. W. Andrews, B. M. Bolker. Population-level effects of suppressing fever. Proceedings of the Royal Society B: Biological Sciences, 2014; 281 (1778): 20132570 DOI: 10.1098/rspb.2013.2570

Redlich S, Ribes S, Schütze S, Nau R. Palmitoylethanolamide stimulates phagocytosis of Escherichia coli K1 by macrophages and increases the resistance of mice against infections. J Neuroinflammation. 2014 Jun 14;11(1):108.

J. M. Keppel Hesselink, Tineke de Boer, and Renger F. Witkamp, “Palmitoylethanolamide: A Natural Body-Own Anti-Inflammatory Agent, Effective and Safe against Influenza and Common Cold,” International Journal of Inflammation, vol. 2013, Article ID 151028, 8 pages, 2013. doi:10.1155/2013/151028

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