How and why silicea acts as ‘homeopathic scalpel’? To provide a scientific explanation to this phenomenon, we have to inquire deeply into the molecular properties of silica and it’s exact role in biological systems.

Silicea is known as a polycrest remedy in homeopathy. Silica, which is also known as silicea in homeopathic pharmacy, is the chemical compound silicon dioxide. It is an oxide of chemical element silicon, with the chemical formula SiO2.

Materia Medica of Silicea says: “Silica can stimulate the organism to re-absorb fibrotic conditions and scar-tissue. Ripens abscess since it promotes suppuration. Promotes expulsion of foreign bodies from tissues. In phthisis, it must be used with care, for here it may cause the absorption of scar-tissue, liberate the disease, walled in, to new activities.”

“Re-absorbing of fibrotic scar tissues, ripening, opening up and healing of abscesses by promoting suppuration, expulsion of foreign bodies from tissues”- these clinically well established homeopathic properties of SILICEA have assigned it a honorable title- “homeopathic scalpel”. Exactly, in homeopathic doses silicea causes absorption of scar tissue being part of abscess walls, and ‘liberates the contents, walled in’.

Some homeopaths prefer to use silicea as ‘homeopathic scalpel’ in ‘high potencies’- in 30c or above, where as there are others who use it as triturations- 3x, 6x etc. All of them vouch excellent results, but molecular mechanism of ‘scalpel’ actions of silicea in ‘molecular forms’ and ‘molecular imprints’ forms are entirely different, as explained later in this article.

Silica is most commonly found in nature as sand or quartz. Measured by mass, silicon makes up 27.7% of the earth’s crust and is the second most abundant element in the crust, with only oxygen having a greater abundance.Silicon is usually found in the form of complex silicate minerals, and less often as silicon dioxide or silica, a major component of common sand. Pure silicon crystals are very rarely found in nature. The silicate minerals—various minerals containing silicon, oxygen and reactive metals—account for 90% of the mass of the earth’s crust.

Ocean bed is covered by diatoms, cells of which contain large quantities of silica. Silica is the primary compound in rice husk and coconut shells. Stems of various plants, such as rice, bamboo etc also contain silica in large amounts.

Silicon is an essential element in biology, although only tiny traces of it appear to be required by animals,however various sea sponges need silicon in order to have structure. It is much more important to the metabolism of plants, particularly many grasses, and silica in the form of silicic acid act as the basis of the striking array of protective shells of the microscopic diatoms.

Diatoms, radiolaria and siliceous sponges use biogenic silica as a structural material to construct skeletons. In more advanced plants, the silica phytoliths (opal phytoliths) are rigid microscopic bodies occurring in the cell; some plants, for example rice, need silicon for their growth.Although silicon was proposed to be an ultra trace nutrient, its exact function in the biology of animals is still under discussion. Higher organisms are only known to use it in very limited amounts in the form of silicic acid and soluble silicates.

Silicon is currently considered as a “plant beneficial substance by the Association of American Plant Food Control Officials (AAPFCO). Silicon has been shown in university and field studies to improve plant cell wall strength and structural integrity,improve drought and frost resistance, decrease lodging potential and boost the plant’s natural pest and disease fighting systems.Silicon has also been shown to improve plant vigor and physiology by improving root mass and density, and increasing above ground plant biomass and crop yields.

It has been proved that Silica can bind to DNA and RNA in certain situations. Silicification in and by cells has been common in the biological world for well over a billion years. In the modern world it occurs in bacteria, single-celled organisms, plants, and animals (invertebrates and vertebrates). Examples include: ‘frustules’ of ‘diatoms’, Silica ‘phytoliths’ in the cells of many plants, practically all grasses. The spicules which form the skeleton of many primitive creatures are also rich in silica.

Crystalline silica formed in the physiological environment often show exceptional physical properties- e.g. strength, hardness, fracture toughness. Formation of the mineral may occur either within the cell wall of an organism (such as with phytoliths), or outside the cell wall, as typically happens with ‘tests’ and ‘diatoms’. Specific biochemical reactions exist for mineral deposition. Such reactions include those that involve lipids, proteins, and carbohydrates.

It is yet unclear in what ways silica is important in the nutrition of developed animal species.This remains a challenging field of research, due to its ubiquitous presence in the environment and in most circumstances it dissolves in trace quantities into the animal bodies. It certainly does occur in the living body, leaving us with the problem that it is hard to create proper silica-free controls for purposes of research. This makes it difficult for researchers to be sure when the silica present has had operative beneficial effects, and when its presence is coincidental, or even harmful.

As per latest studies, silica is recognized to play many important roles in the growth, strength, and management of many connective tissues. This is true not only for hard connective tissues such as bone and tooth.

Inhaling finely divided crystalline silica dust in very small quantities over time can lead to silicosis, bronchitis, or cancer, as the dust becomes lodged in the lungs and continuously irritates them, reducing lung capacities by inducing synthesis and accumulation of Type 1 collagen fibrils around the silica deposits. In the body, crystalline silica particles do not dissolve over clinically relevant periods of time. This effect can create an occupational hazard for people working with sandblasting equipment, products that contain powdered crystalline silica and so on. Children, asthmatics of any age, allergy sufferers, and the elderly can be affected in much less time. Even though amorphous silica, such as fumed silica is not associated with development of silicosis,but it may cause irreversible lung damage in some cases.

Continuing research of the correlation of aluminium and Alzheimer’s disease has in the last few years included the use of silicic acid in beverages, due to its abilities to both reduce aluminium uptake in the digestive system as well as cause renal excretion of aluminium.

A study which followed subjects for 15 years found that higher levels of silica in water appeared to decrease the risk of dementia. The study found that with an increase of 10 milligram-per-day of the intake of silica in drinking water, the risk of dementia dropped by 11%.

Choline stabilized silica in the form of orthosilicic acid is now used as bioavailable nutritional supplement. It has been shown to prevent the loss of hair tensile strength,have positive effect on skin surface and skin mechanical properties, and on brittleness of hair and nails, abate brittle nail syndrome,partially prevent femoral bone loss, increase collagen concentration in calves, and have potential beneficial effect on bone collagen formation in osteopenic females.

Study has shown that physiological concentration of Silica in the form of orthosilicic acid stimulates Type 1 Collagen synthesis and osteoblastic differentiation in human osteoblast-like cells in vitro. Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals,making up about 25% to 35% of the whole-body protein content. Collagen, in the form of elongated fibrils, is mostly found in fibrous tissues such as tendon, ligament and skin, and is also abundant in cornea, cartilage, bone, blood vessels, the gut, and intervertebral disc. The fibroblast is the most common cell which creates collagen. In muscle tissue, it serves as a major component of the endomysium. Collagen constitutes one to two percent of muscle tissue, and accounts for 6% of the weight of strong, tendinous muscles.

Collagen, a key component of the animal extracellular matrix, is made through cleavage of pro-collagen by the enzyme collagenase once it has been secreted from the cell. This stops large structures from forming inside the cell itself. Collagenase production can be induced during an immune response, by cytokines that stimulate cells such as fibroblasts and osteoblast, and cause indirect tissue damage. Silica is considered to play a key role in the activation of collagenase enzyme, when induced by the action of immune related signaling molecules known as cytokines.

Formation of abscesses involves a complex chain of biochemic processes induced by cytokines produced in response to immune reactions against foreign substance entering the tissues, such as foreign bodies and infectious agents. Cytokines induces chemotaxis of various immune bodies and white blood cells into the site of foreign body to fight against the intruder. A membrane is formed around the intruder by producing type 1 collagens fibrils embedded with in a layer formed of lipids, proteins and carbohydrates, which encapsulates the foreign body. This capsule ripens into an abscess by accumulation of dead white cells. Finally, once the fight is over and infection is controlled, the collagen disintegrates and the capsule breaks open to discharge the contents.

It is well understood that silica plays a role in the process of membrane formation and encapsulation by promoting the production of type 1 collagen fibrils. Exact molecular mechanism of this role is not well understood yet. May be by acting as co-factors in activating collagenase enzyme to cleavage pro-collagen into collagen, which is the basic building material of capsular membrane of abscesses and cysts. Silicon is also considered to act as a hardening and stabilizing agent of collagen fibrils. During stage of ripening of abscesses, as concentration of inflammatory cytokines decrease, silicea also gradually decreases in collagen fibrils, thereby helping the disintegration of capsular membrane and opening up of abscesses.

Bilologically available crude silica particles help the process of formation of cysts and indurations around foreign bodies, presumably by supplying silicon ions to activate collagenase enzyme in the build up of type 1 collagen and capsular membranes. Silicon also infiltrates into cyst walls, and act as a structural ingredient. That is why silicosis develops in lungs due to accumulation of silica particles.

Triturated forms of silica below 12c contain ionized silica particles, which are highly activated by breaking of intermolecular bonds during process of trituration. These activated particles can compete with biological silica molecules in binding to collagen fibrils, there by resulting in removal of silica and inducing ripening of abscesses. But we should remember, using of these molecular forms of activated silica may pose dangerous to the organism, as they will create off-target molecular inhibitions and unexpected pathologies in various biochemical pathways in the organism.

Silica potentized above Avogadro limit contains only ‘molecular imprints’ of silica, without any silica molecules present. Due to complementary configuration, these molecular imprints can bind only to off target excess biological silica molecules , there by removing them from the collagen matrix, and helping in their disintegration, leading to easy maturation and opening up of abscess walls.

Potententized silica contains only ‘molecular imprints’, which cannot bind to any biological targets except off target silica. As such, they are safe to be used as ‘homeopathic scalpels’ without any fear of unwanted side effects.

It is the biological role of silicea as a cofactor in the synthesis of type 1 collagen, and its property of getting embedded in collagen fibrils that makes it an effective homeopathic therapeutic agent in potentized forms in many pathological conditions such as abscesses, indurations, cysts, skin problems, nail problems, joint problems, keloids etc etc.

This is only a humble introductory study on silica biochemistry in relation with its role in abscess formations. There remains a lot to be researched, explored and explained on this topic. A lot of questions yet remain to be answered.


CONVENTIONAL HOMEOPATHS approach modern SCIENCE from the standpoint of ORGANON, where as SCIENTIFIC HOMEOPATHS learn ORGANON from the standpoint of modern SCIENCE. It makes all the difference in their approaches, perspectives, paradigms and methods of practice.

According to CONVENTIONAL homeopaths, anything you say about homeopathy should be FITTING to the ‘aphorisms’ of ORGANON. Otherwise, you will not be a ‘true’ homeopath!

There are many things in ORGANON that does not agree with modern scientific knowledge. There are many things that are totally UNSCIENTIFIC. As such, you cannot talk SCIENTIFIC HOMEOPATHY in a way ‘fitting’ to the ‘aphorisms’ of ORGANON. You cannot make homeopathy a MEDICAL SCIENCE if you are not ready to abandon those unscientific things we were so far taught as part of ‘fundamental principles’ of homeopathy.

I am not talking about ‘aphorisms’ or ‘beliefs’. I am talking about my rational interpretations of similia similibus curentur, based on modern scientific knowledge of life, disease, drugs and cure.

Please note, nothing is said in organon about MOLECULAR IMPRINTING also.

If you think we should talk about homeopathy only in terms of ‘aphorisms’ written 200 years ago when scientific knowledge was in its primitive state, you cannot even think about ‘molecular imprints’ active factors of potentized drugs. You cannot talk about genetics, enzymes, ligand-receptor kinetics, antibodies , molecular pathology or anything like that. According to you ‘true’ homeopathy should be mere repeating of aphorisms in organon! You will feel ‘very very very sorry’ when somebody says something that do not fit to ‘aphorisms’.
Many homeopaths believe POTENTIZATION is a process of ‘dividing’ drug substance into smaller fractions, ultimately ‘converting’ them into ‘energy’, and transferring the ‘dynamic energy’ so released into sugar of milk or rectified spirit. Nobody so far taught them to think about potentization in terms of MOLECULAR IMPRINTING.

Exactly, what is the ‘fundamental principle’of homeopathy? A principle that forms the essential basis of homeopathic therapeutic system? I think there is a lot of confusion over the subject of ‘fundamental principles of homeopathy’, not only among homeopaths, but even our ‘theoreticians’.

In my opinion, the therapeutic principle of ‘similia similibus curentur’ is the only ‘essential’ fundamental principle of homeopathy. ‘Potentization’ is not a fundamental principle, but a practical way of preparing homeopathic drugs. Other ‘theories’ are only philosophical explanations, conjectures, interpretations, opinions and empirical conclusion based on personal experiences of ‘stalwarts’ and ‘masters’. They are not ‘fundamental principles’ of homeopathy.

Some people consider each and every word uttered by our ‘master’ as ‘fundamental principles’ of homeopathy. They would profusely quote his words from ORGANON whenever some body raises any hard questions. Some others would even include the words of other ‘stalwarts’ like Kent, Herring and the like also in the category of ‘fundamental’ principles. They would declare that whatever ‘master’ and other ‘stalwarts’ said 200 years ago were “most scientific” and should not be changed. They would not tolerate any attempt of re-reading those ‘theories’ in the light of scientific knowledge humanity has amassed during last two centuries after Hahnemann lived on this earth.

