Above all, Aloe vera acts upon cells within the body, usually by stimulating them into extra activity, such as growth, replication, and secretion. In the case of immune cells it stimulates theengulfing of foreign impurities and the release of special chemical messengers. In a few situationsAloe’s action is to discourage the release of unwanted chemical messengers. The main point here is that Aloeconveys subtle information and encoded instructions for cellular activities of many kinds. It does not heal through Nutrition, although many companies which sell it claim that it does. Therefore, to get the full benefits of Aloe it should be used in conjunction with nutritional supplementation.

1. What Aloe is not – It is not a Nutritional Supplement

Promoters of Aloe products often promote them on the grounds that they are capable of contributing substantially to a person’s nutritional status. This is not true. Typically, Aloe is said to contribute valuable minerals, vitamins and amino acids. Sometimes the essential fatty acids are also mentioned. To begin to understand why this is not valid, it helps to consider the concentration of solids in Aloe vera juices. Aloe vera Gel, compared with most plant juices and extracts, is a very thin fluid containing only a very low concentration of soluble solids. Plant juices and extracts made from forage crops, such as grass or lucerne, normally have a much higher concentration of soluble solids, perhaps in the region of 7 to 10% by weight, compared to the concentration in Aloe vera Gel of only 0.46 to 0.6%. This may be fairly ascribed to the fact that the Aloe vera Gel is a water-storage part of the plant Even Aloe Whole Leaf Extract averaging 1.25% solids, is quite weak in terms of solids, even though it has powerful biomedical properties. If you consume 10ml per day of Aloe Gel at average strength, then you are taking about 0.055g (55mg) Of solids. 50ml (a substantial dose) will give you 0.275g (275mg). With the Aloe Whole Leaf Extract 10ml will give you about 0.125g (125mg) and 50ml will give 0.625g or 625mg. For nutrition to be significant at all in these tiny quantities. the Aloe would have to be very concentrated in respect of some important nutrient or nutrients with very low daily requirement. Therefore, we look briefly below at the principle nutrients that are present in these small amounts of Aloe solids.

Total solids and free sugars

According to researchers Pelley and Wang at the University of Texas Medical Branch, simple sugars are a fairly high proportion among the total solids in the Aloe Gel fluid, i.e. 0.28% by weight, or about half of the total dissolved substances of the fluid. These simple sugars have been analysed as predominately glucose (about 95% of them), with 5% of fructose, which is fruit sugar. Having accounted for 100% of the simple free sugars in this way, there would appear to be little scope for finding any other simple sugars such as mannose, xylose, arabinose, rhamnose or di- or trisaccharides. It is clear that any of these that are present in the free state must be there in only trace concentrations. So far as glucose and fructose are concerned, it would seem that one can virtually forget them as significant contributors to Aloe’s unique bio-medical actions. Glucose is such a common sugar and its properties are so well-known that it is not credible that a 0.28% solution of glucose could have significant effects. For example, an individual consuming 50ml of Gel fluid per day will be consuming only 133mg of glucose and 7mg of fructose from the Aloe source. Compared with, say, the 50g of glucose that is taken for the glucose tolerance test, the amount is clearly quite negligible.

Free form amino acids

Dismissing free sugars as a significant factor, the Gel fluid contains amino acids. Different authors have reported finding them, from 17 to 20 in number, but then plant biochemists would expect almost any plant juice to contain them, for they are, of course, the precursors of plant proteins. One author reports that arginine was the most abundant of them while another that aspartic acid, glutamic acid, serine and histidine were the most abundant. The literature shows up some uncertainty among researchers as to whether any of these amino acids can have specific bio-medical activities ascribed to them. One author considers that they contribute to the wound-healing property of Aloes and another that they contribute to the stimulation of phagocytosis which Aloe produces. The latter property was being ascribed to the two individual amino acids cysteine and proline. The difficulty with these ideas as an approach to explaining the actions of Aloe is that any effect of the amino acids would have to be rather non-specific, and, since virtually all plant extracts contain free amino acids, it is hard to see just how this sort of theory would even begin to explain the individuality of Aloe, and its near-uniqueness of action. Moreover, a great many of our foods contain some free amino acids, and, whether our digestive system is working well or not, some considerable quantities of free amino acids are always being generated in our intestines. True, one cannot reject the amino acid theory out of hand, because there is no doubt that individual free amino acids can have therapeutic effects when given in quantities ranging from 1 g to 6g per day. A daily dietary protein intake, even if it is only 60g per day, quite a low figure, will deliver an average of 3g of each of the 20 principal amino acids that make up proteins. Once again, given that the total solids in a 50ml dose of Aloe vera Gel fluid at a 0.6% concentration would be only 300mg and that any individual free amino acid cannot possibly represent more than a trace percentage of those solids, the amino acid theory comes to look very tenuous, indeed.

Organic acids

The next group of substances we may consider is the organic acids, i.e., acids like lactic, citric, isocitric, malic, succinic etc. According to researchers Pelley and Wang these amount to 0.143% of the Gel fluid, considerably higher than any possible concentration of free amino acids. Nonetheless a 50ml dose of Aloe Gel fluid would only yield just over 70rng of this whole fraction, whic is the sum total of all the organic acids present. Certainly, they are substances not noted for having any very marked physiological effects when taked by mouth.Nutricionists very frequently use mineral citrates as nutricional supplements. In this context some 3000 mg/day of citrate may be given just as a carrier for the mineral being supplemented and the intake of citrate can rise in some instances to 6000mg/day. These levels of intake do not produce any known physiological effects, and, indeed, none would be expected, since the human adult produces and destroys a very large amount of citric acid each day, possibly as much as 1000g per day, a quantity which makes the above administered doses negligible. In this context, any contribution of citric acid to the body via Aloe Gel fluid appears completely negligible. The same is true of the other organic acids named above, because they are all interconverted in sequence.

Minerals in Aloe Gel and Whole Leaf Extracts

Aside from the specific references given above to the salts of calcium and magnesium, the question arises as to whether it is possible that the mineral constituents of Aloe make any significant contribution to Aloe’s bio-medical effects. Again, the concentrations are very low and minerals are so readily available from other sources, especially vegetables, of which one is likely to consume so much more than of any Aloe preparation. The concentration of metal cations (positive ions) in Aloe Gel fluid is given by Pelley and Wang as 0.103%, or just over 50mg in a 50ml dose of Aloe Gel fluid. Bouchey and Gjerstad, in a paper entitled “Chemical Studies of Aloe vera Juice” reported upon the relative levels of the major minerals in the juice.

Using their figures, one can derive the proportions of the 50mg mineral contribution given above. These would be potassium 13.2mg, calcium 9.4mg, and sodium 3mg. These figures compare with likely dietary figures from a good wholefood diet of 6000mg for potassium, 1000mgfor calcium and 500- 1000mg for sodium. Magnesium is only likely to be delivered at about 2 to 4mg per day compared to the intake from a wholefood diet of about 400mg. Even if a concentrated form of Aloe Gel fluid were used, the mineral contributions would remain absolutely minimal, with far cheaper items, like rhubarb and lettuce being far more efficient at supplying them. The mineral contribution from Aloe can safely be disregarded as having any possible bearing at all upon the sources of Aloe´s magic.

Special mineral salts of organic acids

Some of the substances in Aloe claimed by researchers to have physiological actions are mineral salts of organic acids. Some japanese researchers led by Nishioka found stimulant effects from A. vera extracts on the excised heart muscle of laboratory animals and identified the active principle as calcium isocitrate. Also, several Japanese workers have identified magnesium lactate as being one of the substances in Aloe which inhibits gastric secretion, called aloe-ulcin. These results, like some of the others that have been cited above, are really unexpected and need further explanation because of the very low concentrations of these organic salts that could be present in an Aloe Gel fluid and because the compounds mentioned are by no means peculiar to the Aloe plant, being common metabolites throughout the animal and plant worlds. Because of these considerations, it seems really unlikely that either calcium isocitrate or magnesium lactate have any key or central role in creating the special pattern of physiological properties which characteristically belong to the Aloe plant.

