How can aspirin help to cure cancer?(1) This question is a consequence of long out-dated dogma of the medical establishment. The truth that puts a lie to this worn-out dogma has been available in the public domain for more than ten years.(2) The truth has been ignored, inadvertently or deliberately, by the medical establishment and by nutrition academia, which is medicine’s principal authority for nutritional ignorance and pseudoscience.
The work of Serhan and colleagues(3) introduced a whole new area of research that helped expose the inadequacies of the establishment’s dietary guidelines for Americans. Even some of the more progressive diet groups, such as the Paleo-fitness folk, who recognize and accept the role of an evolutionary diet as a critical factor in the making of Man, cannot seem to see beyond “sugar” as the only dietary component of significance.
Had the medical and nutrition establishments not been forever mired in their own esoteric science and research, they would have been aware much earlier of new ideas in relevant fields of science. The nutritional importance of the essential fatty acids had been well established and accepted prior to World War II, but the significance of the metabolism of their end point eicosanoids, including the function of aspirin, were of little interest outside the laboratories of Serhan and colleagues. This new science was subsequently labeled lipidomics.
Why Now a Defense of Lipidomics?
In the past two decades there have been references to eicosanoids in many public documents that have had sufficient readership to reach the eyes and ears of medical and nutritional science. The intent of this post is twofold. One aim is to provide excerpts from a few of these many documents to show that there is no valid excuse for ignorance of the existence and significance of lipidomic science.
The second purpose is to fight for the conviction that acceptance and implementation of the science of lipidomics is essential if a complete understanding of the relationship between diet and human health/disease is to be achieved. For example, the causes and consequence of obesity have been subjects of debate ever since obesity appeared on the scene in alarming numbers after World War II.
The pioneers in restricted-carbohydrate nutrition, Atkins clinically and the Eades clinically and biochemically, proved the relationship between excess carbohydrate intake and excess body fat. Low-carbohydrate diets resulted in weight loss. But the few exceptions to weigh loss that occasionally occur in this relationship utterly confound nutritionists. Thus, the debate goes on. Nutritionists have no answer; however, consider the effect of a dietary intake of excess linoleic acid, which is the omega-6 fatty acid that is one of the two parent compounds that give rise to lipidomic science.
Dietary intake of linoleic acid (LNA, 18:2n-6) has increased dramatically during the 20th century and is associated with greater prevalence of obesity. The endocannabinoid system is involved in regulation of energy balance and a sustained hyperactivity of the endocannabinoid system may contribute to obesity.(4)
This is just one of many examples of solutions to significant nutrition problems that cannot be found in the medical or nutrition literature but can be found in lipidomics. It is unfortunate that when the answer to a problem exists in a discipline that is unacknowledged or unaccepted, the answer is nonexistent.
Excerpts from Books Blogs and Scientific Journals
Enter the Zone
We first learned of the existence of this amazing new science of lipidomics in 1995 from the very popular and widely read diet book Enter the Zone by Barry Sears.(5) To our knowledge, it was Sears who introduced the term eicosanoid and the fatty acid arachidonic acid to the nutrition segment of the reading public. Sears’ brief but intriguing description of the behavior these newly discovered cellular “hormones” whetted our interest to learn more about their potential role in human health. Our interest still persists, but that of medical and nutritional sciences were not even aroused.
Protein Power Lifeplan
The promise of this new science did not escape the notice Drs. Michael and Mary Dan Eades. In 2000, they published Protein Power Lifeplan(6) that included an informative chapter on the little known but critically important subject of the essential fatty acids. That the chapter was visionary is shown by the following excerpt:
Before we get into how you can take EPA[eicosapentaenoic acid] and DHA directly, let’s take a look at why it is important for you to get them in the first place….The omega-3 and omega-6 fats have much different functions…only these fats can be transformed into eicosanoids. …In short, eicosanoids control just about any physiological function you want to talk about. … As long as these two groups of eicosanoids are in balance, the system hums along beautifully. …Countless studies have correlated an increased level of omega-6 with increased rates of heart disease, insulin resistance, cancer, diabetes and the rest of the diseases that go along with getting older (6, p. 71).