Even though Hanemann was indeed a great genius and visionary, it is impossible for anybody to proceed with his intellectual quest without drawing resources from the treasures of knowledge amassed by previous generations. Obviously, no genius can totally overcome the objective limitations imposed upon him by the space-time context of his life and activities.

We should never forget the objective historical context of 18th century Germany, where Samuel Hahnemann lived and developed his novel therapeutic system. Hahnemann had developed his ideas depending upon the existing knowledge about the universe available to him. It is not to be seen as a sin to say that his thoughts and words were more or less confined by the limitations imposed by the infantile level of science and technology then existed there. Even though the essence of the therapeutic principle he developed is capable of transcending the boundaries of centuries to come, it would be unfair to try to evaluate his achievements and contributions detached from his objective time-space framework.

Had Hahnemann happened to live in this world 200 years later, the towering genius of Hahnemann would have presented to humanity a therapeutic system totally different, and much more advanced and scientific than what we now call Homeopathy. He would have definitely rewritten completely what we preach and practice in the name of Homeopathy today.

Whenever we try to learn the teachings of Hahnemann, we should be on the look out to understand what he would have said about those subjects, if he were elaborating them in the modern context. We should not take his written words as if they were ultimate immutable truth, unquestionable and beyond any scope of further revisions and improvements. We should honor the great master by following his teachings as valuable guide to tread forward, and not as lifeless dogmas.

If Samuel Hahnemann happened to live among us now, he would have mastered all the latest scientific knowledge available. He would be the greatest scientist of our era. He would explain “similia similibus curentur” on the basis of quantum theory, modern biochemistry and the latest understanding of molecular dynamics of disease and therapeutics. He would have explained “potentization” on the basis of modern ‘molecular imprinting’, and would have devised a more sophisticated and scientific method of molecular imprinting to replace the present process of potentization.


Homeopaths use to talk all sorts of totally absurd and irrational theories and baseless claims about homeopathy, and when asked for scientific proof, they will declare that it is the duty of scientists to prove all those things.
Scientists can prove and explain only what is really scientific in homeopathy. Do not expect science to justify all those nonsense beliefs of homeopaths regarding vital force, dynamic drug energy, dynamic miasms, healing energy, potencies, mesmerism and other innumerable fanciful ideas propagated as ‘fundamental principles’ of homeopathy. Nobody can prove them!

High dilution homeopathic cure involved in ‘similia similibus curentur’ is an objective natural phenomenon, and science has to explain it in terms of modern scientific paradigms and methods of biological sciences and pharmacology. That means, science has to find out what are the active principles drugs diluted above avogadro limit, and explain its therapeutic actions using a biological model that fits to modern scientific knowledge system. 

Only when modern scientists succeeds in that job, homeopathy will get recognized as a branch of modern scientific medicine. In that process, homeopathy will have to discard all its unscientific beliefs and notions from its theoretical system, and mercilessly throw away most of its most revered innumerable volumes of ‘literature’ into the archives of medical history.
Most homeopaths are deeply obsessed with ideas such as ‘vital force’, ‘dynamic energy’, and many other superstitious beliefs. They cannot imagine a homeopathy devoid of such ideas, principles and laws, which are according to them ‘immutable’! They fear the whole system of homeopathy would fall down if these ‘basic principles’ are not safeguarded, as they are deemed to be the foundation of homeopathy. They fight tooth and nail to defend their absurd and unscientific ‘theories’ which challenge the common sense of even a common man.
They cannot tolerate anybody criticizing the ‘master’ or pointing out any mistakes in any of his aphorisms. According to them, if anything is found in aphorisms that disagree with modern scientific knowledge, it is due to the ‘limitations’of science, as the master is ‘beyond’ any mistakes or limitations! It is the duty of scientists to change their methods and update their knowledge so as to fit to the ‘ultimate’ science of homeopathy created by Hahnemann! 

These faithful ‘hahnemannians’ hope that a day will come when all their ‘beliefs’ and fancies are ‘proved’ scientifically. They believe that modern science is presently lagging much behind homeopathy, and they wait for science to advance so that scientists can understand and accept the theoretical blunders promoted by modern gurus as homeopathy!

The concept of ‘vital force’, on which the whole philosophical system of homeopathy is built up on, stands as a formidable stumbling block in its way of harmony with modern science and its methodology. The theoretical system of Hahnemannian homeopathy is based on the spiritual oncept that there is an abstract ‘vital force’ alien to the physical body, existing as a part of ‘universal force’ which enters the body and possess to enliven it, and leaves it with the advent of death. Homeopaths perceive diseases as disordered states of this ‘vital force’, and believe that it is only on this “immaterial, conceptual level of ‘vital force’ that the cure of diseases might take place.

Whatever be one’s philosophical world out look,  at least when dealing with a science of therapeutics, we have to be capable of replacing the concept of ‘vital force’ with a more rational expression, ‘vital process’, if we could discuss homeopathy as a system of scientific medicine. ‘Vital  processes’ exist through complex chains of interconnected molecular interactions known as biochemical pathways. A state of disease is created through some or other deviations in these normal biochemical processes. Hence, according to our scientific perspective, every pathology starts as an error at the molecular level. We cannot proceed further with our scientific discourse on homeopathy, without recognising at this fundamental position of modern science. Scientists belonging to various disciplines, engaged in the study of various natural phenomena, adopt such a practical stand even if ideologically they happen to be absolute spiritualists. It is impossible even for a most ‘spiritualist’ nuclear physicist to engage himself in his particular research activities, viewing the atoms, sub-atomic particles or forces as mere ‘spiritual entities’. The homeopathic theoreticians also should at least follow this example. They should be able to deal with phenomena of life, disease, therapeutics, and medicinal substances primarily as material substances and processes. It would be better for homeopathy at large, if these ‘masters’ and ‘gurus’ of homeopathy could confine themselves to a scientific vocabulary, refraining from mixing it up with unnecessary spiritualistic and philosophical jugglery of words such as ‘vital force’ and ‘non-corporeal’ ‘dynamic power’, while talking about a scientific theory of therapeutics.

 Using medicinal agents having specific material qualities, we can deal with these ‘vital processes’ only at the material level. It is an absurdity to think that physicians are dealing with an ‘immaterial’, ‘spirit-like’ ‘vital force’, that too, using instruments and medicinal agents of purely material nature. If homeopathic physicians were dealing with ‘immeterial dynamic forces’, instead of using ‘material medicines’, they could have done it better through prayers, ‘pujas’ and other occult practices!

The argument that homeopathic drugs act not by their ‘material qualities’, but by an ‘immaterial’ medicinal force, called ‘dynamic force’ is nothing but absurdity. Would these theoreticians agree that this so-called ‘dynamic power’ of individual drugs’ are determined by the specific ‘material’ properties of their constituent molecules? It is undeniable fact that this so-called ‘dynamic power’ varies from drug to drug, depending up on their molecular level structure and composition. If we were dealing with an immaterial ‘vital force’ and ‘dynamic power’, why should we use all those different types of drugs existing in homeopathy? While talking about ‘immaterial’ ‘spirit-like’ ‘dynamic healing power’, ‘liberated’ through potenization, which can be carried in corked bottles and swallowed as sugar pellets, we should be aware, how much homeopathy would become a laughing stock in the eyes of scientific community. If we still continue to claim that there is a ‘spirit-like’ force in homeopathic medicines, independant of their material qualities, a ‘force’ that is soluble in water and alcohol, that could be transferred from bottles to bottles, acts on the ‘vital force’ when applied on tongue, lost when subjected to physical forces such as heat or electricity, how can we engage in a scientific dialogue? What type of ‘liberated’ ‘non-corporeal ‘dynamic force’ is we talking about?

We have to be well aware that the theory of ‘vital force’ was adopted by Hahnemann from the vitalistic philosophy then existed in Europe. Since modern material science was only in its rudimentary stage, he was not able to explain the phenomena he observed, in scientific terms. Due to inescapable historical limitations, he was naturally compelled to accept some sort of vitalistic explanations for his new inventions.

Now, we live in a new era of enlightenment, totally different from that of Hahnemann. Modern science has unravelled the molecular processes of life and diseases to such a level that we can logically explain the fundamental principles of homeopathy on a new scientific basis. It is an unpardonable injustice done to the great genius of Hahnemann, if we still continue to stick on to his obsolete unscientific explanations. We should exhibit the intellectual courage to mercilessly discard the evidently irrational parts of Hahnemannian homeopathy. Same time, we should safeguard its inner kernel of the great natural therapeutic law of ‘similia similibus curentur’ and therapeutic application of ‘molecular imprints’, which our master called ‘potentized’ drugs. We should bravely replace the concept ‘vital force’ with scientific understanding of ‘vital process’.

As long as ‘classical’ homeopaths continue to cling to their unyielding stand that homoeopathy is a ‘complete-in-itself’ philosophical and therapeutic system, beyond any scope for change and development, I find no chance for a meaningful scientific dialogue to happen. Claiming homeopathy to be a ‘science beyond science’, or ‘post-modern science’ may help somebody to appear fashionable, but they should realize that all these exercises contribute a lot in enstranging this great therapeutic system from main stream science.

Main challenge we face when attempting to offer a scientific explanation for homeopathy is that these homeopathic theoreticians make the situation more and more complicated by mixing up the basic concepts regarding life, disease, drugs and therapeutics, with their idealistic philosophical speculations and unscientific spiritualistic world outlook.

From the very onset, we have to adopt following fundamental factors as the basis of our intellectual inquiry:

Therapeutics is a totally materialistic activity. If we do not agree upon at least this much of fundamental propositions, no meaningful discussion will be possible regarding scientific understanding homeopathy.

Since we are now competent to offer a scientific molecualar interpretation of ‘similia similibus curentur’, and ‘potentization’, the main fundamental principles of homeopathy, there is no need for relying upon the obsolete vitalistic explanations and speculations of Hahnemann, based on the concept of ‘vital force’ and ‘non-cprporeal’ ‘spirit-like’ ‘dynamic medicinal force’. Instead of repeating the unscientific concept of ‘dynamic medicinal force’, we can now logically explain the homeopathic potencies on the basis of ‘molecular imprinting in water’.
The concept of vital force belongs to the pre-scientific era of medical philosophy. During that period, nothing was known about the material basis of vital processes. Modern biochemistry and knowledge of complex biological molecules and biochemical processes were unknown. The wonderful phenomena of life were considered to be due to an immaterial, spirit-like vital force that ‘animates’ the body during life, and leaves the body during death. Vital force was believed to exist even without a body, and disease was considered to be due to some deviations in this ‘dynamic’ vital force. This idea was the basis of all sorts of ‘spiritual helaing’ practices of the primitive society.

Hahnemann also used this ‘vital force’ philosophy in building his homeopathic theortical system, since he could not explain the phenomenon of high dilution therapeutics by any other way. 

The idea of ‘vital force’ has no any role in modern biological sciences or pharmacology. We cannot even reasonably communicate with scientific community unless we discard this unscientific concept from the paradigms of homeopathic therapeutics.


Homeopaths should build up a habit of exploring deeper into the knowledge regarding drug substances than what we get from our material medica books. It is essential to understand about the constituent chemical molecules contained in the drug substances, as well as the biological targets to which they bind in our body when applied as a medicinal agent. Then only we can scientifically know how the drug substances produce “drug symptoms” during proving, and how they remove diseases according to the principle “similia similibus curentur “.
To begin with such a study, let us take up SEPIA as an example first. Homeopathic drug SEPIA is the INK of CUTTLEFISH. Cuttlefish are marine animals of the order Sepiida. They belong to the class Cephalopoda, which also includes squid, octopuses and nautiluses. Despite their name, cuttlefish are not fish but molluscs.

Cuttlefish are sometimes referred to as the “chameleons of the sea” because of their remarkable ability to rapidly alter their skin color at will. Cuttlefish change color and pattern, including of light polarisation and even texture to communicate to other cuttlefish, to camouflage themselves, and in deimatic display to warn off potential predators.

SEPIA INK is a dark pigment released into water by most species of cephalopod, usually as an escape mechanism. 

The ink is released from the ink sacs located between the gills, and is dispersed more widely by accompanying its release with a jet of water from the siphon. Its dark color is caused by its main constituent, melanin. 

Each species of cephalopod produces slightly differently coloured inks; generally, octopuses produce black ink, squid ink is blue-black and cuttlefish ink is brown.

SEPIA ink contains a number of chemicals in a variety of different concentrations, depending on the species. However, its main constituents are MELANIN and mucus. It can also contain, among other things, tyrosinase, dopamine and L-DOPA, and small amounts of amino acids, including taurine, aspartic acid, glutamic acid, alanine and lysine. SEPIA INK also contains large amounts of aquatic minerals suchas iodine, sodium, fluorine, iodine etc absorbed from sea water in which they live. 

When potentized, SEPIA contains MOLECULAR IMPRINTS of all these constituent chemical molecules, which are the active principles of potentized SEPIA. 