Vitamins

In common with all plant juices Aloe vera extracts contain just trace levels of various vitamins. Given the extremely low concentrations and the rather small doses of Aloe vera normally taken, they are most unlikely to make any significant contribution towards human vitamin requirements.

2)So How Exactly does Aloe Act upon Cells?

2a) The Immuno-Stimulant Effects

Issue No 1 gave a clear statement about the effect of Aloe in stimulating the engulfing of foreign impurities by macrophages, the process known as phagocytosis. Issue No 12 explained the actions of the polysaccharide fraction of Aloe and its role in bringing about the immune response. This polysaccharide fraction, which does not often represent much more than 10% of the total solids of Aloe extracts, seems clearly to exert its prime immunostimulant effect at the level of the macrophage. It is almost certain that there are other immuno-stimulatory substances in Aloe in addition to the high molecular weight polysaccharides. One can deduce this from the fact that even Whole Leaf Extracts and Concentrates which have been heavily treated with ceilulase enzyme, in which the high molecular weight polysaccharides have been broken down, possess remarkable immuno-stimulant activity. There are also reports that some anthraquinones (which are concentrated in the Exudate Fraction of Aloe, but which usually survive at very low concentrations in the Gel or the Whole Leaf Extract) possess immunostimulant activity. There is also interesting speculation that the proteoglycan (or glycoprotein) fraction of Aloe vera of molecular weight 10,000 to 50,000 may possess immuno-stimulant activity in the same way as has been clearly demonstrated in the case of Aloe arborescens (“Aloctin A, an Active Substance of Aloe arborescens Miller, as Immunomodulator”, imanishi, K. 1993). Nevertheless, various workers have now demonstrated an effect which can easily be produced with high molecular weight glucomannan from Aloe, which is exerted upon the macrophages. In addition to increasing macrophage activity directly, the macrophages are caused to secrete messenger substances capable of diffusing through tissues to stimulate different activities on the part of other cell types within the immune system.

The three special chemical messengers produced by macrophages when they have been stimulated by glucomannan from Aloe are called “kinins” or “cytokines”, words that signify that their effects have much to do with movement or action. The scientific names of these substances might be off-putting to some, of course. Bear in mind though, that as a user of Aioe one has absolutely no need to memorize any of these details, which are provided here only for reference, and for completeness and accuracy. The same information could be given about them referring to them just as 1,2,3, etc.

Tumour Necrosis Factor α

Has the effect of inducing tumour regression, i.e., making the tumour shrink and also bringing about inflammation. Its role is presumably of great importance in activating immune cells to attack and destroy tumours.

Interleukin 1 β
Activates T Lymphocytes (another important cell type within the immune system). Production of fever and inflammation.

Interleukin 6

Promotes inflammation and activates B Lymphocytes.
The macrophages can also directly stimulate the T lymphocytes to produce two further substances: These are;

Interleukin 2

This stimulates the differentiation ofT and B lymphocytes (i.e. their development from earlier stages in their growth) and also induces ceiï multiplication among the lymphocytes.

Interferon γ

Interferon was much publicised a few years ago as a potential anti-cancer agent, but it never quite fulfilled its early promise in that role, its importance is recognised, however, in the anti-viral applications of Aloe products.

View these cytokines just as a variety of small sized molecules which carry messages. They can be described as “soluble proteins or glycoproteins produced by leucocytes (white cells), and in many cases other cell types, which act as chemical communicators between cells, but not as effector molecules in their own right”. The fact which is of interest here is simply that the activation of different processes and different cell types within the immune system starts with the stimulation of the macrophages. These respond by secreting the three special cytokines listed above. These seem to start a cascade of events whereby additional cell types within the immune system are brought into the fray each to perform their own characteristic functions. Each contributes to the sum total of the immune system’s actions.

Any reader wishing to find out more detail about these important cytokines that are produced in response to Aloe can consult ‘The Cytokine Factsbook” by R. Callard and A. Gearing (1994), published by Academic Press.

2b) The Anti-Inflammatory Effects

These have been discussed, of course, in Issue 2, and the low molecular weight active principles were identified as being (1) sterols (2) anti-histamine (3) salicylates. The enzyme protein bradykininase was also related to inflammation reduction. It is now clear that the glucomannan of Aloe, which is its best identified and best researched active principle, also plays a role in the anti-inflammatory effect. The precise fraction or fractions of the glucomannan which exert this effect have yet to be clearly identified, but it seems clear that some of them at least are present in the middle fraction of molecular size and weight. These fall in between the smaller molecules which have anti-diabetic action and the largest molecules which embody the prime immunostimulant activity. Hence, the anti-inflammatory activity must be ascribed to a whole complex of bio-active molecules. This is very much in accord with Professor Robert Davis’s “Conductor and Orchestra” theory of Aloe’s actions, in which the whole plant or its juice is seen to be substantially greater than just the sum of its parts. (Described in a pamphlet ‘The Conductor – Orchestra Concept of Aloe vera”, published from the Pennsylvania College of Podiatric Medicine).

As we have already considered the nature of anti-inflammatory active principles in Aloe, we may briefly consider here their mode of action at cellular and metabolic level.

The occurrence of inflammation in the first place may be a response to physical injury of tissue, chemical toxic damage to tissue, or cellular damage arising from bacterial toxins. However, the effects of these sources of damage are mediated through quite a number of different chemical messengers. These include;

Prostaglandins of the Series 2 (hormones)
Leukotrienes (cytokine)
Interleukins (cytokine)
Tumour Necrosis Factor (cytokine)
Bradykinin (cytokine)
Histamine (active amine)
“Complement”
Factors
“Permeability” Factors

Once again, there is absolutely no need for the user of Aloe to familiarize him or herself with these names. They are just presented to show the numerous factors involved in the process. In addition to these chemical messengers which tend to induce inflammation, further inflammatory effects are caused by the breakdown products from damaged and dead cells. These includes enzymes released from “lysozomes”, (which are small intracellular bodies) and breakdown products from the nucleic acids of the cell nuclei.

Of the vast number of know anti-inflamatory drugs,most, including aspirin, appear to act by inhibiting the production of the hormones called prostaglandins. They usually seem to inhibit prostaglandin synthesis “across the board”, so that whole group of these hormones is inhibited, not just the inflamatory ones. This is obviously undesirable. Some natural therapeutic agents (such as the pineapple enzyme, bromelain, which is strongly anti-inflamatory) inhibit much more specifically those prostaglandins which are clearly inflammatory. That is a real advantage. This situation does not yet appear to have been worked out for Aloe. We do know, however, that Aloe inhibits pprostaglandin synthesis, as reported by Raine, T., London, M., Goluch, K., Heggers, J., & Robson, M. (1980) , Heggers, J., & Robson, M. 1983 and by Grindlay D and Reynolds, T (1986). One may speculate that the salicylates in Aloe are responsible for this, because this would accord with their close relationship to aspirin.

The presence of bradykininase in Aloe clearly implies that the pro-inflammatory cytokine called bradykinin is reduced by Aloe in this way (Fujita, K., Teradaira, R., & Nagatsu, T. 1976, Yagi, A., Harada, N., Iwadare, S., & Nishioka, 1.1982, and Yagi, A., Harada, N., Shimomura, K., & Nishioka, I., 1986).

Sterols reduce inflammation by reducing the vascular swelling and increased vascular permeability associated with inflammation, and hence they reduce the oedema and swelling of tissues during inflammation. This in turn reduces redness and pain. Furthermore, they inhibit the migration of white blood cells to the site of injury, reduce phagocytosis and the proliferation of blood vessels and of fibroblast cells.Aloe contains the three potent plant sterols,, Lupeol β -Sitoserol and Campesterol, which appear to act in reducing inflammation in a way realy quite similar to the steroid drugs as show in “ Aloe Vera, Hydrocortisone and Sterol influence on Wound Tensile Strenght and Anti-inflammation. Davis R.H. Didonato, J.J. Johnson, & W.S., Steawart, C.B. (1994)

The fourth major way in aloe appears to reduce inflammation is by an anti-histamine effect. This is likely to be archieved by either inhibiting the production of histamine or by activating its removal. Magnesium (even though a dose of Aloe delivers so little of it) has been proposesd as an inhibitor of hisidine decarboxylase, the enzyme which forms histamine from the amino acid histamine. It has also been sugested that magnesium and salicylate might be synergistic (Le that they may produce a larger effect together than the sum otal of their individuals effects). This is as much as we know at present about Aloe´s anti-histamine action.

