Epitalon protocols in the published literature

What is the recommended protocol for taking Epitalon?

animal model

There is none, and that is a fact about the published record rather than a refusal to answer. No regulator has set an amount, and no study among the research behind this page compared different amounts of Epitalon in people to find one. What exists instead is a set of animal protocols, each written by investigators for one experiment.

The protocol that recurs most frequently comes from the St Petersburg group's lifespan and tumour experiments in mice. In the lifelong mouse study, female mice were subcutaneously injected on 5 consecutive days every month with 1.0 microg/mouse (approximately 30-40 microg/kg) of Epitalon, against saline in the control group.1

That is a study parameter for an animal weighing a few tens of grams. Reporting it is not the same act as recommending it, and the sections below set out the other published protocols so that the full range is visible.

What amounts did the mouse and rat studies use?

animal model

Almost every rodent experiment administered between a tenth of a microgram and one microgram per animal, injected beneath the skin. In mice genetically engineered to develop breast tumours, the peptide was given in a single dose of 1 microg/mouse for 5 consecutive days every month.2 In older mice observed for spontaneous tumours, Epitalon was injected at a dose of 0.1 microg, 5 times a week.3

Rats received comparable quantities. In a colon cancer experiment, rats were given Epitalon at a single dose of 1 microg during the whole experiment, five days a week.4 In the lighting experiments, female rats received Epithalon (0.1 microg daily 5 times a week from the age of 4 months).5

Notice that the investigators set the amount per animal, not per kilogram, in nearly every case. A rat weighs roughly ten times as much as a mouse, so the same microgram figure is a very different exposure in each species, which is one reason these numbers do not carry across from one animal to another.

What amounts were used in monkeys?

animal model

The monkey studies are the closest animal model to people, and they used a short course rather than a long one. Old and young female rhesus monkeys received epitalon (at the dose 10 micrograms/animal/day intramuscularly during 7-10 consecutive days).6

The same paper administered the extract, epithalamin, at the dose 5 mg/animal/day intramuscularly during 10 consecutive days, a quantity five hundred times larger by weight.6 That gap is expected, because the extract is a mix of many peptides and Epitalon is a single one. It also shows why an amount quoted for epithalamin must never be read as an amount of Epitalon.

The outcome measured was night-time melatonin, and the course was short and closely watched. A ten-day course of shots in a monkey does not tell anyone what a longer course would do, in a monkey or in a person.

What did the human studies give?

human RCT

For Epitalon itself, the abstracts we could find specify no quantity whatsoever. The retinal study and the melatonin study in middle-aged people both report results without stating how much was administered, by which route, or for what duration.

The human courses that are described all involved the extract. In the randomised coronary study, long-term treatment with epithalamin (6 courses over 3 years) was given in addition to standard medical care.7 In the 266-person study, the bioregulators were applied for the first 2-3 years of observation, with follow-up continuing for six to eight years.8

A separate group in that programme was treated with Thymalin combined with Epithalamin annually for 6 years.9 These descriptions indicate how frequently a course was repeated, not how much each course contained. They are also courses of a cattle-derived extract administered in a clinical setting, which is a different preparation from a vial of synthetic peptide.

How often can you take Epitalon peptide?

animal model

The experiments used two principal rhythms, and neither was ever tested against the other. One is a five-day block repeated monthly, as in the mouse lifespan and breast tumour experiments. The other is five injections weekly, continuing for months, as in the rat colon and lighting experiments.

A third pattern appears in a memory experiment, where Epitalon administered in a daily dose of 0.1 microg per animal beginning with the age of 4 months was continued as the rats aged over two years.10 Senescence-accelerated mice, a strain bred to age quickly, received s.c. injections of epitalon at a single dose 1mkg/mouse five times weekly in monthly cycles, where mkg is a Russian abbreviation for microgram.11

So the honest answer is that frequency varied between experiments and was not itself the subject of any investigation we could find. Monthly blocks and weekly schedules were chosen by the investigators, rather than derived from measurements of how long the peptide persists in the body, which none of these sources reports.

How long should you take Epithalon?

animal model

None of the studies we could find specifies a duration for a person, and course lengths in animals ranged from approximately a week to an entire lifetime. At the shorter extreme, the monkey courses lasted between seven and ten days. At the longer extreme, several mouse experiments administered the peptide from early adulthood until natural death.

In one breast tumour experiment, mice received the peptide 5 times a week from the 2nd month of life to death.12 In a rat colon experiment, Epitalon was given at a dose of 1 micro g, five times a week, for 6 months.13 The older-mouse tumour experiment was considerably shorter, with one-year-old female C3H/He mice kept for 6.5 months under standard conditions.3

A mouse lifetime is approximately two to three years, so these durations do not translate into human time in any straightforward way. They describe how long each experiment needed to continue to measure its particular outcome, and that is not the same as how long anybody should take the compound.

How was Epitalon administered?

animal model

Injection under the skin was the standard route in rats and mice, and injection into muscle was used in monkeys. A few studies tried other routes, and they used far smaller amounts.