In molecular biology, Tyrosinase refers to an oxidase, which is the rate limiting enzyme for controlling the production of melanin. It is mainly involved in two distinct reactions of melanin synthesis; firstly, the hydroxylation of a monophenol and secondly, the conversion of an o-diphenol to the corresponding o-quinone. o-Quinone undergoes several reactions to eventually form melanin. Tyrosinase is a copper-containing enzyme present in plant and animal tissues that catalyzes the production of melanin and other pigments from tyrosine by oxidation, as in the blackening of a peeled or sliced potato exposed to air. It is found inside melanosomes.

A mutation in the tyrosinase gene resulting in impaired tyrosinase production leads to type I oculocutaneous albinism, a hereditary disorder. 
Tyrosinase activity is very important. If uncontrolled during melanoma, it results in increased melanin synthesis. Several polyphenols including flavonoids or stilbenoid, substrate analogues, free radical scavengers and copper chelators have been known to inhibit tyrosinase.  

MOLECULAR IMPRINTS of tyrosinase molecules contained in potentized SEPIA can remove the molecular errors caused by various types of INHIBITORS that cause certain types of albinism, leucoderma and hypopigmentations.

MMOLECULAR IMPRINTS of certain chemical constituents of SEPIA act homeopathically by binding to the pathogenic molecules that inhibit MELANOCORTIN RECEPTORS in melanocytes, which are the natural binding sites of MELANOCYTE STIMULATING HORMONES that induce production of MELANIN, the skin pigment of our body

MELANOCORTIN RECEPTORS lie within the cell membrane, and is signalled by melanocyte-stimulating hormone (MSH) released by the pituitary gland. When activated by MSH, it initiates a complex signaling cascade that leads to the production of the brown or black pigment eumelanin. In contrast, the receptor can also be antagonized by agouti signalling peptide (ASIP), which reverts the cell back to producing the yellow or red phaeomelanin.

MOLECULAR IMPRINTS of melainin, dopamine and L-DOPA, taurine, aspartic acid, glutamic acid, alanine and lysine, iodine fluorine, bromine sodium etc contained in potentized SEPIA decide the diverse types its homeopathic therapeutic actions when used according to SIMILIA SIMILIBUS CURENTUR..

We have to study all drugs of homeopathy in this way, if we want to make theory and practice of homeopathy really scientific and rational.


Dear skeptic, if you are not biased and blindly prejudiced against homeopathy, and is a genuine seeker of truth, instead of “killing ” homeopathy on clubhouse and other social media platforms, kindly look around with your eyes open to reality.

Please find some time to visit a few homeopathic clinics in your city and see the patients waiting there, ask them about their experiences with homeopathy. Do not be under the notion that all those people are misguided uneducated ignorant folks- you will of course meet a lot of very rational, science-conscious, highly educated and socially well-placed people there. You can get first-hand information about hundreds of genuine homeopathic cures from them, if you are genuinely interested to know.

You are talking a lot about ‘dangers and deaths caused by homeopathy’. Do you know how many people allopathy kill or make chronically ill everyday around the world? Do you know, high dilution drugs used in homeopathy do not contain any drug molecule, and hence cannot produce any harmful effects upon living body? 

You are saying that all beneficial effects attributed to homeopathy are only placebo effects. Dear sir, if placebo effects are real, will you agree, most of the beneficial effects attributed to allopathy medicines are also due to placebo effects? If not, will you scientifically explain, why placebo theory is applicable to homeopathy only, and not to allopathy medicines? Using your placebo theory, how will you explain those thousands of homeopathy cures produced in small children, livestock and even plants?
If you are ‘not aware’, of ‘evidences for homeopathy’, where from you got ‘evidences against’ homeopathy? How can you utilise your “lack of your knowledge” regarding homeopathy as an evidence against homeopathy?

How can you say homeopathy is a ‘superstitious health belief’? From my 50 years of observations, I am fully ‘aware’ that homeopathy really works. Give me 15 genuine patients with different acute and chronic diseases, to get treated by our homeopathic medical team. I will convince you by 15 days that homeopathy is not placebo or fake.

You always start your arguments from the blind ‘belief’ that homeopathy is ‘placebo’ and ‘quackery’, and you don’t want to know the truth through experiments. Do you think your ‘lack of awareness’ is enough evidence to disprove homeopathy?

You cannot declare homeopathic cure is scientifically implausible, only on the reason that homeopaths are talking a lot of implausible theories about homeopathy. We can change the wrong theories. Scientific theories about homeopathy are gradually evolving. Learn to differentiate between objective homeopathic cures and unscientific subjective theories currently going around about homeopathy.

It is true that theoretical system of homeopathy contains a lot of unscientific ideas, since they were evolved during a period when modern scientific knowledge was in a very primitive state. Due to this historical limitations, Hahnemann could not obviously explain all his truthful observations regarding disease and cure in scientific terms. But wrong explanation does not make a true observation of a natural objective phenomenon untrue. If an existing explanation of a phenomenon is wrong and unfitting to our scientific knowledge, scientific temper demands us to formulate new explanations that are fitting to advance knowledge environment. As per scientific method, limitations of a theory cannot be considered as an evidence to disprove the existence of a phenomenon as such. If theoretical system of homeopathy is wrong, what scientific community has to do is formulate a new theoretical system for explaining homeopathy, in a way fitting to advanced scientific knowledge.

Skeptics have every rights to criticise homeopathy. It is quite natural that anybody equipped with minimum basics of modern scientific knowledge will say ‘homeopathy is scientifically implausible’, if he happens to get introduced to only ‘theoretical\” part of homeopathy, which consistis of a lot of unscientific and ridiculously superstitious ideas.

Same time, skeptics should know, in spite of the ‘scientifically implausible’ theoretical system, the phenomenon of high dilution therapeutics and ‘similia similibus curentur’ involved in homeopathy observed by Hahnemann remains an objective truth proven by thousands of wonderful cures happening every day, which the master failed to explain scientifically due to the historical limitations of knowledge available to him. 

My request to scientific community is, please do not fail to differentiate between the unscientific ‘theoretical system’ of homeopathy, and the objective natural phenomenon involved in homeopathic cure.

Homeopathy could be made acceptable to scientific community, only if homeopaths succeeded in explaining and proving the objective truth involved in it using advanced scientific knowledge and methods, discarding all those unscientific ideas such as “vital force” and “dynamic energy”.


We cannot make homeopathy established as a scientific medicine without discarding the concept of vital force from its theoretical system.

Vitalism is an unscientific philosophical stream that is based on the belief that “living organisms are fundamentally different from non-living entities because they contain some non-physical element or are governed by different principles than are inanimate things”.

Where vitalism explicitly invokes a vital principle, that element is often referred to as the “vital spark”, vital force, “energy” or “élan vital”, which some equate with the soul.

In the 18th and 19th centuries vitalism was discussed among biologists, between those who felt that the known mechanics of physics would eventually explain the difference between life and non-life and vitalists who argued that the processes of life could not be reduced to a mechanistic process.

Some vitalist biologists proposed testable hypotheses meant to show inadequacies with mechanistic explanations, but these experiments failed to provide support for vitalism.

Biologists now consider vitalism in this sense to have been refuted by empirical evidence, and hence regard it either as a superseded scientific theory, or, since the mid-20th century, as a pseudoscience.

Vitalism has a long history in medical philosophies: many traditional healing practices posited that disease results from some imbalance in vital forces.

The notion that bodily functions are due to a vitalistic principle existing in all living creatures has roots going back at least to ancient Egypt. In Greek philosophy, the Milesian school proposed natural explanations deduced from materialism and mechanism.

However, by the time of Lucretius, this account was supplemented, and in Stoic physics, the pneuma assumed the role of logos. Galen believed the lungs draw pneuma from the air, which the blood communicates throughout the body

Vitalism has a long history in medical philosophies: many traditional healing practices posited that disease results from some imbalance in vital forces.

In the Western tradition founded by Hippocrates, these vital forces were associated with the four temperaments and humours; Eastern traditions posited an imbalance or blocking of qi or prana. One example of a similar notion in Africa is the Yoruba concept of ase. Today forms of vitalism continue to exist as philosophical positions or as tenets in some religious traditions.

Complementary and alternative medicine therapies include energy therapies, associated with vitalism, especially biofield therapies such as therapeutic touch, Reiki, external qi, chakra healing and SHEN therapy. In these therapies, the “subtle energy” field of a patient is manipulated by a practitioner. The subtle energy is held to exist beyond the electromagnetic energy produced by the heart and brain. Beverly Rubik describes the biofield as a “complex, dynamic, extremely weak EM field within and around the human body….”

The founder of homeopathy, Samuel Hahnemann, promoted an immaterial, vitalistic view of disease: “…they are solely spirit-like (dynamic) derangements of the spirit-like power (the vital principle) that animates the human body.” The view of disease as a dynamic disturbance of the immaterial and dynamic vital force is taught in many homeopathic colleges and constitutes a fundamental principle for many contemporary practising homeopaths.

Francis Crick, the co-discoverer of the structure of DNA, stated “And so to those of you who may be vitalists I would make this prophecy: what everyone believed yesterday, and you believe today, only cranks will believe tomorrow.”

While many vitalistic theories have in fact been falsified, notably Mesmerism, the pseudoscientific retention of untested and untestable theories continues to this day. Nearly all the pseudoscientific systems are based philosophically on vitalism, and mainstream science has rejected vitalism since at least the 1930s, for a plethora of good reasons that have only become stronger with time.


One of the monumental mistakes happened to Hahnemann due to the primitive state of scientific knowledge available during his time was that potentized medicines act upon the body through “sentient” or sensory nerves.

In aphorism 16 of Sixth Edition of organon, he says:

“all such morbid derangements (diseases) cannot be removed from it by the physician in any other way than by the spirit-like (dynamically #your new , virtual) alterative powers of the serviceable medicines acting upon our spirit-like vital force, which perceives them through the medium of the sentient faculty of the nerves everywhere present in the organism”.
Here Hahnemann says that vital force “perceives” the “powers” of medicines through “sentient faculty of nerves”. According to this view, vital force is an intelligent conscious immaterial entity governing the living body and constantly “perceiving” through “faculty of sentient nerves” everything happening around. From modern scientific view, this idea is totally absurd and unscientific. Various in vivo studies have already proved that potentized homeopathic medicines can chemically interact with biological molecules even in the absence of vital force, sentient nerves or a brain to which the information are carried by “sensory nerves”.  Actually, there does not exist any particular “power” in medicinal substances that could be “perceived by vital force”, but the medicinal properties of drug substances are nothing but their capacity to interact with specific targets in biological molecules in our body due to the peculiar structure and conformations of individual chemical molecules they contain. Chemical molecules cannot travel through sensory nerves to brain, but only sensory information is transmitted as electric impulses. 

In aphorism 272 of Sixth Edition:

“placed dry upon the tongue, is one of the smallest doses for a moderate recent case of illness. Here but few nerves are touched by the medicine. A similar globule, crushed with some sugar of milk and dissolved in a good deal of water and stirred well before every administration will produce a far more powerful medicine for the use of several days. Every dose, no matter how minute, touches, on the contrary, many nerves.”
Here also, Hahnemann talks about the importance of medicinal substances direct “touching” the nerves as a pre-condition for eliciting a therapeutic action. 

Again in aphorism 285 of Fifth Edition:

“nerves of the living organism can be touched, whereby the power of the medicine is certainly also communicated to the whole organism”
See aphorism 286 of Fifth Edition:

“when the medicine is taken, it comes in contact with a much larger surface of sensitive nerves responsive to the medicinal action. “

Aphorism 288 Fifth Edition:
The action of medicines in the liquid from upon the living human body takes place in such a penetrating manner, spreads out from the point of the sensitive fibers provided with nerves whereto the medicine is first applied with such inconceivable rapidity and so universally through all parts of the living body, that this action of the medicine must be denominated a spirit-like (a dynamic, virtual) action.
By this statement, Hahnemann has clearly demonstrated how much ignorant he is regarding the structure and functioning of nervous system. He seems to think that information can “spread out” to all parts of body “from the point of the sensitive fibers provided with nerves whereto the medicine is first applied”! Actually, each sensory nerve in any part of the body is connected only to brain, and information collected by nerve endings are transmitted directly to brain through system of  electric impulses and neurotransmitters, where it initiates some bio molecular interactions . Sensory information is never “spread out” ‘‘from the point of the sensitive fibers provided with nerves whereto the medicine is first applied”.

Hahnemann continues in same aphorism as follows:
“In little children it may be applied close to their nostrils whilst they are asleep with the certainty of producing an effect. The medicinal aura thus inhaled comes in contact with the nerves in the walls of the spacious cavities it traverses without obstruction, and thus produces a salutary influence on the vital force”. 
Everybody knows well how inhalation of toxic gases produce toxic effects upon the body. Molecules of toxic substances thus inhaled are always detectable in the blood samples of the individual, which clearly demonstrates that they enter the body through blood capillaries in the mucous membranes of upper and lower respiratory tract, and not through “sensory nerves”. 
Hahnemann’s advice on another occasion regarding application of potentized medicines to infants through nursing mothers or wet nurses actually contradicts his theory that drugs act through “sentient nerves”. Medicines taken by nursing mother could be transferred to infant only though breast milk, which does not contain any “nerve fibre”! 
From scientific point of view, molecular imprints contained in potentized drugs applied in mouth are absorbed into blood stream through capillaries in buccal mucosa. 