Also there is no clear published evidence about the mechanism by which either anthraquinones or glucomannan reduce inflammation. Nonetheless, it appears that Aloe may well be so special in its antiinflammatory role simply because of the number and range of the different anti-inflammatory factors which it contains. The different anti-inflammatory factors clearly (from the above) do not work by the same mechanism or upon the same parts of the cell. Rather, many of them work by different cellular mechanisms, or by a different range of mechanisms. This means, that with Aloe, several different parts of the inflammatory mechanisms of the tissues are “calmed down”, each of them by a different component of Aloe’ armoury of at least six anti-inflammatory active principles. Obviously, the resulting antiinflammatory effects often can be greater and more impressive than the results from any single prescription drug which is acting only on one aspect of the inflammatory process.

The effects of Aloe on the actual processes of tissue inflammation may or may not be equal or superior to the effects of steroid drugs. However, in this context the negative effects and side-effects of steroid drugs have to be borne in mind. These drugs not only suppress inflammation but also suppress the healing of wounds and are strongly immuno-suppressive. These are most undesirable effects and represent a very high price to be paid for the reduction in inflammation which is achieved. Professor Davis and his colleagues have shown that, whilst hydrocortisone suppresses inflammation and also suppresses healing, Aloe vera reduced inflammation and at the same time stimulated the healing of wounds | very strongly. This is possible because, whilst the steroids in Aloe vera work quite like hydrocortisone, Aloe
vera also contains strong healing and cell-proliferative effects which more than outweigh the suppressive effects of the Aloe phytosterols. Moreover, the Aloe, as we have seen, also contains very powerful immuno-stimulant substances which do much more than compensate for any from Aloe’s phytosterols, leading to a strongly immuno-stimulant effect overall. Once again, the ways in which these various actions work together seems to confirm strongly the viewpoint that the various active principles of this plant work in a synchronous and co-operative way, hence re-inforcing Professor Davis’s “Conductor – Orchestra” concept. There is absolutely no drug that can do that. With Aloe, indeed, “The Whole” apparently, is worth more than the sum of its parts. This is now more than just a saying – it can be seen
from the scientific and medical evidence.

2c The Healing Effects of Aloe

This special action of Aloe was discussed in detail in Issue 4, which explained the effects upon the cells called fibroblasts, which are involved in forming the new tissues required for the healing of wounds. The beneficial effects were traced once again to the glucomannan, but also to the plant hormones auxin and gibberellin. Obviously, these are the components which have the ability to overcome and to reverse the suppressive effects exerted upon healing by Aloe’s phytosterols. That explanation in Issue 4 contained much of what is known about these particular actions at cellular level.

Most authorities agree that the mechanism of increased wound healing really is still obscure and that what we have is just a set of reasonable theories about it. Whatever the mechanism, it is clear that glucomannan plays an important part and that the effects include wound margin shrinkage and a growth of new tissue called “granulation tissue”. This is accompanied by the spread of new blood vessels through the wound area and there is an increase in synthesis of collagen, the fibrous protein which connective tissues need to give them strength.

It is not entirely clear what molecular size fraction of Aloe polysaccharide is responsible for the healing action. Having identified physiological roles for the smallest and largest sizes, one might well expect to find this activity in the region 50,000 up to one million molecular weight. However, Tizard, I., Busbee, D., Maxwell, B. & Kemp, M.C. “Effects of Acemannan, a Complex Carbohydrate, on Wound Heaiing in Young and Aged Rats” (in “Wounds” Vol 6, No. 6 Nov. – Dec 1994) reported healing activity specifically in the commercial product Acemannan, which contains high molecular weight material. He ascribes this action of an Aloe component to its ability to stimulate macrophages to produce cytokines, in just the same way as the immuno-stimulant action. The cytokines that are relevant to wound healing include some of those listed above under the heading of immuno-stimulation, such as Tumour Necrosis Factor a, Interleukin 1(3, and Interleukin 6. It appears that some of these messengers may be chemical attractants for macrophages and hence may be effective at bringing more macrophages to the site of injury. They also have been found to stimulate fibroblast multiplication. Hence, we have two alternative theories about the multiplication of the all-important fibroblast cells within the injury, one based upon glucomannan stimulating the fibroblasts indirectly via macrophage action (Tizard) and the other (Davis) involving direct stimulation of fibroblast by glucomannan. Since macrophages do produce a specific fibroblast growth factor (FGF), it is inherently likely that macrophages do have some role in the fibroblast response.

Still other factors produced from macrophages induce angiogenesis (the growth of new small blood vessels to supply the wound area). These include Interleukin 8 and another factor with the abbreviated name PDGF (Platelet Derived Growth Factor), which also has the ability to stimulate the growth and division of connective tissue cells.

It therefore seems at this stage of knowledge that there are multiple mechanisms involved in the wound healing response of Aloe.

2d The Digestive Effects of Aloe

The digestive effects of Aloe are among the most important actions of the plant and yet we really have no physiological studies to indicate how these are mediated. It is inherently probable that the gastrointestinal system benefits from both the immuno-stimulant and anti-inflammatory actions. The gut contains an amazing array of immune “lymphoid” tissue. There are major concentrations of this tissue in a few places, such as the so-called “Peyers patches” of the small intestine and the appendix. The latter is illustrated in Figure 2. However, no part of the alimentary system is left unprotected by the immune system and the intestines in particular have small dense areas of lymphoid cells spread through their tissues in an irregular fashion. This is evidence of the intestines being such an important area of direct
contact between the body and its environment that the immune defences have to be well marshalled there. It is inherently likely that the performance and integrity of the gut depend to great degree upon the strength and activity level of these immune defences. This may well be one way in which Aloe aids gastro-intestinal health. The antiinflammatory effect will also be marshalled whenever the early adverse and pathological changes begin in the gut, and Aloe may well enable such adverse changes to be extinguished before they give rise to troubles. However, the work of Dr Bland, mentioned in Issue 3 of these Newsletters, suggests strongly that there may well be another, more direct action of Aloe upon the digestive organs, whereby their vitality is toned up and their secretory functions are normalized. We have no hint as yet of just how these benefits are produced through actions at cellular level.

3) Aloe’s Effects upon Drug Action

A further action of Aloe, though one likely to be of no more than passing interest to Practitioners of Alternative Medicine, is that of potentiating the effects of orthodox drug medicines. This was first demonstrated by Davis RH, Parker WL, Sampson RT & Murdoch DP (1991) in “Aloe Vera as a Biologically Active Vehicle for Hydrocortisone Acetate “ J Am podiatr Med Assoc 81 (1)Since then it has become clear that Aloe can aid in the penetration and delivery of other orthodox drugs and can potentiate them in ways that result in the desired response being obtained with a lower drug dose than would be required ordinarily. Practitioners who do not use drugs will not be impressed af all. However, there may be cases where drug use is inevitable and where it is better to be able to employ the drug at a reduced dose.

4) The Overall Picture of Aloe’s Actions

Diagrammatic Pilot of the Pattern of Aloe´s Actions

We now look at the different actions of Aloe in the form of a diagram which helps to understand the relationships between them. This diagram in Figure 3 summarizes the sequences of events which lead to the three prime actions of Aloe. The hypoglycaemic (antidiabetic effect) is also included within this diagram. The reader is asked to please trace the pathways involved in generating these actions as follows. Much of what has already been discussed is summarized in these paragraphs.

1) Bradykininase, steroids and antiprostaglandin substances in Aloe lead to the overall antiinflammatory effect. As an anti-histamine action by components of Aloe has also been mooted in some literature, that too has been included.

2) The main polysaccharide rich fraction of Aloe, which is a mixture of glucomannans and glycoproteins, stimulates cell activity by interacting with cell-surface receptors as has been explained earlier. This effect influences the cells of the immune system, but specifically, lymphocytes, neutrophils and macrophages. This result, combined with the effects of increased cell numbers, which result from Aloe’s mitogenic (or cell-multiplying) effect, give us the totality of the overall immune response to Aloe. This sequence is followed through in the central horizontal path on the diagram.