One rat study delivered it through the nose, recording neuron activity for 30 minutes after doses of 30 ng per animal, a nanogram being a thousandth of a microgram.14 A companion paper used an epitalon intranasal infusion (2 ng), fifteen times less.15 Both were done in rats under anaesthetic, and both measured brain-cell firing over a few minutes rather than any longer-term effect.

Giving it by mouth has been tried in rats and changed their gut enzymes, but the abstract gives no amount, and no study among these sources measured how much swallowed peptide gets into the blood. In fruit flies, it was mixed into the food the larvae lived on. Each route is tied to its own model and its own question, which is why one cannot simply stand in for another.

Why does one paper say 1 mg and another 1 microgram?

animal model

Because the units in this literature are not always reported the same way, and a careful reader needs to check them. Two papers from the same research group, on the same strain of breast-tumour mice, give the amount differently.

One states that the mice received epithalon (Ala-Glu-Asp-Gly) in a dose of 1 mg subcutaneously.12 The other, as quoted above, gave one microgram per mouse. A milligram is a thousand micrograms, so one figure is a thousand times the other. Every other mouse study in the programme used micrograms, which suggests the milligram figure is a typing error, but the abstracts themselves do not settle it.

A third paper describing the same model writes 1 meg Vilon peptide, apparently a misprint for mcg, the usual abbreviation for microgram.16 Slips like these matter a great deal in a field where the amounts are tiny, and they are a reason to check any figure taken from these abstracts against the full paper.

Did a larger amount do more?

animal model

Not in the one experiment that varied the quantity substantially. In fruit flies, the increase in LS did not depend on the substance dose, across concentrations spanning more than three orders of magnitude.17 LS here abbreviates lifespan. A flat response of that kind is unusual, and it is a reminder that larger quantities were not demonstrated to produce larger effects.

A 2004 review of the mouse experiments by one of the investigators adds that the observed effect depended on the dose and conditions of administration, as well as genetic predisposition of the particular mice strains.18 The abstract does not specify in which direction that dependence operated.

In skin cell cultures, the stimulating effect was observed in smaller concentration diapason and level during skin ageing in old cell cultures, meaning older cells responded across a narrower range.19 None of this constitutes a dose-response relationship that could identify either a useful or a harmful quantity.

Is there a cycle or a break in the published work?

animal model

In one sense, yes, because the most common mouse schedule is itself a cycle: five days of shots, then the rest of the month off, repeated for life. That pattern was the choice of one research group, and no study among these sources compared it with giving the peptide all the time.

One rat study did look at timing, giving Epitalon only while the rats got a cancer-causing chemical, only after it, or the whole way through, and found its strongest inhibitory effect on colon tumour formation when Epitalon was continued throughout the experiment.13

That result is about colon tumours in rats given a chemical, and it compares how long the peptide was given, which is not the same as testing cycles with breaks. The human extract courses were repeated at gaps over several years, but the abstracts do not say how long each gap was. A schedule with breaks for Epitalon in people has simply not been described.

Why can't a mouse amount be converted to a person?

Because nothing among the research behind this page validates that conversion for this compound, and performing it would transform an experimental parameter into a dose. The lifelong mouse study expresses its quantity both ways, as one microgram per mouse and as approximately 30 to 40 micrograms per kilogram. It is tempting to multiply the second figure by a person's body weight.

That sum assumes the peptide is taken up, spread through the body, broken down and cleared at the same rate per kilogram in a mouse and in a person. No study among the research behind this page measured any of those properties for Epitalon, in any species. Without them, a per-kilogram figure derived from mice says nothing about a person.

The standard scaling formulas used in drug development were built for compounds whose blood levels had been measured. Applying them here would generate a precise-looking number with nothing underneath it, which is why this page reports the mouse figure and stops there.

Do cell and fly concentrations mean anything for a dose?

animal model

They describe how much peptide was added to a culture dish or a feeding mixture, which is a fundamentally different measurement from an injected quantity. In mouse egg cells, Epitalon at 0.1mM was added to the culture medium, and the cells were examined over the following 24 hours.20 In fruit flies, the substance was added to the culture medium only at the developmental stage, from egg to larva.17

A concentration in a culture dish indicates what the cells were exposed to. It does not indicate what level would be reached in blood or tissue following an injection, because none of these sources measured circulating concentrations after administration. The fly experiment is more unusual still, since the peptide was provided only before adulthood and lifespan was recorded afterwards.

These numbers matter for interpreting the individual experiments. They have no bearing on a quantity for a person.

How do you reconstitute an Epitalon vial?

Reconstitution is arithmetic, and the sum is the same for any powdered peptide. You need two numbers: the amount of powder printed on the vial, and the volume of liquid you add to it. Dividing the first by the second gives the strength in milligrams per millilitre, and multiplying by a thousand turns that into micrograms per millilitre.

The calculator at the reconstitution calculator does this from figures you supply, and it does not suggest an amount. Two cautions apply to this compound in particular. The studies above worked in micrograms and sometimes nanograms, so mixing up milligrams and micrograms gives a thousand-fold error, the same slip that turns up in the papers themselves. And the amount printed on a vial bought outside research is a claim by whoever made it, which no study on this page has checked. A printed label is not evidence of what the vial holds.