Substances absorbed through the buccal mucosa will bypass gastrointestinal enzymatic degradation and the hepatic first-pass effect, since they are directly drained into systemic circulation through superior vena cava. The mouth has a relatively large area for drug application and good accessibility compared to the nose, rectum, and vagina. In particular, the sublingual and buccal mucosal regions are highly vascularized and, therefore, are useful for systemic drug delivery. Sublingual administration involves placing a drug under the tongue and buccal administration involves placing a drug between the gums and cheek. The sublingual and buccal routes are considered by modern medicine also as promising alternatives to the traditional oral and parenteral routes for drug delivery.

The oral cavity has a relatively neutral pH of approximately 6.2 to 7.4, and has limited enzymatic activity. The surface area of the oral mucosa is relatively small (100–200 cm2), with the sublingual and buccal regions having an estimated surface area of 26.5 ± 4.2 cm2 and 50.2 ± 2.9 cm2, respectively. These regions in the oral cavity are lined by non-keratinized, stratified squamous epithelium that is 100–200 µm and 8–12 cells thick in the sublingual region, and 500–800 µm and 40–50 cells thick in the buccal region. Components from the saliva also binds to the surface of the buccal and sublingual epithelium to create a mucus layer with an average thickness of 70–100 µm. Underneath the epithelium is the lamina propria and submucosa that consists of connective tissue with a network of blood vessels, lymphatic vessels and smooth muscles. Molecular imprints contained in potentized can be rapidly and directly absorbed into the systemic circulation via venous drainage to the superior vena cava.

The sublingual and buccal routes of administration have a number of advantages, for systemic drug delivery of modern medicines. In general, they produce faster onset of action compared to orally ingested drug formulations. Drug absorption is relatively faster across the sublingual mucosa compared to the buccal mucosa due to the thinner epithelium. In addition to rapid absorption, the portion of drug that is absorbed through the blood vessels directly enters the systemic circulation and bypasses hepatic first-pass metabolic processes. Therefore, this route is particularly useful for highly soluble drugs that undergo high hepatic clearance or decomposition in the gastrointestinal tract. The non-adherent saliva in the buccal and sublingual regions also contains less mucin and limited enzymes such as salivary amylase. Drugs may also be more stable owing to the pH in the mouth being relatively neutral compared to other parts of the gastrointestinal tract.

Absorption of potentized drugs from mouth cavity is highly dependent on the residence time of the drug in the sublingual and buccal area. This may vary considerably depending on the dispensing vehicle we use. The dispensing vehicle should be ideal for providing enough residence time to ensure optimal disintegration and drug absorption. In addition, the dispensing vehicle  should increase the residence time of the formulation in the sublingual or buccal region to optimize drug permeability and systemic absorption. In addition, patients should avoid eating, drinking, chewing, or swallowing until the medication has been absorbed. Swallowing the medication will decrease the drug’s effectiveness.Holding the medicines in mouth without swallowing for some time will surely facilitate better absorption and drug action.
Potentized drugs are absorbed from baccal cavity very easily, since they have  a good balance between hydrophilic and lipophilic properties, being constituted by water and alcohol molecules. That is, they are easily soluble in aqueous buccal fluids and also have high lipid solubility to be able to cross the epithelial membrane in these regions, which is usually by passive diffusion. Habit of smoking can decrease the sublingual or buccal absorption of medications due to vasoconstriction of the blood vessels.

The pH of the saliva is ideal for perfect absorption of potentized homeopathic drugs. Molecular imprints may undergo passive absorption pathways via transcellular diffusion or paracellular diffusion, depending on the size of molecular imprints. It should be noted that the pH of the saliva can be temporarily altered by environmental factors such as foods and drinks, or personal factors such as oral diseases, which can affect the sublingual and buccal absorption of drugs.
Saliva flow can influence buccal and sublingual drug delivery by altering the rate of disintegration of the formulation and dissolution of the drug. For example, if the mouth is dry, this can negatively affect drug absorption. Conversely, if saliva flow is considerable, this can lead to the drug being swallowed before absorption.

Does Peer-Review Guarantee The Correctness of Conclusions of a Research Paper?



Many people believe that peer-reviewed papers published in journals are ultimate proofs for the correctness of interpretations and conclusions of a Research paper.

Actually, peer review is a process used to determine an academic paper’s “suitability for publication”.

Peer review does not guarantee correctness of a theory, but guarantees only that the format, language, arrangement, organization and presentation of a “paper is suitable for publication”.

We all know there are thousands of peer reviewed articles published in various journals proposing many absurd theories about homeopathy.

Wikipedia says: “Peer review is generally considered necessary to academic quality and is used in most major scientific journals, but it does by no means prevent publication of all invalid research.”

Please note, peer review “does by no means prevent publication of all invalid research.”!

Publishing a Peer reviewed article does not mean that the ideas proposed in the article are true and beyond any criticism.

Nobody here questions the claim that the researchers detected nano-sized particles of some elements. What we ask is for an explanation regarding the source of this particles, as well as their role in the therapeutic properties of potentized drugs.

Here I am sharing two slides presented at a “scientific seminar” by a “homeopathy scientist” regarding his ‘nanoparticles study’ of AURUM METALLICUM. His work is also published in a peer reviewed journal!

Watch both slides carefully. It is said that potentized aurum met contains ‘nanoparticles’ containing Aurum, Aluminium, Silica, Pottassium, Ferrum, Cuprum, Indium, Hafnium, Sodium, Chlorine, Boron, Cobalt and Carbon, along with ‘Quantum Dots’.

Nanoparticles detected in Aurum Met contains Aurum in following ratios:

6C contains 2.82%, 30C contains 89.06%, 200C contains 12.14%, 1M contains 1.24%, 10M contains 24%, 50M contains 9.73 %, CM contains 6.58% of elemental aurum.

15.63% of ALUMINIUM is present in nanoparticles detected in Aurum Met 1M. But other potencies of Aurum met does not contain any ALUMINIUM.

Where from this aluminium came in aurum met 1m only, which was not present in 6c, 30c, 200c, 10m or cm?

See the fun.Nanoparticles detected in Aur met 1m contains only 1.24% aurum, where it contains 15.63% aluminium.

If ‘nanoparticles are active principles of AURUM MET 1M, does it act by 15.63% aluminium or 1.24% aurum?

If AUR MET 6C contains AUR 2.82% and CUPRUM 75.82%, which will be the active principles? CUPRUM or AURUM?

If AUR 200 contains AURUM 12.14%, POTTASSIUM 29.36%, CUPRUM 25.8%, and SODIUM 20.08%, how can you say AURUM NANOPARTICLES are the active principles of Aur Met 200?

If AUR MET 50M contains AURUM 9.73% , CUPRUM 53.27%, and COBALT 23%, how can you say it is AURUM MET? Rather callit and use it as CUPRUM MET?

If AURUM MET CM contains AURUM 6.58%. CUPRUM 35.36, and HAFNIUM 36.56%, is it appropriate to use it as AURUM?

Hope some ‘nanoparticles specialists’ would explain.

If you look into these two slides carefully, you will get a lot of things to laugh at!!

If AUR MET 6C contains AUR 2.82% and CUPRUM 75.82%, which will be the active principles? CUPRUM or AURUM?

If AUR 200 contains AURUM 12.14%, POTTASSIUM 29.36%, CUPRUM 25.8%, and SODIUM 20.08%, how can you say AURUM NANOPARTICLES are the active principles of Aur Met 200?

If AUR MET 50M contains AURUM 9.73% , CUPRUM 53.27%, and COBALT 23%, how can you say it is AURUM MET? Rather callit and use it as CUPRUM MET?

If AURUM MET CM contains AURUM 6.58%. CUPRUM 35.36, and HAFNIUM 36.56%, is it appropriate to use it as AURUM?

Remember, they have published these works in “peer reviewed journals”, and a lay man like me should not question it!

Peer-reviewed nonsense! Who are those peers?

Any research paper has TWO aspects. One is related with the the methods used in research and second is the interpretations and conclusions. Peer reviewers consider the first part only to recommend publication. They never verify whether the interpretations and conclusions are correct. If methods and format is according to standards, they will accept it for publication. That is why we say a lot of research works published, with nonsense interpretations and conclusions.

If you have a brain, use it to decide what is right and what is wrong. Do not accept anything as truth, only because there is a “peer reviewed paper” published about it. Do not close your mind towards a new idea only because there no a “published paper”. If you use your brain, you will realize that there are a lot of “peer reviewed papers” which make utter nonsense theories. About homeopathy also. Like nanoparticles theory.


Responding to my proposition that MICROCRYSTALLINE CELLULOSE could be a superior substitute to LACTOSE and CANE SUGAR as dispensing vehicles for potentized homeopathic drugs, many friends asked me to provide more details regarding the safety studies of MCCP. Hence I am posting here World Health Organization Report on Microcrystalline Cellulose, prepared by the forty-ninth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA), World Health Organization, Geneva 1998. First draft prepared  by Dr J.B. Greig, Department of Health, Skipton House, 80 London Road, London, SE1 6LW, UK

This report contains a detailed overview, evaluation and comments upon hundreds of studies done regarding Biochemical aspects (Absorption, distribution and excretion), Acute toxicity of microcrystalline cellulose in animals, Short-term toxicity studies, Long-term toxicity/carcinogenicity studies, Reproductive toxicity studies, Special studies on embryotoxicity and teratogenicity, Special studies on genotoxicity, Special studies on sensitization, Special studies on skin and eye irritation, Special studies on effects of cellulose fibre on tumour growth,  Toxicity consequent to substance abuse,  Changes in gastrointestinal function and nutrient balance etc with complete references.

“The Committee concluded that the toxicological data from humans  and animals provided no evidence that the ingestion of  microcrystalline cellulose can cause toxic effects in humans when used  in foods according to good manufacturing practice”.

The committee concludes the report with the following statement:

“Persorption of microcrystalline cellulose was reported in various species, which included rats, in early studies. A recent study in which a special fine particle size preparation of microcrystalline  cellulose (median diameter of particles 6 µm) was administered orally to rats (5 g/kg bw per day) for 90 days has failed to confirm the earlier observations. In this study precautions were taken to ensure that, at autopsy, there was no cross-contamination of the tissues with fine particulate matter.

In various parenteral studies of the acute toxicity of microcrystalline cellulose in animals there have been signs consistent with a tissue response to foreign particles. Similarly, microcrystalline cellulose has been associated with the formation of granulomas in human lung when it has been injected intravenously during drug abuse. No such lesions have been described as a consequence of oral ingestion of microcrystalline cellulose by rats or humans.

In 90-day toxicity tests during which microcrystalline cellulose was administered to rats in the diet at concentrations of 2.5 to 50%, increased consumption of food to compensate for the content of this material was observed. Although this may have some effects on mineral absorption there was, in general, no compound-related systemic toxicity. The NOEL exceeded 50 g/kg diet, at which dose level the mean intakes of microcrystalline cellulose by male and female rats were 3.8 and 4.4 g/kg bw per day, respectively.

A two-year feeding study of microcrystalline cellulose in rats was brought to the attention of the Committee. Despite a lack of evidence of toxic effects, the Committee considered that the execution and reporting of the study were not adequate to identify a NOEL.

In vitro and  in vivo genotoxicity studies were negative.

In a three-generation reproductive toxicity study in rats that had been reviewed by an earlier Committee, there were some effects of using 30% microcrystalline cellulose in the diet; these had been considered to be a consequence of the quantity of material reducing the energy density of the diet. However, in recent embryotoxicity and teratogenicity studies in rats there was no evidence of compound-related effects at dietary levels up to 50 g of microcrystalline cellulose per kg diet (equal to 4.6 g/kg bw per day), given on days 6 to 15 of pregnancy.

In some human studies there have been reports of alterations to gastrointestinal function following ingestion of microcrystalline cellulose. The changes do not appear to be related to systemic toxicity”

Microcrystalline cellulose is a purified, partially depolymerzed cellulose prepared by treating alpha-cellulose, obtained as a pulp from fibrous plant material, with mineral acids. The degree of polymerization is typically less than 400. Not more than 10% of the material has a particle size of less than 5 nanometer. Insoluble in water, ethanol, ether and dilute mineral acids. Slightly soluble in sodium hydroxide solution.

Microcrystalline cellulose (C6H10O5)n is refined wood pulp. It is a white, free-flowing powder. Chemically, it is an inert substance, is not degraded during digestion and has no appreciable absorption. In large quantities it provides dietary bulk and may lead to a laxative effect.

Microcrystalline cellulose is a commonly used excipient in the pharmaceutical industry. It has excellent compressibility properties and is used in solid dose forms, such as tablets. Tablets can be formed that are hard, but dissolve quickly. Microcrystalline cellulose is the same as cellulose, except that it meets USP standards.