3) At the same tin e plant growth factors, named gibbereilins and auxins, together with the mannoserich mannans and glycoproteins stimulate a variety of cell types to divide. It is clear that a number of immune cell types are included within that effect and also the fibroblasts, which give rise to the healing response within damaged tissues. The result of this cell division, of course, is increased cell numbers, within the immune system and also among the fibroblasts. The increased numbers of immune cells make their contribution to the overall immune response ehilst the increases in the numbers of fibroblasts bring about the healing response in damaged tissues. This sequence is followed through in one of the lower
horizontal paths on the diagram.

4) As has been recounted already, the macrophages, upon being stimulated in their activities bymannans and glycoproteins, release two chemical messengers called interleukin-1 and tumour necrosisfactor, and thereby further increasing the division and activity of other cells, including the fibroblasts whichare responsible for healing. This is believed to have the end-result of enhancing the healing effect. This sub-pathway is traceable through the backward-directed arrows in the lower central part of the diagram.

5) As an additional effect, the hypoglycaemic effect has also been included, although its mechanism is less certain. It is worth noting, however, that increasing cell division calls for increasing synthesis of cell constituents to form these new cells. It therefore implies that metabolism is being strongly directed, under the influence of Aloe, to synthetic activity rather than breakdown activity. The synthesis of cell constituents, leading to their accumulation, is known as “anabolism” or an “anabolic effect”. The opposite effect, that of encouraging breakdown of cellular constituents, would be called “catabolic”. It would seem, therefore, that the general tendency of cells acting under the influence of Aloe is towards anabolism. Not only does cell division absolutely require this, but it is also a known metabolic influence of gibberellins to encourage protein synthesis, and hence, encourage the build-up of cellular material. Moreover, the receptor on the fibroblasts which unites with mannan, is one which also accepts the “insulin-like growth factor”. Insulin in an abundantly anabolic hormone, which again, accentuates Aloe’s connection with anabolic, rather than catabolic effects. The inference which may be drawn from this, at least tentatively, is that the general nature of Aloe’s effects are anabolic. This general tendency could well be at the route of the inhibition of gluconeogenesis by Aloe, which has been reported as being the way in which Aloe lowers the blood sugar of hyperglycaemic individuals. This probable mechanism is represented in the bottom right hand part of the diagram.

After these steps have occurred, the prime actions of Aloe represented in the diagram can start to influence medical conditions such as those listed out against the headings of ‘Inflammation’’, “immunostimulant” and “healing action” at the start of this Chapter. Influencing the health status of the patients in these conditions and reducing their symptoms therefore comes at the end of the cascade of events being described.

The Wholistic and Vitalistic Implications of Aloe’s Actions

immunological and pathological terms, in other words, according to the thinking and language of the Medical Sciences. However, Aloe’s virtues appeal to a great many people who do not necessarily subscribe to all the precepts of orthodox medicine. These people are likely to say that they use Aloe “for its cleansing action”, or for its “revitalizing effects”.How is it possible that Aloe, as well as doing all that has been described in therms of medical and cellular effects that have been observed and studied by medical scientist , can also accomplish these less well defined functions that carry weight within Alternative and Complementary Medicine. This author does consider that these things are mutually compatible.

So far as “cleansing” is conserned, this is generally understood to be the process of clearing out both metabolic waste products and enviromental toxins that have entered the body and be taken up by its cells. Toxins produced by intestinal bacteria and then absorbed, also have a part to play. The hypothesis that lies behind the concept of cleansing is, briefly, as follows. Innaturopathicterms, the factor which mos compromisesbodily health is the accumulation of toxic waste and poisons in the living cell. The mechanism by which these substances produced effects could never be specified by the early naturopaths. It is now clear, however, that what lay at the foundation of their mental concepts about this was the inhibition of cell enzymes, especially those which break down foods to yield energy, those which synthesise proteins, including the enzymes themselves, those concerned in the synthesis and maintenance of the nucleic acids, and those concerned with the formation and maintenance of the external and internal cellular membranes. These are the parts of the living processes of the cell which are the most vulnerable to damage by toxins. All such damage contributes to making the cell inefficient and ineffective where the cell was vital and active before. Cells become moribund and die under the influence of toxins. The event of cel! death is preceded by a time when the cell is hypoactive (i.e. underactive) on account of its load of toxins. Most particularly the energy-generating mechanisms of the cell are damaged or hindered. The cell has less energy to work with. Its processes are slowed, its respiration, its synthesis of proteins, its ability to repair itself and replace its parts, and, most important, its ability to maintain its own internal environment, with the correct concentrations of sodium and potassium, calcium and magnesium.These are the processes of chronicity. It is a process which leads the body towards lowered vitality and activity.

In the naturopathic philosophy, onward progression of toxicity and of the chronic condition is a general disease-encouraging process. Some types of toxin affect one or more tissues or organs preferentially. In other cases the toxic effect is non-especific as to tissue type. The body organ or system fails and hence what disease develops then depends upon constitutional and inherited factors that are peculiar to each individual. It does mean, however, that it is generally true that the chronic diseases can be avoided by avoiding getting into toxic and chronic conditions.

Aloe vera, as we have seen, activates the immune cells, and in particular, it activats the scavening macrophages and neutrophils which carry out clean-up operations. This role the immune system makes it a great detoxifier. Those of them which operate within the confines of the lymphatic system, in the lymph glands, actually engage’ in cleaning up the lymph as it flows from the tissue drainage areas towards reentry into the blood-stream.

Aloe, as we have seen, also activates cells into a growth and replication phase, accompanied by much protein synthesis and the general build-up of tissue constituents. This is what has been termed “anabolism”. Cells in this positively activated, constructive and reproductive phase have increased activity and this is emphasised by their increased oxygen consumption. Such activated cells have heightened metabolism and have moved far from the chronic state. It is therefore a fair interpretation of the actions of Aloe that it moves cells away from hypo-active and therefore chronic conditions towards the highly active states in which detoxification occurs readily due to the cell’s favourable energy supply. Returning again for a moment to the condition of the immune system, it is a matter of clinical observation that patients with good and active immune systems are generally active healthy people, while low states of the immune system make for patients with unaccountable low energy, liable to all manner of pathologies and symptoms, perhaps veering towards a highly fatigued syndrome.

Seen in this way, provided one can perceive something, at feast, of the naturopathic vision of what makes the human organism ‘lick”, Aloe emerges as a kind of “pick-me-up” tonic. Not a tonic, or semi-panacea, based upon hype and over-imagination, but a “pick-me-up” tonic which has undergone much detailed scientific evaluation. The concept of a ‘Ionic” is an old idea and the term is not much used today. This is because the idea of a medicine which would boost you whatever was wrong, which would build you up generally, has come to be thought of as an out-of-date and out-moded idea. The intricate knowledge about the mode of action of modern drugs, seemed to deny even the possibility that there could be such a substance. However, this particular medical scientist has come to the conclusion that Aloe is, indeed, just this kind of a substance and medicine. And that conclusion is based upon the knowledge of the antiinflammatory, immuno-stimulant and cell growth and replication (healing) activities of Aloe vera, all of which lead to its abilities to cleanse, detoxify, heal and repair. These activities together amount to a revitalizing influence.

5) The Importance of Nutritional Measures to Support Aloe’s Actions

The purpose here is to note the consequences of conclusions from Section 1 of this Newsletter, which indicated clearly that Aloe does not work to any important extent through the provision of nutrients, but rather through furnishing specific stimulants to cellular function. Naturally, this means that, when Aloe is being used, the nutrition of the person remains to be considered as a separate and addition matter. The cellular stimulants provided by Aloe are unlikely to be fully effective if the person’s cells are subject to nutritional deficiency or to out-of-balance nutrition. The diagram in Figure 4 addresses only the immune system and illustrates just how the levels of 16 different nutrients impinge upon 19 different parameters or indices of immune system function. This has been included in order to stress that one just cannot expect the actions of Aloe on the immune system to work so well if these nutrients are not provided at the correct levels and ratios.

