Here’s a good study on Echinacea that I never run across before. I specifically like how it addresses some of the medical myths that exist around it.
Echinacea has been viewed as an immunoenhancing herb since it became commercially available several years ago. Indeed, its medicinal significance is responsible for billions of dollars in worldwide sales annually. Unfortunately, most of the ‘evidence’ for the purported medicinal efficacy of Echinaceahas been anecdotal and, moreover, to this day, there is no formal proof on how to achieve the best results—whether it should be consumed daily throughout life as a prophylactic; consumed by either young or old; or consumed after diseases, such as cancer, have taken hold. Our work over the past 5 years has led to conclusive answers to some of these questions, at least in mice. Our results have shown that daily consumption of Echinacea is indeed prophylactic, extends the life span of aging mice, significantly abates leukemia and extends the life span of leukemic mice. Given that humans are 97% genetically common with mice and that virtually all our basic physiology is identical, it is neither unjustified to extrapolate these observations to humans nor would it be an arduous task to perform many of these studies in humans, thus establishing viable scientific evidence replacing the anecdotal.
Natural Killer Cells and Echinacea: a Harmonious Duo
The herb, Echinacea, after making its debut on the world’s commercial markets more than a decade ago, has become one of the top-selling herbs of all time. Many of its ingredients are powerful immune system stimulators. Its contents include high molecular weight polysaccharides, essential oils, alkylamides such as echinacein, isobutylamides such as pentadecadienes and hexadecadienes, polyacetylene, tannins, inulin, heteroxylan, flavonoids and vitamin C. Indeed, the biochemistry and content definition of Echinacea and most other herbs has taken place decades before the medicinal value of the phytochemicals they contain ever merited investigation. Some of the contents of Echinacea are natural killer (NK) cell stimulants while others (the alkylamides) inhibit the endogenous suppressors of NK cells, i.e. the prostaglandins. NK cells are the first line of defense in cancer immunosurveillance, and consequently any agent that will either stimulate these fundamental cells or remove any negative influence on them would be clearly of medicinal value. In spite of the manifold functions of the prostaglandins in vivo, it is clear that at least one member of the prostaglandin family is detrimental to NK cells. The alkamide family of compounds within Echinacea inhibits the production of 5-lipoxygenase and cyclooxygenase, which are enzymes needed for the production of prostaglandins (1,2). Thus, reducing or eliminating this negative influence should result in an absolute and functional increase in NK cells (Fig. 1). Indeed, this is what we found some years ago when the drug indomethacin, an inhibitor of these key enzymes in prostaglandin formation, was administered in vivo to leukemic mice. This drug in vivo resulted in statistically significant increases in NK cell numbers and function in leukemic mice (3,4). Unfortunately, indomethacin, as with most exogenously administered drugs/factors, is beset with significant undesirable side effects that necessarily restrict its long-term use.
Furthermore, there is considerable evidence suggesting that other phytochemicals in Echinacea might have the capacity to reduce tumors and virus infections (5–10). Among the polysaccharides contained within Echinacea, the complex carbohydrate group known as the arabinogalactans are particularly significant (5,11,12). Macrophages upon stimulation by arabinogalactans (Fig. 1) release, in turn, a host of NK cell stimulants (11,13–16).
Consequently, any agent that contains these two valuable compounds, both so beneficial to those cells acting at the first line of defense, i.e. the NK cells, is worthy of investigation for its prophylactic potential and its therapeutic value. It was against this background, i.e. the medicinal potential of Echinacea in NK cell enhancement, that we undertook an in-depth in vivo study of this herb in (i) aged mice and (ii) mice afflicted with leukemia, under controlled laboratory conditions.
Virtually all that was known about the medicinal potential of Echinacea had been established in vitro. Our first study, in contrast, was conducted in vivo ∼5 years ago, and at that time we investigated the effect on hemopoietic and immune cells of daily dietary intake of this herb for 2 weeks (17). After 2 weeks, we analyzed quantitatively the absolute changes in all the hemopoietic and immune cells in both the spleen and the bone marrow, the latter being the organ of de novo generation of all hemopoietic and immune cells. The spleen, on the other hand, is a major repository for all these cells since this organ is on the blood circulatory highway. In the spleen there are cells that reside and function therein, i.e. the cells mediating specific (adaptive) immunity (T and B lymhocytes), as well as NK cells and monocytes—both types being responsible for non-specific, spontaneous and non-adaptive immunity. Other cells involved in the disease defense process, i.e. the mature and maturing cells of the granulocyte lineages (eosinophils, neutrophils and basophils) also either function in the spleen or pass through it en routeelsewhere.