It is also found in many processed food products, and may be used as an anti-caking agent, stabilizer, texture modifier, or suspending agent among other uses. According to the Select Committee on GRAS Substances, microcrystalline cellulose is generally regarded as safe when used in normal quantities.

The most common form is used in vitamin supplements or tablets. It is also used in plaque assays for counting viruses, as an alternative to carboxymethylcellulose.

A naturally occurring polymer, it is composed of glucose units connected by a 1-4 beta glycosidic bond. These linear cellulose chains are bundled together as microfibril spiralled together in the walls of plant cell. Each microfibril exhibits a high degree of three-dimensional internal bonding resulting in a crystalline structure that is insoluble in water and resistant to reagents. There are, however, relatively weak segments of the microfibril with weaker internal bonding. These are called amorphous regions; some argue that they are more accurately called dislocations, because of the single-phase structure of microfibrils. The crystalline region is isolated to produce microcrystalline cellulose.

Approved within the European Union as a thickener, stabilizer or emulsifiers microcrystalline cellulose was granted the E number E460(i) with basic cellulose given the number E460.

Microcrystalline cellulose (MCC) is pure partially depolymerized cellulose synthesized from α-cellulose precursor. The MCC can be synthesized by different processes such as reactive extrusion, enzyme mediated, steam explosion and acid hydrolysis. The later process can be done using mineral acids such as H2SO4, HCl and HBr as well as ionic liquids. The role of these reagents is to destroy the amorphous regions remaining the crystalline domains. The degree of polymerization is typically less than 400. The MCC particles with size lower than 5 µm must not be more than 10%. The MCC is a valuable additive in pharmaceutical, food, cosmetic and other industries. Different properties of MCC are measured to qualify its suitability to such utilization, namely particle size, density, compressibility index, angle of repose, powder porosity, hydration swelling capacity, moisture sorption capacity, moisture content, crystallinity index, crystallite size and mechanical properties such as hardness and tensile strength. Thermogravimetric analysis (TGA) and differential thermal analysis (DTA) or differential scanning calorimetry (DSC) are also important to predict the thermal behavior of the MCC upon heat stresses.

Microcrystalline cellulose is a widely used excipient, an inert substance used in many pill and tablet formulations. As an insoluble fiber, microcrystalline cellulose is not absorbed into the blood stream, so it cannot cause toxicity when taken orally. In fact, it is so inert it is often used as a placebo in controlled drug studies. However, some side effects have been noted in animal studies, although usually at much higher dosages than would be normal for a human subject.

World Health Organization Report on Microcrystalline Cellulose

INTERNATIONAL PROGRAMME ON CHEMICAL SAFETY WORLD HEALTH ORGANIZATION- SAFETY EVALUATION OF CERTAIN FOOD ADDITIVES AND CONTAMINANTS – WHO FOOD ADDITIVES SERIES 40-  Prepared by: The forty-ninth meeting of the Joint FAO/WHO Expert Committee on Food Additives (JECFA).  World Health Organization, Geneva 1998 –  First draft prepared     by Dr J.B. Greig Department of Health, Skipton House, 80 London Road, London, SE1 6LW, UK


Microcrystalline cellulose was evaluated at the fifteenth, seventeenth and nineteenth meetings of the Committee (see Annex 1, references 26, 32 and 38). At the nineteenth meeting an ADI “not specified” was allocated. In the light of concern about possible persorption and consequential adverse effects of fine particles, the substance was re-evaluated at the present meeting.


Biochemical aspects-  Absorption, distribution and excretion


Four rats were fed 14C-labelled microcrystalline cellulose at 10 or 20% of their diet. No evidence of degradation or digestion was noted. Faecal recoveries of radioactivity ranged from 96-104% and were complete for all labelled material. No radioactivity appeared in the urine (Baker, 1966).

A study was specifically designed to investigate the possibility that persorption of microcrystalline cellulose might induce toxicological effects. Groups of male and female Sprague-Dawley CD rats (20 per group) from Charles River Laboratories were administered, by gavage, suspensions of a special fine particle-size microcrystalline cellulose (median particle size 6 µm). The rats were dosed orally daily for 90 consecutive days at a level of 5000 mg/kg bw per day by means of a 25% suspension in tap water. The animals were killed on study days 91-94 and necropsies were carried out under conditions that reduced the possibility of contamination of tissues with fine particulates. The birefringent microcrystalline cellulose particles were not detected in any organ or tissue, including gut-associated lymphoid tissue, liver, lung, spleen and brain. The size limit for detection of the particles was considered to be < 1 µm (Kotkoskie  et al., 1996; FMC Corporation N.V., 1996


One human subject received 150 g of microcrystalline cellulose daily in two portions for a 15-day adaptation period. He then received 14C-labelled microcrystalline cellulose (47.6 µCi) in two portions on one day. Supplementation of the diet with unlabelled microcrystalline cellulose continued for 10 days. Twenty-four-hour faecal and urine collections were examined for radioactivity. No radioactivity appeared in the urine or in the expired CO2. All administered radioactivity (98.9 ± 3.0%) was recovered from the faeces within two days (Baker, 1968).

Metabolism of a preparation of 14C-labelled cellulose by four volunteers has been shown to be increased by the consumption, for a period of 3 months, of an additional 7 g/per day of dietary fibre. In six subjects with an ileostomy, the cumulative excretion of 14CO2 was lower than in controls. In two constipated subjects metabolism appeared to be more extensive and occurred over a longer period (Walters  et al., 1989).

Examination of the stools of one male and one female patient given 30 g microcrystalline cellulose as dry flour or gel for 5´ weeks showed the presence of undegraded material of the same birefringence as the original microcrystalline cellulose administered. No significant effects on the human gastrointestinal tract were noted during the administration (Tusing  et al., 1964).

Most (87%) of the radiolabel associated with 131I-labelled alpha-cellulose fibres (retained by a sieve with pores of 1 mm diam) was excreted by 4 male and 4 female volunteers within 5 days of ingestion. Less than 2% of the faecal radiolabel was unbound; urinary excretion of unbound radio-iodine accounted for another 1.9% of the total dose (Carryer  et al., 1982).

Other studies have been carried out to demonstrate the relationship between persorbability and size and consistency of granules. Using quartz sand, the upper limit for persorbability was shown to be 150 µm. Starch granules must be structurally largely intact to possess the property of persorbability. Persorbed starch granules may be eliminated in the urine, pulmonary alveoli, peritoneal cavity, cerebrospinal fluid, via lactating milk and transplacentally (Volkheimer  et al., 1968).

In another study, dyed plant foods (oatmeal, creamed corn) were fed to human subjects, and blood and urine were examined for coloured fibres. Dyed fibres were shown to be present (Schreiber, 1974).

Lycopodium spores and pollen grains have also been shown to be persorbed by humans (Linskens & Jorde, 1974).

Mean intake of dietary microcrystalline cellulose in the USA has been estimated to range from 2.7 g/person per day (children 2 years of age) to 5.1 g/person per day (young adult males). For heavy consumer intake of microcrystalline cellulose (90th percentile) the values are 5.4 to 10.2 g/person per day for the same age groups (CanTox Inc., 1993).

The mean intake of dietary microcrystalline cellulose in the United Kingdom has been estimated as 0.65 g/person per day. The highest mean intake, 0.90 g/person per day, was for children aged 10-11 (the youngest group for which data were available). For heavy consumer intake of microcrystalline cellulose (90th percentile) the values ranged from 1.13 g/person per day for adults age 16-24 to 1.83 g/person per day for males age 10-11 (Egan & Heimbach, 1994).

Persorption in animal species:

Rats, pigs and dogs were used to study the persorption of microcrystalline cellulose. The animals were not fed for 12 hours prior to oral administration of the test compound. Rats, dogs and pigs were given 0.5, 140 and 200 g, respectively, of the test compound. Venous blood was taken from the animals 1-2 hours after administration of the test compound, and examined for particles. Persorbed particles were demonstrated in the blood of all three species. The average maximum diameter for persorbed particles was greater in rats than in dogs or pigs (Pahlke & Friedrich, 1974)

Acute toxicity of microcrystalline cellulose in animals

No deaths in 10 rats of each sex administered 5000 mg/kg of Avicel RCN-15.

No deaths in 5 rats of each sex administered 5000 mg/kg of Avicel AC-815.

No deaths in 5 rats of each sex treated with 2000 mg/kg of Avicel RCN-15.

No deaths in 5 rats of each sex treated with 2000 mg/kg of Avicel AC-815.

No deaths in 5 rats of each sex exposed to 5.35 mg/litre of Avicel AC-815.

In the studies summarized in Table 1, there was no evidence of toxicity of microcrystalline cellulose preparations administered either orally or dermally to rats at doses of 5000 or 2000 mg/kg bw, respectively. The observations seen at necropsy in animals treated  intraperitoneally with Cellan 300 at 3160 mg/kg bw are consistent with an irritant reaction caused by the presence of foreign material. An inhalation toxicity study showed only transient effects at a concentration of 5.35 mg/litre.

Groups of five male Sprague-Dawley rats received a single oral dose, by stomach tube, of 10.0, 31.6, 100, 316, 1000 or 3160 mg/kg bw of a suspension of Cellan 300 (refined alpha-cellulose) in either  distilled water or Mazola corn oil. The animals were observed for 7 days following administration. No differences were observed among the groups as regards the average body weight, appearance and behavior  compared to untreated rats. No observable gross pathology was revealed  at autopsy in animals dosed with either suspension. Therefore, the  acute oral LD50 was >3160 mg/kg (Pallotta, 1959).

Similar single doses of refined alpha-cellulose were given i.p. in distilled water suspension to five male rats. During 7 days observation there were no abnormalities in the rats given 316 mg/kg bw or less. At 1000 and 3160 mg/kg bw inactivity, laboured respiration and ataxia were observed 10 min after administration and, at 3160 mg/kg bw, ptosis and sprawling of the limbs were observed. These  animals appeared normal after 24 hours and for the remainder of the  observation period. At sacrifice body weights were higher than normal and gross autopsy revealed adhesions between the liver, diaphragm and peritoneal wall and congestion of the kidneys. Masses resembling   unabsorbed compound were also observed and these were found to a small extent in the mesentery of the animals administered 316 mg/kg bw.

There were no deaths and therefore the acute i.p. LD50 was >3160 mg/kg bw (Pallotta, 1959).

Ten male and ten female Sprague-Dawley rats fasted overnight were  fed Avicel RCN-15 (a mixture of 85% microcrystalline cellulose with 15% guar gum) at a dose level of 5000 mg/kg bw mixed with parmesan cheese. Six of ten males and five of ten females consumed the mixture within 24 hours. After a 14-day period during which all rats gained  weight normally they were killed. There were no gross lesions at necropsy. Under the specified conditions of administration the LD50 was >5000 mg/kg bw (Freeman, 1991a).

An acute inhalation toxicity study using a preparation of Avicel AC-815 (composed of 85% microcrystalline cellulose and 15% calcium  alginate) with mass median aerodynamic diameter of 8.48-8.61 µm (range of measures) was dispersed and delivered at a mean concentration of  5.35 mg/litre in a nose-only inhalation exposure chamber to 5 male and 5 female Crl:CDBR VAF Plus rats for a period of 4 hours. The rats were observed over the 14 days after removal from the chamber. The only signs of toxicity were on removal from the chamber and consisted of  chromodacryorrhea, chromorhinorrhea and, in one male rat, decreased  locomotion; these signs had resolved by the next day. After 14 days no gross lesions were observed at necropsy (Signorin, 1996)

Short-term toxicity studies


Groups of four male rats were kept on diets containing 0.25, 2.5 or 25% of various edible celluloses for 3 months. No differences were observed among the groups with regard to growth and faecal output. Histopathology of the gastrointestinal tract revealed no treatment-related abnormalities (Frey  et al., 1928).

Three groups of five male rats received 0.5 or 10% microcrystalline cellulose in their diet for 8 weeks. Growth was comparable to controls but the 10% group showed slightly lower body  weights. Haematology, serum chemistry and vitamin B1 levels in blood and faeces showed no differences from controls (Asahi Chemical Industry Co., 1966).

Groups of five male weanling Sprague-Dawley rats received 0, 5, 10 or 20% of acid-washed cellulose in their diet during three consecutive nutrient balance trials over a period of 17 days. Absorption of magnesium and zinc were significantly lower in the animals that were receiving the 10 and 20% cellulose diets. Histopathology of the gastrointestinal tract revealed increased mitotic activity and the presence of increased numbers of neutrophils in crypt epithelial cells, particularly of the duodenum and jejunum (Gordon  et al., 1983).

A mixture of four types of Elceme (in the ratio of 1:1:1:1) was fed to groups of Wistar rats for 30 days at a dietary level of 50%,  and for 90 days at a dietary level of 10% (Elceme is a  microcrystalline cellulose, and the four types are identified by particle size, namely, 1-50 (powder), 1-100 (powder), 1-150 (fibrillar), 90-250 (granulate)). All test animals were observed for food intake and weight gain. For animals in the 10% group, urinalysis,  haematological tests and serum biochemical tests were carried out at weeks 6 and 13 of the test. A complete autopsy including  histopathology was carried out at the end of the study. Animals in the 50% group were subjected to a persorption test, on the last day of the  study, by addition of a cellulose staining dye (Renal, Wine-red) to  the food of the test animals at a level equivalent to 5% of the Elceme. The animals were sacrificed 24 hours after administration of the diet, and a careful histological examination was made of the gastrointestinal tract, spleen, liver, kidney and heart for stained particles.