THE ACTIONS OF ALOE AT CELLULAR LEVEL AND ITS RELATIONSHIP TO NUTRITION

Above all, Aloe vera acts upon cells within the body, usually by stimulating them into extra activity, such as growth, replication, and secretion. In the case of immune cells it stimulates theengulfing of foreign impurities and the release of special chemical messengers. In a few situationsAloe’s action is to discourage the release of unwanted chemical messengers. The main point here is that Aloeconveys subtle information and encoded instructions for cellular activities of many kinds. It does not heal through Nutrition, although many companies which sell it claim that it does. Therefore, to get the full benefits of Aloe it should be used in conjunction with nutritional supplementation.

1. What Aloe is not – It is not a Nutritional Supplement

Promoters of Aloe products often promote them on the grounds that they are capable of contributing substantially to a person’s nutritional status. This is not true. Typically, Aloe is said to contribute valuable minerals, vitamins and amino acids. Sometimes the essential fatty acids are also mentioned. To begin to understand why this is not valid, it helps to consider the concentration of solids in Aloe vera juices. Aloe vera Gel, compared with most plant juices and extracts, is a very thin fluid containing only a very low concentration of soluble solids. Plant juices and extracts made from forage crops, such as grass or lucerne, normally have a much higher concentration of soluble solids, perhaps in the region of 7 to 10% by weight, compared to the concentration in Aloe vera Gel of only 0.46 to 0.6%. This may be fairly ascribed to the fact that the Aloe vera Gel is a water-storage part of the plant Even Aloe Whole Leaf Extract averaging 1.25% solids, is quite weak in terms of solids, even though it has powerful biomedical properties. If you consume 10ml per day of Aloe Gel at average strength, then you are taking about 0.055g (55mg) Of solids. 50ml (a substantial dose) will give you 0.275g (275mg). With the Aloe Whole Leaf Extract 10ml will give you about 0.125g (125mg) and 50ml will give 0.625g or 625mg. For nutrition to be significant at all in these tiny quantities. the Aloe would have to be very concentrated in respect of some important nutrient or nutrients with very low daily requirement. Therefore, we look briefly below at the principle nutrients that are present in these small amounts of Aloe solids.

Total solids and free sugars

According to researchers Pelley and Wang at the University of Texas Medical Branch, simple sugars are a fairly high proportion among the total solids in the Aloe Gel fluid, i.e. 0.28% by weight, or about half of the total dissolved substances of the fluid. These simple sugars have been analysed as predominately glucose (about 95% of them), with 5% of fructose, which is fruit sugar. Having accounted for 100% of the simple free sugars in this way, there would appear to be little scope for finding any other simple sugars such as mannose, xylose, arabinose, rhamnose or di- or trisaccharides. It is clear that any of these that are present in the free state must be there in only trace concentrations. So far as glucose and fructose are concerned, it would seem that one can virtually forget them as significant contributors to Aloe’s unique bio-medical actions. Glucose is such a common sugar and its properties are so well-known that it is not credible that a 0.28% solution of glucose could have significant effects. For example, an individual consuming 50ml of Gel fluid per day will be consuming only 133mg of glucose and 7mg of fructose from the Aloe source. Compared with, say, the 50g of glucose that is taken for the glucose tolerance test, the amount is clearly quite negligible.

Free form amino acids

Dismissing free sugars as a significant factor, the Gel fluid contains amino acids. Different authors have reported finding them, from 17 to 20 in number, but then plant biochemists would expect almost any plant juice to contain them, for they are, of course, the precursors of plant proteins. One author reports that arginine was the most abundant of them while another that aspartic acid, glutamic acid, serine and histidine were the most abundant. The literature shows up some uncertainty among researchers as to whether any of these amino acids can have specific bio-medical activities ascribed to them. One author considers that they contribute to the wound-healing property of Aloes and another that they contribute to the stimulation of phagocytosis which Aloe produces. The latter property was being ascribed to the two individual amino acids cysteine and proline. The difficulty with these ideas as an approach to explaining the actions of Aloe is that any effect of the amino acids would have to be rather non-specific, and, since virtually all plant extracts contain free amino acids, it is hard to see just how this sort of theory would even begin to explain the individuality of Aloe, and its near-uniqueness of action. Moreover, a great many of our foods contain some free amino acids, and, whether our digestive system is working well or not, some considerable quantities of free amino acids are always being generated in our intestines. True, one cannot reject the amino acid theory out of hand, because there is no doubt that individual free amino acids can have therapeutic effects when given in quantities ranging from 1 g to 6g per day. A daily dietary protein intake, even if it is only 60g per day, quite a low figure, will deliver an average of 3g of each of the 20 principal amino acids that make up proteins. Once again, given that the total solids in a 50ml dose of Aloe vera Gel fluid at a 0.6% concentration would be only 300mg and that any individual free amino acid cannot possibly represent more than a trace percentage of those solids, the amino acid theory comes to look very tenuous, indeed.

Organic acids

The next group of substances we may consider is the organic acids, i.e., acids like lactic, citric, isocitric, malic, succinic etc. According to researchers Pelley and Wang these amount to 0.143% of the Gel fluid, considerably higher than any possible concentration of free amino acids. Nonetheless a 50ml dose of Aloe Gel fluid would only yield just over 70rng of this whole fraction, whic is the sum total of all the organic acids present. Certainly, they are substances not noted for having any very marked physiological effects when taked by mouth.Nutricionists very frequently use mineral citrates as nutricional supplements. In this context some 3000 mg/day of citrate may be given just as a carrier for the mineral being supplemented and the intake of citrate can rise in some instances to 6000mg/day. These levels of intake do not produce any known physiological effects, and, indeed, none would be expected, since the human adult produces and destroys a very large amount of citric acid each day, possibly as much as 1000g per day, a quantity which makes the above administered doses negligible. In this context, any contribution of citric acid to the body via Aloe Gel fluid appears completely negligible. The same is true of the other organic acids named above, because they are all interconverted in sequence.

Minerals in Aloe Gel and Whole Leaf Extracts

Aside from the specific references given above to the salts of calcium and magnesium, the question arises as to whether it is possible that the mineral constituents of Aloe make any significant contribution to Aloe’s bio-medical effects. Again, the concentrations are very low and minerals are so readily available from other sources, especially vegetables, of which one is likely to consume so much more than of any Aloe preparation. The concentration of metal cations (positive ions) in Aloe Gel fluid is given by Pelley and Wang as 0.103%, or just over 50mg in a 50ml dose of Aloe Gel fluid. Bouchey and Gjerstad, in a paper entitled “Chemical Studies of Aloe vera Juice” reported upon the relative levels of the major minerals in the juice.

Using their figures, one can derive the proportions of the 50mg mineral contribution given above. These would be potassium 13.2mg, calcium 9.4mg, and sodium 3mg. These figures compare with likely dietary figures from a good wholefood diet of 6000mg for potassium, 1000mgfor calcium and 500- 1000mg for sodium. Magnesium is only likely to be delivered at about 2 to 4mg per day compared to the intake from a wholefood diet of about 400mg. Even if a concentrated form of Aloe Gel fluid were used, the mineral contributions would remain absolutely minimal, with far cheaper items, like rhubarb and lettuce being far more efficient at supplying them. The mineral contribution from Aloe can safely be disregarded as having any possible bearing at all upon the sources of Aloe´s magic.

Special mineral salts of organic acids

Some of the substances in Aloe claimed by researchers to have physiological actions are mineral salts of organic acids. Some japanese researchers led by Nishioka found stimulant effects from A. vera extracts on the excised heart muscle of laboratory animals and identified the active principle as calcium isocitrate. Also, several Japanese workers have identified magnesium lactate as being one of the substances in Aloe which inhibits gastric secretion, called aloe-ulcin. These results, like some of the others that have been cited above, are really unexpected and need further explanation because of the very low concentrations of these organic salts that could be present in an Aloe Gel fluid and because the compounds mentioned are by no means peculiar to the Aloe plant, being common metabolites throughout the animal and plant worlds. Because of these considerations, it seems really unlikely that either calcium isocitrate or magnesium lactate have any key or central role in creating the special pattern of physiological properties which characteristically belong to the Aloe plant.