In our analysis of the effect of Echinacea on the above-mentioned cells, everything was standardized. The mice were inbred and of identical age, weight and gender (male). Moreover, housing conditions were identical between cages of mice consuming Echinacea and those consuming untreated diet. The quantity and quality of food and water were also standardized among all cages—those receiving the herb in the diet and those not given the herb (controls).
It is obviously of fundamental importance that Echinacea itself, as with any agent given either prophylactically or therapeutically, is not deleterious to the host. In the case of Echinacea, there appears to be no in vivo toxic level, i.e. overdose level, as defined by several assays and criteria (6,18,19). The immunostimulating effects of Echinacea in vivo are exclusive to cells mediating spontaneous immunity and their accessory cells, i.e. NK cells and monocytes (17). While Echinacea appears to be tailor-made for its highly positive influences on this arm of the immune system, there are instances, in vivo, where use of this herb may be contraindicated. For example, individuals demonstrating allergy to members of the Family Asteraceae, to which Echinacea belongs, would clearly be ill-advised to consume this herb for any reason (20,21). Moreover, there is very little available information concerning the potential for detrimental interactions of Echinacea with either other herbs or pharmaceuticals (22). Another problem pertains to the choice of the most effective source of Echinacea as NK stimulant—not an insignificant problem since there is extremely wide variation in the quality of Echinaceas from assorted commercial sources. For our experiments, we chose a product from a commercial supplier, which we proved was consistent in quality and NK stimulating potency, and revealed in dose–response analyses, a progressive increment in NK cell numbers up to a maximum (plateau) beyond which no further increase in NK cells occurred. It was this dosage that we have used throughout our experiments to date, including those reported in this review.
Should Echinacea be Taken When Healthy?
When healthy young adult mice consumed Echinacea daily in their diet for 7 days, we found significantly more NK cells, identified by our standard immunoperoxidase labeling methods, in their bone marrow than in the bone marrow of mice consuming untreated diet (P < 0.01), while the spleens of mice consuming Echinacea had 25% more NK cells, which is a clear elevation in number although not yet statistically significant (17). By 2 weeks, however, those mice consuming the herb had significantly more NK cells in their spleens and bone marrow (P < 0.01). The early (7 days) elevation in absolute numbers of NK cells in the bone marrow necessarily indicated that actual generation of new NK cells was underway in that organ under the influence of Echinacea. The 25% increment in the spleen simply reflected the increased new NK cell production, since it is well established that the spleen is major site to which virtually all newborn, bone marrow-derived NK cells unidirectionally migrate (via the blood). NK cells do not recirculate back to the bone marrow (23–25). However, during 2 weeks of dailyEchinacea exposure, the elevating levels of new NK cell production by the bone marrow resulted in a supernormal export of these additional NK cells to the spleen, such that there was indeed a statistically significant increase in the numbers of NK cells in the spleen by 2 weeks as well.
Also of considerable interest was the observation that the ‘helper’, or accessory, cells for NK cells, i.e. the monocytes, were ∼25% more numerous in both the bone marrow and the spleen of mice consuming the herb for 7 days, and were statistically more numerous in both organs (P < 0.01) after 14 days of the dietary herb (17). To our surprise, mature granulocytes and their precursors, as well as all other lymphocytes (T and B), and the red blood cell precursors remained steadfastly at control levels (mice consuming untreated diet) in both the spleen and the bone marrow, irrespective of whether mice had consumed Echinacea for 7 days or 14 days. Moreover, we have consistently shown in all our previous studies that all mice on Echinacea-containing diets were clinically no different from littermates and cage mates consuming untreated chow, with respect to body weight, coat texture and level of activity. Our administration to mice of daily dietary doses o