Animals in the 10% group gained significantly less weight than  those in the control group; the marked decrease commenced in the third or fourth week of the study. Food intake was similar in test and  control groups. Urinalysis, haematological values and biochemical values were similar for test and control group 1. At autopsy some ofthe rats on the test diet had distended stomachs, which often contained considerable amounts of the test diet. The absolute liver and kidney weights and the ratio of the weight of these organs to brain weight was increased in test animals when compared with control animals. No compound-related pathology was reported. Animals in the 50% group showed considerable less weight gain than control animals in spite of a marked increase in food consumption. No persorption of dyed fibres was observed (Ferch, 1973a,b).

Randomly bred rats of both sexes were divided into groups that  received a control diet or the control diet with 330 mg/kg microcrystalline cellulose for a period of 6 months. Six rats in each group were then killed, their organs were examined, and tissues were taken for histopathology. No effects of the treatment were observed (Yartsev  et al., 1989).

Groups of Crl: CD(R) BR/VAF/Plus rats (20/sex per group) were administered 0 (control), 25 000 or 50 000 mg/kg Avicel RCN-15 in the diet for 90 days. A few test animals were noted as having  chromodacryorrhea/ chromorhinorrhea, but this was not considered to be   biologically significant. In some early weeks the rats increased diet consumption, probably to allow for the increased dietary fibre content. Body weight gain was unaffected. During the study and at necropsy there was no evidence of treatment-related changes. Clinical chemistry, haematology and organ weights were unaffected by treatment. Histopathology of 34 organs or tissues, including gastrointestinal tract and gut-associated lymphoid tissue of the ileum, provided no evidence of toxicity of microcrystalline cellulose. The calculated  daily consumption of microcrystalline cellulose was 3769 mg/kg bw per day for males and 4446 mg/kg bw per day for females. The author noted that the NOEL exceeded 50 000 mg/kg diet (Freeman, 1992a).

Groups of Sprague-Dawley CD rats (20 rats/dose per sex) from Charles River Laboratories were administered 0 (control), 25 000 or 50000 mg/kg Avicel CL-611 in the diet for 90 days. (Avicel CL-611 orAvicel(R) Cellulose Gel is composed of 85% microcrystalline cellulose and 15% sodium carboxymethyl cellulose). There were no differences in weight gain of the males; a body weight gain decrement in females was attributed to a decreased caloric intake. No adverse  effects attributable to the treatment were observed. At necropsy organ  weights of the test groups were normal other than changes to adrenals of males receiving 50 000 mg/kg and to absolute brain and kidney weights in females receiving 25 000 mg/kg, but these were not  attributed to the treatment. Histopathology of 36 organs or tissues  from the control and high-dose groups, including gastrointestinal tract and gut-associated lymphoid tissue of the ileum, provided no evidence of toxicity of the microcrystalline cellulose. The mean  nominal consumptions, averaged over weekly periods, of Avicel CL-611  by males and females of the top-dose groups ranged from 2768 to 5577 and 3673 to 6045 mg/kg bw per day, respectively (Freeman, 1994a).

Microcrystalline cellulose (Avicel) was used as a positive control  in a short-term toxicity study (approximately 13 weeks) of Cellulon, a  cellulose fibre. Sprague-Dawley Crl:CB (SD) BR rats, 20 rats/sex per group, received a diet containing 0, 5 or 10% of the appropriate fibre ad libitum. Animals were checked daily, and body weights and food consumption were monitored weekly. Haematology (10 parameters) and clinical chemistry (14 parameters) were performed on blood samples taken from 10 rats/sex per group. All animals were necropsied, and gross observations and the weights of liver, testes with epididymes, adrenals and kidneys were recorded. Histological examination was  carried out on tissue sections from control and high-dose groups.

Food consumption was increased in the groups fed cellulose fibre, although there were no differences in body weight between the fibre-fed and control groups. This effect was attributed to the altered nutritional value of the diet. From the haematology and  clinical chemistry there was only one significant difference of   microcrystalline cellulose group from the control value; this was in  the group of female rats fed 5% microcrystalline cellulose in which there was an elevation of the haematocrit. There was no evidence of a  dose response.

Study of the necropsy results and the histological observations  indicate that there was no evidence of any treatment-related effects of microcrystalline cellulose during the 13-week feeding study in rats  at either 5 or 10% in the diet (Schmitt  et al., 1991).

Groups of Sprague-Dawley (CD) rats (20 rats/dose per sex) from Charles River Laboratories were administered, by gavage, suspensions  of a special, fine particle size, microcrystalline cellulose (median particle size 6 µm). The dose levels were 0 (control), 500, 2500 or  5000 mg/kg per day as a 25% suspension in tap water. Dosing was   performed daily for 90 consecutive days. No treatment-related deaths occurred during the study and the only treatment-related clinical sign (pale faeces) was not attributed to toxicity. There were no toxicologically significant effects in treated animals with respect to body weight, absolute and relative organ weights (5 organs weighed), food consumption, clinical chemistry measurements, haematology measurements or opthalmoscopic examinations. In animals that has received 5000 mg/kg per day there were no treatment-related lesions detected histopathologically (in 36 tissues including gut-associated lymphoid tissue, liver, lung, spleen and brain) nor was there any macroscopic or microscopic finding of microemboli or granulomatous  inflammatory lesions (Kotkoskie  et al., 1996).

Long-term toxicity/carcinogenicity studies


Three groups of 50 male and 50 female rats received in their die  for 72 weeks either 30% ordinary cellulose or dry microcrystalline cellulose or micro-crystalline cellulose gel. Appearance and behavior was comparable in all groups. No adverse effects were noted. The body weights of males given microcrystalline cellulose gel were higher than  those of the controls. Food efficiency, survival and haematology were comparable in all groups. The liver and kidney weights of males receiving microcrystalline cellulose gel were higher than the controls. Gross and histopathology showed some dystrophic calcification of renal tubules in females on microcrystalline  cellulose but all other organs appeared unremarkable. Tumour incidence  did not differ between the groups (Hazleton Labs, 1963).

The Committtee was aware of a study in which a microcrystalline  cellulose preparation, of which 90% of the particles had a diameter   < 20 µm, was fed to male and female rats at 0 (control), 30, 100 or 200 g/kg diet. The high mortality during the course of the study, the evidence of confounding infection, the limited number of animals for which there was histopathological examination, and the absence of details of the first year of feeding do not provide adequate reassurance as to the ability of this study to detect other than gross effects (Lewerenz  et al., 1981).

Reproductive toxicity studies


Groups of eight male and 16 female rats were used to produce P,  F1a, F1b, F2 and F3 generations after having been fed on diets containing 30% microcrystalline cellulose flour or gel or ordinary cellulose as a control. The presence in the diet of such an amount of  non-nutritious material, which contributed no calories, had an adverse effect on reproduction. Fertility and numbers of live pups were  relatively depressed, and lactation performances in all three  generations, as well as survival and the physical condition of the pups, were unsatisfactory throughout the study. The new-born pup appeared smaller, weak and showed evidence of disturbed motor  coordination. Liver weights were increased in the group receiving microcrystalline cellulose gel in all generations but other organ  weights showed no consistent patterns. At autopsy female rats of all generations showed kidney changes comprising pitting, occasional  enlargement and zonation of the cortex. Other organs showed  no consistent changes. No teratological deformities were seen (Hazleton Labs, 1964).

Special studies on embryotoxicity and teratogenicity


Seventy-two rats (Sprague-Dawley CD) divided into eight groups were fed a mixture of four types of Elceme in the ratio of 1:1:1:1 in the diet at a level of 0, 2.5, 5 or 10% for 10 days, between days 6 and 15 of pregnancy. Rats of four test groups were killed on day 21 of pregnancy and the following parameters studied: number of fetuses and resorption sites, litter size and average weight of rats, average weight of fetuses and average backbone length. Fetuses were also examined for soft tissue or skeletal defects. The remaining groups were allowed to bear young, which were maintained to weaning (21 days). The following parameters were studied: litter size, weight of  pups at days 7 and 21, and there was a histological study of the offspring. Although there is some suggestion that administration of dietary Elceme resulted in a dose-dependent increase in resorption  sites, as well as a change in sex ratio, and possible defects such as  opaque crystalline lenses, the data has not been presented in a manner  that permits a meaningful interpretation. However, the author concluded that Elceme is non-teratogenic (Ferch, 1973a,b).

Groups of 25 presumed pregnant Crl:CD(R) BR VAF/Plus rats were administered 0 (control), 25 000 or 50 000 mg Avicel RCN-15/kg diet (equal to 2.1 and 4.5 g/kg bw per day, respectively)  ad libitum on   days 6 to 15 of gestation. Animals received basal diet at all other  times. In the group receiving 50 000 mg/kg the food consumption on  days 6 to 15 was significantly higher than that of controls, probably because of the increased fibre content. On day 20 of gestation thedams were killed by carbon dioxide inhalation and the following parameters studied: number and distribution of implantation sites,  early and late resorptions, live and dead fetuses and corpora lutea.  External, visceral and skeletal examinations of the fetuses were also  performed. There was no evidence of any adverse effects of the test  material on either the dams or the fetuses. Due to a protocol error fetal sex was not recorded (Freeman, 1992b).

Groups of 25 presumed pregnant Charles River Sprague-Dawley CD  rats were administered 0 (control), 25 000 or 50 000 mg Avicel  CL-611/kg (equal to 2.2 and 4.6 g/kg bw per day, respectively) diet   ad libitum on days 6 to 15 of gestation. Animals received basal diet at all other times. In the test groups the food consumption on days     to 15 was significantly higher than for controls, probably because of   the increased fibre content. The parameters studied and examinations performed were the same as in the study of Freeman (1992b). There was  no evidence of any effects of the Avicel treatment on the fetuses, and there was no evidence of a change of sex ratio in the pups or of eye defects. Under the conditions of the study, the maternal and fetal  NOEL was > 50 000 mg/kg diet (equal to 4.6 g/kg bw per day) (Freeman,   1994b).

Special studies on genotoxicity

Various microcrystalline cellulose preparations have been tested for genotoxicity in several different assay systems. The results of which were negative, are summarized in Table 2.

In the reverse mutation assays the microcrystalline cellulose formulations produced a heavy precipitate on the plate at the highest concentration. Solubility also affected the forward mutation assays and it was not possible to include concentrations of the test material that were cytotoxic. In the  in vivo mammalian micronucleus assays it is improbable that there was appreciable persorption of the test materials, and, therefore, there was little exposure of the bone marrow cells. In the test in which Avicel RCN-15 was used it was administered admixed with the diet of male and female ICR mice. Only mice that had consumed all the diet within 10 hours were retained in the study and were killed after 24, 48 or 72 hours. Because one group of control mice had 0 micronuclei per 1000 polychromatic erythrocytes, the comparison with the test group was statistically significant. This was not considered to be a valid observation. There is no evidence that microcrystalline cellulose is genotoxic.

Special studies on sensitization

  Avicel RCN-15 was determined to be non-sensitizing when topically  applied to ten male and ten female Hartley guinea-pigs (Freeman,  1991e).

Avicel AC-815 was determined to be non-sensitizing when topicall    applied to ten male Hartley guinea-pigs (Freeman, 1996c).

Special studies on skin and eye irritation

Avicel RCN-15 was judged to be minimally irritating after  instillation into the eyes of four male and two female New Zealand White rabbits (Freeman, 1991c).

Avicel AC-815 was judged to be minimally irritating after   instillation into the eyes of four male and two female New Zealand  White rabbits (Freeman, 1996a).

Avicel RCN-15 was judged to be non-irritating after a 4-hour occlusive contact with the skin of three male and three female New Zealand White rabbits (Freeman, 1991d).

Avicel AC-815 was judged to be non-irritating after a 4-hour occlusive contact with the skin of three male and three female New Zealand White rabbits (Freeman, 1996b).

Special studies on effects of cellulose fibre on tumour growth 

The effect of artifical diets containing varied concentrations of either wheat bran or pure cellulose fibre on the induction of mammary  tumours by  N-nitrosomethylurea (i.v., 40 mg/kg) was studied in female F344 rats. The wheat bran diet appeared to possess anti-promotion properties that pure cellulose lacked. The concentrations of serum estrogens, urinary estrogens and faecal estrogens did not vary in a consistent, statistically significant manner (Cohen  et al., 1996).

The effect of a high-fibre diet containing 45 000 mg/kg Avicel PH- 105 on the development of colon tumours was investigated in male Wistar rats that were injected with 1,2-dimethylhydrazine dihydrochloride (25 mg/kg, s.c., once weekly for 16 weeks). The test and control diets were administered for 2 weeks prior to the first injection of the carcinogen. There was a reduction in the number of animals bearing colon tumours and a statistically significant reduction in the number of colon tumours/rat in the high-fibre dietary group. However, for small bowel tumours and tumours of the ear canal there was no significant difference between the dietary groups Freeman et al., 1978).