Vitamins

In common with all plant juices Aloe vera extracts contain just trace levels of various vitamins. Given the extremely low concentrations and the rather small doses of Aloe vera normally taken, they are most unlikely to make any significant contribution towards human vitamin requirements.

2)So How Exactly does Aloe Act upon Cells?

2a) The Immuno-Stimulant Effects

Issue No 1 gave a clear statement about the effect of Aloe in stimulating the engulfing of foreign impurities by macrophages, the process known as phagocytosis. Issue No 12 explained the actions of the polysaccharide fraction of Aloe and its role in bringing about the immune response. This polysaccharide fraction, which does not often represent much more than 10% of the total solids of Aloe extracts, seems clearly to exert its prime immunostimulant effect at the level of the macrophage. It is almost certain that there are other immuno-stimulatory substances in Aloe in addition to the high molecular weight polysaccharides. One can deduce this from the fact that even Whole Leaf Extracts and Concentrates which have been heavily treated with ceilulase enzyme, in which the high molecular weight polysaccharides have been broken down, possess remarkable immuno-stimulant activity. There are also reports that some anthraquinones (which are concentrated in the Exudate Fraction of Aloe, but which usually survive at very low concentrations in the Gel or the Whole Leaf Extract) possess immunostimulant activity. There is also interesting speculation that the proteoglycan (or glycoprotein) fraction of Aloe vera of molecular weight 10,000 to 50,000 may possess immuno-stimulant activity in the same way as has been clearly demonstrated in the case of Aloe arborescens (“Aloctin A, an Active Substance of Aloe arborescens Miller, as Immunomodulator”, imanishi, K. 1993). Nevertheless, various workers have now demonstrated an effect which can easily be produced with high molecular weight glucomannan from Aloe, which is exerted upon the macrophages. In addition to increasing macrophage activity directly, the macrophages are caused to secrete messenger substances capable of diffusing through tissues to stimulate different activities on the part of other cell types within the immune system.

The three special chemical messengers produced by macrophages when they have been stimulated by glucomannan from Aloe are called “kinins” or “cytokines”, words that signify that their effects have much to do with movement or action. The scientific names of these substances might be off-putting to some, of course. Bear in mind though, that as a user of Aioe one has absolutely no need to memorize any of these details, which are provided here only for reference, and for completeness and accuracy. The same information could be given about them referring to them just as 1,2,3, etc.

Tumour Necrosis Factor α

Has the effect of inducing tumour regression, i.e., making the tumour shrink and also bringing about inflammation. Its role is presumably of great importance in activating immune cells to attack and destroy tumours.

Interleukin 1 β
Activates T Lymphocytes (another important cell type within the immune system). Production of fever and inflammation.

Interleukin 6

Promotes inflammation and activates B Lymphocytes.
The macrophages can also directly stimulate the T lymphocytes to produce two further substances: These are;

Interleukin 2

This stimulates the differentiation ofT and B lymphocytes (i.e. their development from earlier stages in their growth) and also induces ceiï multiplication among the lymphocytes.

Interferon γ

Interferon was much publicised a few years ago as a potential anti-cancer agent, but it never quite fulfilled its early promise in that role, its importance is recognised, however, in the anti-viral applications of Aloe products.

View these cytokines just as a variety of small sized molecules which carry messages. They can be described as “soluble proteins or glycoproteins produced by leucocytes (white cells), and in many cases other cell types, which act as chemical communicators between cells, but not as effector molecules in their own right”. The fact which is of interest here is simply that the activation of different processes and different cell types within the immune system starts with the stimulation of the macrophages. These respond by secreting the three special cytokines listed above. These seem to start a cascade of events whereby additional cell types within the immune system are brought into the fray each to perform their own characteristic functions. Each contributes to the sum total of the immune system’s actions.

Any reader wishing to find out more detail about these important cytokines that are produced in response to Aloe can consult ‘The Cytokine Factsbook” by R. Callard and A. Gearing (1994), published by Academic Press.

2b) The Anti-Inflammatory Effects

These have been discussed, of course, in Issue 2, and the low molecular weight active principles were identified as being (1) sterols (2) anti-histamine (3) salicylates. The enzyme protein bradykininase was also related to inflammation reduction. It is now clear that the glucomannan of Aloe, which is its best identified and best researched active principle, also plays a role in the anti-inflammatory effect. The precise fraction or fractions of the glucomannan which exert this effect have yet to be clearly identified, but it seems clear that some of them at least are present in the middle fraction of molecular size and weight. These fall in between the smaller molecules which have anti-diabetic action and the largest molecules which embody the prime immunostimulant activity. Hence, the anti-inflammatory activity must be ascribed to a whole complex of bio-active molecules. This is very much in accord with Professor Robert Davis’s “Conductor and Orchestra” theory of Aloe’s actions, in which the whole plant or its juice is seen to be substantially greater than just the sum of its parts. (Described in a pamphlet ‘The Conductor – Orchestra Concept of Aloe vera”, published from the Pennsylvania College of Podiatric Medicine).

As we have already considered the nature of anti-inflammatory active principles in Aloe, we may briefly consider here their mode of action at cellular and metabolic level.

The occurrence of inflammation in the first place may be a response to physical injury of tissue, chemical toxic damage to tissue, or cellular damage arising from bacterial toxins. However, the effects of these sources of damage are mediated through quite a number of different chemical messengers. These include;

Prostaglandins of the Series 2 (hormones)
Leukotrienes (cytokine)
Interleukins (cytokine)
Tumour Necrosis Factor (cytokine)
Bradykinin (cytokine)
Histamine (active amine)
“Complement”
Factors
“Permeability” Factors

Once again, there is absolutely no need for the user of Aloe to familiarize him or herself with these names. They are just presented to show the numerous factors involved in the process. In addition to these chemical messengers which tend to induce inflammation, further inflammatory effects are caused by the breakdown products from damaged and dead cells. These includes enzymes released from “lysozomes”, (which are small intracellular bodies) and breakdown products from the nucleic acids of the cell nuclei.

Of the vast number of know anti-inflamatory drugs,most, including aspirin, appear to act by inhibiting the production of the hormones called prostaglandins. They usually seem to inhibit prostaglandin synthesis “across the board”, so that whole group of these hormones is inhibited, not just the inflamatory ones. This is obviously undesirable. Some natural therapeutic agents (such as the pineapple enzyme, bromelain, which is strongly anti-inflamatory) inhibit much more specifically those prostaglandins which are clearly inflammatory. That is a real advantage. This situation does not yet appear to have been worked out for Aloe. We do know, however, that Aloe inhibits pprostaglandin synthesis, as reported by Raine, T., London, M., Goluch, K., Heggers, J., & Robson, M. (1980) , Heggers, J., & Robson, M. 1983 and by Grindlay D and Reynolds, T (1986). One may speculate that the salicylates in Aloe are responsible for this, because this would accord with their close relationship to aspirin.

The presence of bradykininase in Aloe clearly implies that the pro-inflammatory cytokine called bradykinin is reduced by Aloe in this way (Fujita, K., Teradaira, R., & Nagatsu, T. 1976, Yagi, A., Harada, N., Iwadare, S., & Nishioka, 1.1982, and Yagi, A., Harada, N., Shimomura, K., & Nishioka, I., 1986).

Sterols reduce inflammation by reducing the vascular swelling and increased vascular permeability associated with inflammation, and hence they reduce the oedema and swelling of tissues during inflammation. This in turn reduces redness and pain. Furthermore, they inhibit the migration of white blood cells to the site of injury, reduce phagocytosis and the proliferation of blood vessels and of fibroblast cells.Aloe contains the three potent plant sterols,, Lupeol β -Sitoserol and Campesterol, which appear to act in reducing inflammation in a way realy quite similar to the steroid drugs as show in “ Aloe Vera, Hydrocortisone and Sterol influence on Wound Tensile Strenght and Anti-inflammation. Davis R.H. Didonato, J.J. Johnson, & W.S., Steawart, C.B. (1994)

The fourth major way in aloe appears to reduce inflammation is by an anti-histamine effect. This is likely to be archieved by either inhibiting the production of histamine or by activating its removal. Magnesium (even though a dose of Aloe delivers so little of it) has been proposesd as an inhibitor of hisidine decarboxylase, the enzyme which forms histamine from the amino acid histamine. It has also been sugested that magnesium and salicylate might be synergistic (Le that they may produce a larger effect together than the sum otal of their individuals effects). This is as much as we know at present about Aloe´s anti-histamine action.