A later study by the same authors demonstrated that there was no significant effect of increasing the level of cellulose in the diet to 9000 mg/kg (Freeman  et al., 1980).

Observations in humans

Toxicity consequent to substance abuse 

Intravenous abuse of drugs available in tablet form has led to the detection of excipients, e.g., talc, magnesium stearate or microcrystalline cellulose, in the tissues of a series of 33 fatality cases of intravenous drug addicts. Microcrystalline cellulose (21  cases) and talc (31 cases) were detected most frequently and, in some cases, were associated with granulomatous lesions (Kringsholm & Christoffersen, 1987).

Changes in gastrointestinal function and nutrient balance

A number of clinical studies using refined cellulose as roughage  in the human diet for the treatment of constipation showed no  deleterious effects. Groups of 18 children received regular amounts of   edible cellulose instead of normal cereal for three months. The only  effect noted was an increase in bowel movements but no diarrhoea or other gastrointestinal disturbances were seen (Frey  et al., 1928).

Eight male and eight female volunteers supplemented their normal diet with 30 g microcrystalline cellulose per day as either dry powder or gel (15% aqueous) for 6 weeks followed by 2 weeks without supplementation. No adverse findings were reported regarding acceptance or body weight but most subjects complained of fullness and mild constipation. Haematology was normal in all subjects. Biochemical blood values showed no differences between treatment and control periods, nor was there evidence of liver or kidney function disturbance. Urinalysis produced normal findings. The faecal flora remained unchanged. The cellulose content of faeces increase five to eight times during the test period. Microscopy revealed the presence of microcrystalline cellulose (Hazleton Labs, 1962).

In another study, eight healthy males received 30 g microcrystalline cellulose daily as supplement to their diet for 15 days. D-xylose absorption varied between pretest, test and post-test periods, being lower during microcrystalline cellulose ingestion. The absorption of 131I-triolein was unaffected by microcrystalline  cellulose ingestion. No change was noted in the faecal flora nor was there any significant effect on blood chemistry during ingestion of microcrystalline cellulose. Examination of urine, blood and faecal levels of vitamin B1 during microcrystalline cellulose ingestion showed no difference from control periods (Asahi Chemical Industry Co., 1966).

Twelve men consumed diets containing fibres from various sources for periods of 4 weeks. There was no significant difference between alues of serum cholesterol, triglyceride and free fatty acid levels measured after consumption of the basal diet, compared with the values measured after consumption of a diet containing cellulose fibres (90% cellulose, 10% hemicellulose; James River Corp., Berlin, New Hampshire, USA). There were no significant differences in plasma VLDL and HDL cholesterol or in the ratio of HDL/VLDL+LDL cholesterol. However, the increase in plasma LDL cholesterol after the cellulose diet was significant (Behall  et al., 1984).

A similar study in a group of four men and six women could detect no effect of a diet containing added alpha-cellulose (15 g daily) on serum total cholesterol, triglycerides, HDL cholesterol and the ratio of HDL to total cholesterol. The cellulose was well tolerated (Hillman et al., 1985).

A double-blind cross-over trial of the effects of guar gum andmicrocrystalline cellulose on metabolic control and serum lipids in 22 Type 2 diabetic patients has been carried out. The fibre preparations were given at 15 g/day for a 2-week period and then at 5 g/day for the remaining 10-week period of each treatment phase. There was no effect of the microcrystalline cellulose diet on fasting blood glucose level, glycosylated haemoglobin, serum HDL-cholesterol, serum triglycerides, serum zinc or ferritin, or urinary magnesium excretion (Niemi   et al., 1988).

The effect of various dietary fibres, including microcrystalline cellulose (40 g), on the uptake of vitamin A (approximately sixty times the daily requirement) from a test meal was investigated in 11 female subjects aged 19 to 22. All the dietary fibres significantly increased the absorption of the vitamin A over a period of 9 hours (Kasper  et al., 1979).

A study of apparent mineral balance in a group of eleven men revealed that there was no significant effect of cellulose, added to the diet at 7.5 g per 1000 kcal for 4 weeks, on the mineral balance of calcium, magnesium, manganese, iron, copper or zinc. However, in this report the source of the cellulose fibre was not specified (Behall et al., 1987).

The addition of nutritional grade cellulose (21 g) to the daily diet of healthy adolescent girls resulted in reduction of the serum calcium, phosphorus and iron concentrations. The authors suggested that high-fibre diets may not be advisable (Godara  et al., 1981).

A study of only three men on a low-fibre diet claimed changes in mineral balance consequent on the consumption of additional cellulose fibre, 10 g of Whatman No. 3 filter paper daily, in the diet (Ismail-Beigi  et al., 1977).

Microcrystalline cellulose (5 g) did not appear to inhibit the uptake of iron in women who were neither pregnant nor lactating (Gillooly  et al., 1984).

A group of twenty women, aged 27-48, who were given 20 g packs of alpha-cellulose to be consumed daily for three months, were included in a study of the effect of indole-3-carbinol on estrogen metabolite ratios. Because the control group and the group fed indole-3-carbinol received capsules, the cellulose group could not be blinded; in addition, an unspecified number of subjects in this group dropped out as they found that the cellulose suspension was unpalatable. However, the authors suggest that the estrogen metabolite ratio in the high- fibre group was not different from that in the control group (Bradlow et al., 1994).


Persorption of microcrystalline cellulose was reported in various species, which included rats, in early studies. A recent study in which a special fine particle size preparation of microcrystalline  cellulose (median diameter of particles 6 µm) was administered orally to rats (5 g/kg bw per day) for 90 days has failed to confirm the earlier observations. In this study precautions were taken to ensure that, at autopsy, there was no cross-contamination of the tissues with fine particulate matter.

In various parenteral studies of the acute toxicity of microcrystalline cellulose in animals there have been signs consistent with a tissue response to foreign particles. Similarly, microcrystalline cellulose has been associated with the formation of granulomas in human lung when it has been injected intravenously during drug abuse. No such lesions have been described as a consequence of oral ingestion of microcrystalline cellulose by rats or humans.

In 90-day toxicity tests during which microcrystalline cellulose was administered to rats in the diet at concentrations of 2.5 to 50%, increased consumption of food to compensate for the content of this material was observed. Although this may have some effects on mineral absorption there was, in general, no compound-related systemic toxicity. The NOEL exceeded 50 g/kg diet, at which dose level the mean intakes of microcrystalline cellulose by male and female rats were 3.8 and 4.4 g/kg bw per day, respectively.

A two-year feeding study of microcrystalline cellulose in rats was brought to the attention of the Committee. Despite a lack of evidence of toxic effects, the Committee considered that the execution and reporting of the study were not adequate to identify a NOEL.

In vitro and  in vivo genotoxicity studies were negative.

In a three-generation reproductive toxicity study in rats that had been reviewed by an earlier Committee, there were some effects of using 30% microcrystalline cellulose in the diet; these had been considered to be a consequence of the quantity of material reducing the energy density of the diet. However, in recent embryotoxicity and teratogenicity studies in rats there was no evidence of compound-related effects at dietary levels up to 50 g of microcrystalline cellulose per kg diet (equal to 4.6 g/kg bw per day), given on days 6 to 15 of pregnancy.

In some human studies there have been reports of alterations to gastrointestinal function following ingestion of microcrystalline cellulose. The changes do not appear to be related to systemic toxicity.


The Committee concluded that the toxicological data from humans  and animals provided no evidence that the ingestion of  microcrystalline cellulose can cause toxic effects in humans when used  in foods according to good manufacturing practice.

It is recognized that small particles of other materials may be   persorbed and that the extent of persorption is greater with sub-micrometre particles. Despite the absence of any demonstrated persorption of microcrystalline cellulose in the recent study in rats, the Committee, as a precautionary measure, revised the specifications   for microcrystalline cellulose at the present meeting to limit the content of particles less than 5 µm in diameter. The Committee  retained the ADI “not specified” for microcrystalline cellulose  conforming to these specifications.


Asahi Chemical Industry Co. (1966) Effect of ingestion of avicel-contained foods on living organisms. Unpublished report from Yoshitoshi Internal Seminar (Submitted to WHO by Asahi Chemical Industry Co., Ltd).

Baker, E.M. (1966) Microcrystalline cellulose: oral administration –

Rats. Unpublished report from Fitzsimmons General Hospital (Submitted

to WHO by FMC Corporation).

Baker, E.M. (1968) Microcrystalline cellulose: oral administration –

Humans. Unpublished report from Fitzsimmons General Hospital

(Submitted to WHO by FMC Corporation).

Batt, K.J. (1992) Avicel RCN-15 –   Salmonella/mammalian microsome

plate incorporation assay (Ames test). Unpublished report No. I91-1214

from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA

(Submitted to WHO by FMC Europe N.V.).

Behall, K.M., Lee, K.H., & Moser, P.B. (1984) Blood lipids and lipoproteins in adult men fed four refined fibers.  Am. J. Clin.Nutr., 39: 209-214.

Behall, K.M., Scholfield, D.J., Lee, K., Powell, A.S., & Moser, P.B. (1987) Mineral balance in adult men: effect of four refined fibers. Am. J. Clin. Nutr., 46: 307-314.

Bradlow, H.L., Michnovicz, J.J., Halper, M., Miller, D.G., Wong, G.Y.C., & Osborne, M.P. (1994) Long-term response of women to indole-3-carbinol or a high fiber diet.  Cancer Epidemiol. Biomarkers Prev, 3: 591-593.

CanTox Inc. (1993) Estimated consumption of microcrystalline cellulose and sodium carboxymethylcellulose from current and proposed food uses of Avicel cellulose gel.  Unpublished report dated December 1993, prepared by CanTox Inc. for FMC Corporation (Submitted to WHO by FMC Europe N.V.).

Carryer, P.W., Brown, M.L., Malagelada, J.-R., Carlson, G.L., & McCall, J.T. (1982) Quantification of the fate of dietary fiber in humans by a newly developed radiolabeled fiber marker. Gastroenterology, 82: 1389-1394.

Cifone, M.A. (1992) Mutagenicity test on Avicel RCN-15 in the L5178Y TK+/- mouse lymphoma forward mutation assay with an independent repeat. Unpublished report by Hazleton Washington Inc., Vienna, Virginia, USA (FMC Study No. 191-1230) (Submitted to WHO by FMC Europe N.V.

Cifone, M.A. (1994) Mutagenicity test on Avicel CL-611, E329N in theL5178Y TK+/- mouse lymphoma forward mutation assay with a confirmatory assay. Unpublished report by Hazleton Washington Inc., Vienna,  Virginia, USA (FMC Study No. 194-1834) (Submitted to WHO by FMC Europe N.V.)

Cohen, L.A., Zhao, Z., Zang, E., & Rivenson, A. (1996) Dose-response effects of dietary fiber on NMU-induced mammary tumorigenesis, estrogen levels and estrogen excretion in female rats. Carcinogenesis, 17: 45-52.

Egan, S.K. & Heimbach, J.T. (1994) Microcrystalline cellulose, MCC, E460(i). Part four: Exposure data – Estimated intake of MCC in the United Kingdom. Unpublished report dated April 11, 1994, prepared by TAS, Inc., Washington, DC, USA for FMC Corporation (Submitted to WHO by FMC Europe N.V.).

Eldridge, J.H., Gilley, R.M., Staas, J.K., Moldoveanu, Z., Meulbroek, J.A., & Tice, T.R. (1989) Biodegradable microspheres: vaccine delivery system for oral immunization.  Curr. Top. Microbiol. Imunol., 146: 59-66.

Eldridge, J.H., Hammond, C.J., Meulbroek, J.A., Staas, J.K., Gilley, R.M. & Tice, T.R. (1990) Controlled vaccine release in the gut-associated lymphoid tissues: I. Orally administered biodegradable microspheres target the Peyer’s patches.  J. Control. Release, 11: 205-214.

Ferch, H. (1973a) Innocuity of Elceme (R). Part I.  Pharm. Ind.,35(9): 578-583.

Ferch, H. (1973b) Innocuity of Elceme (R). Part II.  Pharm. Ind.,35(9): 658-661.