Also there is no clear published evidence about the mechanism by which either anthraquinones or glucomannan reduce inflammation. Nonetheless, it appears that Aloe may well be so special in its antiinflammatory role simply because of the number and range of the different anti-inflammatory factors which it contains. The different anti-inflammatory factors clearly (from the above) do not work by the same mechanism or upon the same parts of the cell. Rather, many of them work by different cellular mechanisms, or by a different range of mechanisms. This means, that with Aloe, several different parts of the inflammatory mechanisms of the tissues are “calmed down”, each of them by a different component of Aloe’ armoury of at least six anti-inflammatory active principles. Obviously, the resulting antiinflammatory effects often can be greater and more impressive than the results from any single prescription drug which is acting only on one aspect of the inflammatory process.

The effects of Aloe on the actual processes of tissue inflammation may or may not be equal or superior to the effects of steroid drugs. However, in this context the negative effects and side-effects of steroid drugs have to be borne in mind. These drugs not only suppress inflammation but also suppress the healing of wounds and are strongly immuno-suppressive. These are most undesirable effects and represent a very high price to be paid for the reduction in inflammation which is achieved. Professor Davis and his colleagues have shown that, whilst hydrocortisone suppresses inflammation and also suppresses healing, Aloe vera reduced inflammation and at the same time stimulated the healing of wounds | very strongly. This is possible because, whilst the steroids in Aloe vera work quite like hydrocortisone, Aloe
vera also contains strong healing and cell-proliferative effects which more than outweigh the suppressive effects of the Aloe phytosterols. Moreover, the Aloe, as we have seen, also contains very powerful immuno-stimulant substances which do much more than compensate for any from Aloe’s phytosterols, leading to a strongly immuno-stimulant effect overall. Once again, the ways in which these various actions work together seems to confirm strongly the viewpoint that the various active principles of this plant work in a synchronous and co-operative way, hence re-inforcing Professor Davis’s “Conductor – Orchestra” concept. There is absolutely no drug that can do that. With Aloe, indeed, “The Whole” apparently, is worth more than the sum of its parts. This is now more than just a saying – it can be seen
from the scientific and medical evidence.

2c The Healing Effects of Aloe

This special action of Aloe was discussed in detail in Issue 4, which explained the effects upon the cells called fibroblasts, which are involved in forming the new tissues required for the healing of wounds. The beneficial effects were traced once again to the glucomannan, but also to the plant hormones auxin and gibberellin. Obviously, these are the components which have the ability to overcome and to reverse the suppressive effects exerted upon healing by Aloe’s phytosterols. That explanation in Issue 4 contained much of what is known about these particular actions at cellular level.

Most authorities agree that the mechanism of increased wound healing really is still obscure and that what we have is just a set of reasonable theories about it. Whatever the mechanism, it is clear that glucomannan plays an important part and that the effects include wound margin shrinkage and a growth of new tissue called “granulation tissue”. This is accompanied by the spread of new blood vessels through the wound area and there is an increase in synthesis of collagen, the fibrous protein which connective tissues need to give them strength.

It is not entirely clear what molecular size fraction of Aloe polysaccharide is responsible for the healing action. Having identified physiological roles for the smallest and largest sizes, one might well expect to find this activity in the region 50,000 up to one million molecular weight. However, Tizard, I., Busbee, D., Maxwell, B. & Kemp, M.C. “Effects of Acemannan, a Complex Carbohydrate, on Wound Heaiing in Young and Aged Rats” (in “Wounds” Vol 6, No. 6 Nov. – Dec 1994) reported healing activity specifically in the commercial product Acemannan, which contains high molecular weight material. He ascribes this action of an Aloe component to its ability to stimulate macrophages to produce cytokines, in just the same way as the immuno-stimulant action. The cytokines that are relevant to wound healing include some of those listed above under the heading of immuno-stimulation, such as Tumour Necrosis Factor a, Interleukin 1(3, and Interleukin 6. It appears that some of these messengers may be chemical attractants for macrophages and hence may be effective at bringing more macrophages to the site of injury. They also have been found to stimulate fibroblast multiplication. Hence, we have two alternative theories about the multiplication of the all-important fibroblast cells within the injury, one based upon glucomannan stimulating the fibroblasts indirectly via macrophage action (Tizard) and the other (Davis) involving direct stimulation of fibroblast by glucomannan. Since macrophages do produce a specific fibroblast growth factor (FGF), it is inherently likely that macrophages do have some role in the fibroblast response.

Still other factors produced from macrophages induce angiogenesis (the growth of new small blood vessels to supply the wound area). These include Interleukin 8 and another factor with the abbreviated name PDGF (Platelet Derived Growth Factor), which also has the ability to stimulate the growth and division of connective tissue cells.

It therefore seems at this stage of knowledge that there are multiple mechanisms involved in the wound healing response of Aloe.

2d The Digestive Effects of Aloe

The digestive effects of Aloe are among the most important actions of the plant and yet we really have no physiological studies to indicate how these are mediated. It is inherently probable that the gastrointestinal system benefits from both the immuno-stimulant and anti-inflammatory actions. The gut contains an amazing array of immune “lymphoid” tissue. There are major concentrations of this tissue in a few places, such as the so-called “Peyers patches” of the small intestine and the appendix. The latter is illustrated in Figure 2. However, no part of the alimentary system is left unprotected by the immune system and the intestines in particular have small dense areas of lymphoid cells spread through their tissues in an irregular fashion. This is evidence of the intestines being such an important area of direct
contact between the body and its environment that the immune defences have to be well marshalled there. It is inherently likely that the performance and integrity of the gut depend to great degree upon the strength and activity level of these immune defences. This may well be one way in which Aloe aids gastro-intestinal health. The antiinflammatory effect will also be marshalled whenever the early adverse and pathological changes begin in the gut, and Aloe may well enable such adverse changes to be extinguished before they give rise to troubles. However, the work of Dr Bland, mentioned in Issue 3 of these Newsletters, suggests strongly that there may well be another, more direct action of Aloe upon the digestive organs, whereby their vitality is toned up and their secretory functions are normalized. We have no hint as yet of just how these benefits are produced through actions at cellular level.

3) Aloe’s Effects upon Drug Action

A further action of Aloe, though one likely to be of no more than passing interest to Practitioners of Alternative Medicine, is that of potentiating the effects of orthodox drug medicines. This was first demonstrated by Davis RH, Parker WL, Sampson RT & Murdoch DP (1991) in “Aloe Vera as a Biologically Active Vehicle for Hydrocortisone Acetate “ J Am podiatr Med Assoc 81 (1)Since then it has become clear that Aloe can aid in the penetration and delivery of other orthodox drugs and can potentiate them in ways that result in the desired response being obtained with a lower drug dose than would be required ordinarily. Practitioners who do not use drugs will not be impressed af all. However, there may be cases where drug use is inevitable and where it is better to be able to employ the drug at a reduced dose.

4) The Overall Picture of Aloe’s Actions

Diagrammatic Pilot of the Pattern of Aloe´s Actions

We now look at the different actions of Aloe in the form of a diagram which helps to understand the relationships between them. This diagram in Figure 3 summarizes the sequences of events which lead to the three prime actions of Aloe. The hypoglycaemic (antidiabetic effect) is also included within this diagram. The reader is asked to please trace the pathways involved in generating these actions as follows. Much of what has already been discussed is summarized in these paragraphs.

1) Bradykininase, steroids and antiprostaglandin substances in Aloe lead to the overall antiinflammatory effect. As an anti-histamine action by components of Aloe has also been mooted in some literature, that too has been included.

2) The main polysaccharide rich fraction of Aloe, which is a mixture of glucomannans and glycoproteins, stimulates cell activity by interacting with cell-surface receptors as has been explained earlier. This effect influences the cells of the immune system, but specifically, lymphocytes, neutrophils and macrophages. This result, combined with the effects of increased cell numbers, which result from Aloe’s mitogenic (or cell-multiplying) effect, give us the totality of the overall immune response to Aloe. This sequence is followed through in the central horizontal path on the diagram.