FMC Corporation N.V. (1996) Microcrystalline cellulose. MCC, Ins 460 (i). Technical and Scientific Dossier. Unpublished report from FMC Europe N.V., Brussels, Belgium, dated November 1996 (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1991a) Avicel RCN-15. Acute oral toxicity study in rats. Unpublished report No. I91-1217 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1991b) Avicel RCN-15. Acute dermal toxicity study in rats. Unpublished report No. I91-1219 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1991c) Avicel RCN-15. Primary eye irritation study in rabbits. Unpublished report No. I91-1218 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1991d) Avicel RCN-15. Primary skin irritation study in rabbits. Unpublished report No. I91-1220 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1991e) Avicel RCN-15. Skin sensitisation study in guinea pigs. Unpublished report No. I91-1216 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1992a) Avicel RCN-15. Ninety-day feeding study in rats. Unpublished report No. I91-1202 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1992b) Avicel RCN-15. Teratology study in rats (dietary). Unpublished report No. I91-1213 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1994a) Avicel CL-611. Ninety-day feeding study in rats. Unpublished report No. I92-1711 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1994b) Avicel CL-611. Teratology study in rats (dietary). Unpublished report No. I92-1712 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1996a) Avicel AC-815. Primary eye irritation study in rabbits. Unpublished report No. I95-2042 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1996b) Avicel AC-815. Primary skin irritation study in rabbits. Unpublished report No. I95-2043 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1996c) Avicel AC-815. Skin sensitization study in guinea pigs. Unpublished report No. I95-2044 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1996d) Avicel AC-815. Acute oral toxicity study in rats. Unpublished report No. I95-2040 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, C. (1996e) Avicel AC-815. Acute dermal toxicity study in rats. Unpublished report No. I95-2041 from FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Freeman, H.J., Spiller, G.A., & Kim, Y.S. (1978) A double-blind study on the effect of purified cellulose dietary fiber on 1,2- dimethylhydrazine-induced rat colonic neoplasia.  Cancer Res., 38: 2912-2917.

Freeman, H.J., Spiller, G.A., & Kim, Y.S. (1980) A double-blind study on the effects of differing purified cellulose and pectin fiber diets on 1,2-dimethylhydrazine-induced rat colonic neoplasia.  CancerRes., 40: 2661-2665.

Frey, J.W., Harding, E.R., & Helmbold, T.R. (1928) Dietetic investigations of edible pure cellulose.  Med. J. Rec., 127: 585-589.

Gillooly, M., Bothwell, T.H., Charlton, R.W., Torrance, J.D., Bezwoda, W.R., MacPhail, A.P., Derman, D.P., Novelli, L., Morrall, P., & Mayet, (1984) Factors affecting the absorption of iron from cereals. Br. J. Nutr., 51: 37-46.

Godara, R., Kaur, A.P., & Bhat, C.M. (1981) Effect of cellulose incorporation in a low fiber diet on fecal excretion and serum levels of calcium, phosphorus, and iron in adolescent girls.  Am. J. Clin.Nutr.,  34: 1083-1086.

Gordon, D.T., Besch-Williford, C., & Ellersieck, M.R. (1983) The action of cellulose on the intestinal mucosa and element absorption by the rat.  J. Nutr., 113: 2545-2556.

Hazleton Labs (1962) Microcrystalline cellulose; oral administration – Human. Unpublished report from Hazleton Labs, Inc. (Submitted to WHO by FMC Corporation).

Hazleton Labs (1963) Long-term nutritional balance study – Rats. Unpublished report from Hazleton Labs, Inc. (Submitted to WHO by FMC Corporation).

Hazleton Labs (1964) Microcrystalline cellulose: reproduction study – Rats. Unpublished report from Hazleton Labs, Inc. (Submitted to WHO by FMC Corporation).

Hillman, L.C., Peters, S.G., Fisher, C.A., & Pomare, E.W. (1985) The effects of the fiber components pectin, cellulose and lignin on serum cholesterol levels.  Am. J. Clin. Nutr., 42: 207-213.

Ismail-Beigi, F., Reinhold, J.G., Faraji, B., & Abadi, P. (1977) Effects of cellulose added to diets of low and high fiber content upon the metabolism of calcium, magnesium, zinc and phosphorus by man. Nutr., 107: 510-518.

Jani, P., Halbert, G.W., Langridge, J., & Florence, A.T. (1990) Nanoparticle uptake by the rat gastrointestinal mucosa: quantitation and particle size dependency.  J. Pharm. Pharmacol., 42: 821-826.

Jani, P.U., McCarthy, D.E., & Florence, A.T. (1994) Titanium dioxide rutile particle uptake from the rat GI tract and translocation to systemic organs after oral administration.  Int. J. Pharm., 105: 157-168.

Jenkins, P.G., Howard, K.A., Blackhall, N.W., Thomas, N.W., Davis, S.S., & O’Hagan, D.T. (1994) The quantitation of the absorption of microparticles into the intestinal lymph of Wistar rats.  Int. J.Pharm., 102: 261-266.

Kasper, H., Rabast, U., Fassl, H., & Fehle, F. (1979) The effect of dietary fiber on the postprandial serum vitamin A concentration in man.  Am. J. Clin. Nutr., 32: 1847-1849.

Kotkoskie, L.A., Butt, M.T., Selinger, E., Freeman, C., & Weiner, M.L. (1996). Qualitative investigation of uptake of fine particle size microcrystalline cellulose following oral administration in rats. Anat., 189: 531-535.

Kringsholm, B. & Christoffersen, P. (1987) The nature and the occurrence of birefringent material in different organs in fatal drug addiction.  Forensic Sci. Int., 34: 53-62.

Lawlor, T.E. (1996) Mutagenicity test with Avicel AC-815 in the Salmonella-Escherichia coli/mammalian microsome reverse mutation assay with a confirmatory assay. Unpublished report by Corning Hazleton Inc., Vienna, Virginia, USA (FMC Study No. I95-2047) (Submitted to WHO by FMC Europe N.V.).

LeFevre, M.E., Hancock, D.C., & Joel, D.D. (1980) Intestinal barrier to large particulates in mice.  J. Toxicol. Environ. Health, 6: 691.

Lewerenz, H.J., Bleyl, D.W.R., & Plass, R. (1981) Report on investigations in the second test year of continuous administration of microcrystalline cellulose into rats with their feed. Translation (and German original) of an unpublished report from the Academy of Sciences of the German Democratic Republic, Research Center for Molecular Biology and Medicine, Central Institute for Nutrition, Potsdam-Rehbrücke (Submitted to WHO by FMC Europe N.V.).

Linskens, H.F. & Jorde, W. (1974) Persorption of lycopodium spores and pollen grains,  Naturwissenschaften, 61: 275-276.

McKeon, M.E. (1992). Genotoxicity test on Avicel RCN-15 in the assay for unscheduled DNA synthesis in rat liver primary cell cultures with a confirmatory assay. Unpublished report by Hazleton Washington Inc., Kensington, Maryland, USA (FMC Study No. I91-1229) (Submitted to WHO by FMC Europe N.V.).

Murli, H. (1992) Mutagenicity test on Avicel RCN-15  in vivo    mammalian micronucleus assay. Unpublished report by Hazleton     Washington Inc., Kensington, Maryland, USA  FMC Study No. I91-1228)    (Submitted to WHO by FMC Europe N.V.).

Murli, H. (1994a) Mutagenicity test on Avicel pH101 Pharmaceutical in     an  in vivo mouse micronucleus assay. Unpublished report by Hazleton     Washington, Inc., Vienna, Virginia, USA (FMC Study No. I94-1837)     (Submitted to WHO by FMC Europe N.V.).

Murli, H. (1994b) Mutagenicity test on Avicel CL-611 in an  in vivo    mouse micronucleus assay. Unpublished report by Hazleton Washington,     Inc., Vienna, Virginia, USA (FMC Study No. I94-1835) (Submitted to WHO     by FMC Europe N.V.).

Niemi, M.K., Keinänen-Kiukaanniemi, S.M., & Salmela, P.I. (1988)     Long-term effects of guar gum and microcrystalline cellulose on     glycaemic control and serum lipids in Type 2 diabetes.  Eur. J.     Clin. Pharmacol., 34: 427-429.

Pahlke, G. & Friedrich, R. (1974) Persorption of microcrystalline     cellulose,  Naturwissenschaften, 61: 35.

Pallotta, A.J. (1959) Acute oral administration – Rats; and acute     intraperitoneal administration – Rats, of microcrystalline cellulose. Unpublished report from Hazleton Labs, Inc. (Submitted to WHO by FMC Corporation).

Schmitt, D.F., Frankos, V.H., Westland, J., & Zoetis, T. (1991) Toxicologic evaluation of Cellulon fiber; genotoxicity, pyrogenicity, acute and subchronic toxicity.  J. Am. Coll. Toxicol., 10: 541-554.

Schreiber, G. (1974) Ingested dyed cellulose in the blood and urine of man.  Arch. Environ. Health, 29: 39.

Signorin, J. (1996) Avicel AC-815. Acute inhalation study in rats. Unpublished report No. I95-2045 by FMC Corporation Toxicology Laboratory, Princeton, New Jersey, USA (Submitted to WHO by FMC Europe N.V.).

Simon, L., Shine, G., & Dayan, A.D. (1994) Effect of animal age on the uptake of large particulates across the epithelium of the rat small intestine.  Int. J. Exp. Pathol., 75: 369-373.

Steege, H., Lewerenz, H.J., Philipp, B., & George, J. (1980) Characterization of cellulose powders with special attention to the physiological aspects. International Dissolving Pulp Conference, German Democratic Republic, 5, 169-183.

Tomashefski, J.F., Hirsch, C.S., & Jolly, P.N. (1981) Microcrystalline cellulose pulmonary embolism and granulomatosis. A complication of illicit intravenous injections of pentazocine tablets.  Arch.Pathol. Lab. Med., 105: 89-93.

Tusing, T.W., Paynter, O.E., & Battista, O.A. (1964) Birefringence of plant fibrous cellulose and microcrystalline cellulose in human stools freezer-stored immediately after evacuation.  Agric. Food Chem., 12(3): 284-287.

Volkheimer, G., Schultz, F.H., Lehmann, H., Aurich, I., Hubner, R., Hubner, M., Hallmayer, A., Munch, H., Opperman, H., & Strauch, S.(1968) Primary portal transport of persorbed starch granules from the intestinal wall.  Med. Exp., 18: 103-108

Walters, M.P., Kelleher, J., Findlay, J.M., & Srinivasan, S.T. (1989) Preparation and characterisation of a [14C]cellulose suitable for human metabolic studies.  Br. J. Nutr., 62: 121-129.

Yartsev, N.M., Ivanova, V.S., Altymyshev, A.A., Sarybayeva, R.I., & Vasil’kova, T.V. (1989) Anatomical and histological state of rats given microcrystalline cellulose in long-term experiments. Izvestiya AN Kirgizskoi SSR, 3: 63-65.

Zeltner, T.B., Nussbaumer, U., Rudin, O., & Zimmermann, A. (1982) Unusual pulmonary vascular lesions after intravenous injections of microcrystalline cellulose. A complication of pentazocine tablet abuse.  Virchows Arch. [Pathol. Anat.], 395: 207-216.


Learn The Phenomenon Of Similimum In Terms Of ‘Functional Groups’ Of Constituent Drug Molecules

Diseases, other than those originating from genuine nutritional deficiencies and genetic abnormalities, are caused by diverse types of exogenous or endogenous pathological molecules, which inhibit the normal actions of essential biological molecules by binding to them. Exactly, it is the ‘functional groups’ of pathological molecules that bind to biological molecules and produce pathological inhibitions, which are expressed through subjective and objective symptoms we call as ‘diseases’.

Constituent chemical molecules of a drug substance interact with our body by binding their diverse types of ‘functional groups’ or ‘moieties’ with specific biological target molecules in our organism and modifying their actions. This interaction is determined by configurational as well as charge affinities between those functional groups and biological target molecules. It is the number of types of biologically active ‘functional groups’ or ‘moieties’ available in a drug substance that decides whether it is a ‘single’ drug or ‘multiple’ drug.

Different types of ‘functional groups’ of individual molecules contained in a drug substance bind to different biological target molecules, and produce different types of modifications. It is this ‘modifying’ or ‘inhibitory’ actions that produce molecular states of pathologies during drug proving, which are expressed through diverse types of subjective and objective symptoms.

Similar functional groups being part of different drug molecules of even different drug substances can bind to same target molecules and produce similar bio-molecular modifications and similar symptoms.

When a drug molecule has functional groups or moieties similar to those of a pathological molecule, they can attack same biological targets, and symptoms they produce would be similar. In such a situation, the drug molecule is said to be ‘similimum’ to that pathological molecule. Obviously, according to scientific perspective, we should understand the concept of ‘similimum’ in terms of similarity of ‘functional groups’ or ‘moieties’ of pathological molecules and drug molecules.

Potentization is exactly a process of controlled ‘host-guest’ interactions, by which the three-dimensional configuration of ‘functional groups’ of individual constituent molecules of drug substances (host) are imprinted into a hydrogen-bonded supra-molecular matrix of water-ethyl alcohol molecules (guest) as ‘nanocavities’.

These nanocavities or ‘molecular imprints’ can bind to and deactivate any functional group having configuration similar to that of original ‘host’ molecule imprinted into it. As such, a potentized drug can act as biological antidote towards any pathological molecule, if the drug and disease were capable of producing ‘similar’ symptoms, which actually mean, they contain similar ‘functional groups’.

I hope, scientific meaning of ‘similia similibus curentur’ is well explained here, and scientifically viable answers provided for the THREE fundamental questions of homeopathy- what happens during potentization, what are the active principles of potentized drugs, and what is the exact molecular mechanism by which potentized drugs produce a therapeutic effect. Answers to all other secondary questions could be easily evolved once you comprehend these fundamental answers.