3) At the same tin e plant growth factors, named gibbereilins and auxins, together with the mannoserich mannans and glycoproteins stimulate a variety of cell types to divide. It is clear that a number of immune cell types are included within that effect and also the fibroblasts, which give rise to the healing response within damaged tissues. The result of this cell division, of course, is increased cell numbers, within the immune system and also among the fibroblasts. The increased numbers of immune cells make their contribution to the overall immune response ehilst the increases in the numbers of fibroblasts bring about the healing response in damaged tissues. This sequence is followed through in one of the lower
horizontal paths on the diagram.

4) As has been recounted already, the macrophages, upon being stimulated in their activities bymannans and glycoproteins, release two chemical messengers called interleukin-1 and tumour necrosisfactor, and thereby further increasing the division and activity of other cells, including the fibroblasts whichare responsible for healing. This is believed to have the end-result of enhancing the healing effect. This sub-pathway is traceable through the backward-directed arrows in the lower central part of the diagram.

5) As an additional effect, the hypoglycaemic effect has also been included, although its mechanism is less certain. It is worth noting, however, that increasing cell division calls for increasing synthesis of cell constituents to form these new cells. It therefore implies that metabolism is being strongly directed, under the influence of Aloe, to synthetic activity rather than breakdown activity. The synthesis of cell constituents, leading to their accumulation, is known as “anabolism” or an “anabolic effect”. The opposite effect, that of encouraging breakdown of cellular constituents, would be called “catabolic”. It would seem, therefore, that the general tendency of cells acting under the influence of Aloe is towards anabolism. Not only does cell division absolutely require this, but it is also a known metabolic influence of gibberellins to encourage protein synthesis, and hence, encourage the build-up of cellular material. Moreover, the receptor on the fibroblasts which unites with mannan, is one which also accepts the “insulin-like growth factor”. Insulin in an abundantly anabolic hormone, which again, accentuates Aloe’s connection with anabolic, rather than catabolic effects. The inference which may be drawn from this, at least tentatively, is that the general nature of Aloe’s effects are anabolic. This general tendency could well be at the route of the inhibition of gluconeogenesis by Aloe, which has been reported as being the way in which Aloe lowers the blood sugar of hyperglycaemic individuals. This probable mechanism is represented in the bottom right hand part of the diagram.

After these steps have occurred, the prime actions of Aloe represented in the diagram can start to influence medical conditions such as those listed out against the headings of ‘Inflammation’’, “immunostimulant” and “healing action” at the start of this Chapter. Influencing the health status of the patients in these conditions and reducing their symptoms therefore comes at the end of the cascade of events being described.

The Wholistic and Vitalistic Implications of Aloe’s Actions

immunological and pathological terms, in other words, according to the thinking and language of the Medical Sciences. However, Aloe’s virtues appeal to a great many people who do not necessarily subscribe to all the precepts of orthodox medicine. These people are likely to say that they use Aloe “for its cleansing action”, or for its “revitalizing effects”.How is it possible that Aloe, as well as doing all that has been described in therms of medical and cellular effects that have been observed and studied by medical scientist , can also accomplish these less well defined functions that carry weight within Alternative and Complementary Medicine. This author does consider that these things are mutually compatible.

So far as “cleansing” is conserned, this is generally understood to be the process of clearing out both metabolic waste products and enviromental toxins that have entered the body and be taken up by its cells. Toxins produced by intestinal bacteria and then absorbed, also have a part to play. The hypothesis that lies behind the concept of cleansing is, briefly, as follows. Innaturopathicterms, the factor which mos compromisesbodily health is the accumulation of toxic waste and poisons in the living cell. The mechanism by which these substances produced effects could never be specified by the early naturopaths. It is now clear, however, that what lay at the foundation of their mental concepts about this was the inhibition of cell enzymes, especially those which break down foods to yield energy, those which synthesise proteins, including the enzymes themselves, those concerned in the synthesis and maintenance of the nucleic acids, and those concerned with the formation and maintenance of the external and internal cellular membranes. These are the parts of the living processes of the cell which are the most vulnerable to damage by toxins. All such damage contributes to making the cell inefficient and ineffective where the cell was vital and active before. Cells become moribund and die under the influence of toxins. The event of cel! death is preceded by a time when the cell is hypoactive (i.e. underactive) on account of its load of toxins. Most particularly the energy-generating mechanisms of the cell are damaged or hindered. The cell has less energy to work with. Its processes are slowed, its respiration, its synthesis of proteins, its ability to repair itself and replace its parts, and, most important, its ability to maintain its own internal environment, with the correct concentrations of sodium and potassium, calcium and magnesium.These are the processes of chronicity. It is a process which leads the body towards lowered vitality and activity.

In the naturopathic philosophy, onward progression of toxicity and of the chronic condition is a general disease-encouraging process. Some types of toxin affect one or more tissues or organs preferentially. In other cases the toxic effect is non-especific as to tissue type. The body organ or system fails and hence what disease develops then depends upon constitutional and inherited factors that are peculiar to each individual. It does mean, however, that it is generally true that the chronic diseases can be avoided by avoiding getting into toxic and chronic conditions.

Aloe vera, as we have seen, activates the immune cells, and in particular, it activats the scavening macrophages and neutrophils which carry out clean-up operations. This role the immune system makes it a great detoxifier. Those of them which operate within the confines of the lymphatic system, in the lymph glands, actually engage’ in cleaning up the lymph as it flows from the tissue drainage areas towards reentry into the blood-stream.

Aloe, as we have seen, also activates cells into a growth and replication phase, accompanied by much protein synthesis and the general build-up of tissue constituents. This is what has been termed “anabolism”. Cells in this positively activated, constructive and reproductive phase have increased activity and this is emphasised by their increased oxygen consumption. Such activated cells have heightened metabolism and have moved far from the chronic state. It is therefore a fair interpretation of the actions of Aloe that it moves cells away from hypo-active and therefore chronic conditions towards the highly active states in which detoxification occurs readily due to the cell’s favourable energy supply. Returning again for a moment to the condition of the immune system, it is a matter of clinical observation that patients with good and active immune systems are generally active healthy people, while low states of the immune system make for patients with unaccountable low energy, liable to all manner of pathologies and symptoms, perhaps veering towards a highly fatigued syndrome.

Seen in this way, provided one can perceive something, at feast, of the naturopathic vision of what makes the human organism ‘lick”, Aloe emerges as a kind of “pick-me-up” tonic. Not a tonic, or semi-panacea, based upon hype and over-imagination, but a “pick-me-up” tonic which has undergone much detailed scientific evaluation. The concept of a ‘Ionic” is an old idea and the term is not much used today. This is because the idea of a medicine which would boost you whatever was wrong, which would build you up generally, has come to be thought of as an out-of-date and out-moded idea. The intricate knowledge about the mode of action of modern drugs, seemed to deny even the possibility that there could be such a substance. However, this particular medical scientist has come to the conclusion that Aloe is, indeed, just this kind of a substance and medicine. And that conclusion is based upon the knowledge of the antiinflammatory, immuno-stimulant and cell growth and replication (healing) activities of Aloe vera, all of which lead to its abilities to cleanse, detoxify, heal and repair. These activities together amount to a revitalizing influence.

5) The Importance of Nutritional Measures to Support Aloe’s Actions

The purpose here is to note the consequences of conclusions from Section 1 of this Newsletter, which indicated clearly that Aloe does not work to any important extent through the provision of nutrients, but rather through furnishing specific stimulants to cellular function. Naturally, this means that, when Aloe is being used, the nutrition of the person remains to be considered as a separate and addition matter. The cellular stimulants provided by Aloe are unlikely to be fully effective if the person’s cells are subject to nutritional deficiency or to out-of-balance nutrition. The diagram in Figure 4 addresses only the immune system and illustrates just how the levels of 16 different nutrients impinge upon 19 different parameters or indices of immune system function. This has been included in order to stress that one just cannot expect the actions of Aloe on the immune system to work so well if these nutrients are not provided at the correct levels and ratios.