In 2002, another nutrition book written for a lay audience was published(7). It included, to the extent of what was generally known about them, a discussion of the eicosanoids. It presented figures detailing the metabolic pathways of the eicosanoids, including the metabolism of arachidonic acid via the COX-2 and the lipoxygenase pathways. The following paragraph predicts type-2 diabetes:
Excess dietary sugar/starch may actually be more harmful than implied by the information above. Note that the eicosanoids produced from arachidonic acid include the LT-4 leukotrienes. One laboratory study has shown that a leukotriene in the LT-4 series (see Figure 2-5) stimulates insulin release (26, p.193). If this laboratory study is correct, a sugar/starch diet may initiate the following vicious cycle: 1.) Insulin, secreted in response to a high sugar/starch intake, stimulates the production of LT-4 leukotrienes. 2.) These LT-4 leukotrienes stimulate the release of more insulin. 3.) This insulin stimulates more leukotrienes. Such a biochemical vicious cycle may help to explain why diets that are constantly high in sugar/starch are particularly harmful (7, p. 48).
Needless to say, medical and nutritional science remained unresponsive, despite the popularity, reputation, and paleopathological/biochemical acumen of the Eades. Despite failure to enlighten the medical and nutrition communities of the exciting findings in the new science of lipidomics, attempts to do so continue to the present.
Serhan’s Research and the Origin of Aspirin’s Role
In 2013, a more detailed review directed to a lay audience of the research of Serhan and colleagues was published in the second edition of the 2002 book, Modern Nutritional Diseases.(8) The claim that aspirin cures cancer, as decried in the title of this post, had its origins in the research of Serhan and co-investigators who discovered the biochemistry of aspirin’s analgesic effect. The NSAID industry, which was born to compete with aspirin, was founded on the assumption that aspirin’s effect was due to inhibition of the COX-2 enzyme. Serhan discovered that aspirin does not inhibit COX-2 enzyme, but rather acetylates its active sites and forces it to convert arachidonic acid to anti-inflammatory lipid mediators.(8, p. 101)
Thus, aspirin has been found to be important in a fundamental role in modifying inflammatory eicosanoid pathways. Perhaps of even greater consequence for the health and well being of present and future generations are the more recent discoveries of the hitherto unsuspected role of aspirin in resolution (the healing process) and the unanticipated existence of whole new classes of aspirin-triggered anti-inflammatory eicosanoids that have been uncovered by the research into aspirin’s mechanism of action.(8, p, 177ff )
This profound revelation has not yet been recognized by main stream medicine. It is surprising that publication in the scientific literature of the significant role aspirin plays in the biochemistry of lipid mediators has had no impact on the lack of acceptance of aspirin by the medical community. If it had, the question of how can aspirin help to cure cancer would be obvious.
Since 2012, occasional blogs have been written for Ketopia.com when the opportunity to discuss some aspect of lipidomic science presented itself. The following excerpts are taken from blogs that were prepared with the hope that an awareness of the existence of lipidomics and the controls it exerts on all aspects of human physiology and biochemistry would show medical and nutritional sciences that lipidomics has the only answers for some of their most perplexing problems.
When suffering chronic inflammation, the body cannot heal itself. Hence, in the process of trying to survive, it forms scar tissue. We know what scar tissue looks like in skin. However, all scar tissue is not the same. In blood vessels, it is artery-clogging atherosclerosis. In brain, it is the odd tissue seen in Alzheimer’s disease. In the mouth it is inflammatory gum disease. In arthritic joints its boney deformities. In summary, good health depends on a diet that restricts sugar, starch, and vegetable oils and includes ample amounts of fish oil, animal protein, and animal fats.
The research of Serhan and colleagues in the biochemistry of the lipid mediator endpoints of polyunsaturated fatty acids has demonstrated that eicosanoids regulate inflammation and that resolution of disease is not automatic. Resolution requires dietary omega-3 and omega-6 fatty acids, namely eicosapentaenoic (EPA), docosahexaenoic (DHA), and gamma linolenic (GLA) acids. Without control of inflammation and active resolution, the benefits of ketogenic nutrition could be limited or negated.
Lipidomics explains the very complex biochemistry and functions of EFAs and their eicosanoids-docosanoids system. Eicosanoids and docosanoids, also called lipid mediators, constantly monitor and adjust internal functions to maintain normal bodily stability (homeostasis). They also maintain physiological stability by controlling a large number of body functions. Some examples are regulation of blood pressure, gastric mucosal secretion, and gestation and parturition in pregnancy. The eicosanoid control system governs the biochemistry by which health or disease is determined. Lipid mediator imbalance caused by dietary excesses of omega-6 EFAs is involved in the development of essentially all chronic inflammatory diseases.
Lipidomics discovered the marvelous self-healing system with which man evolved from research on chronic inflammatory diseases. Lipidomic study of inflammatory processes revealed countless very complex and never-before-known biochemicals synthesized from EFAs that eventually could only be explained by the prehistoric self-healing system.
The biochemical mechanisms for prevention and treatment of chronic inflammatory diseases are extremely complex and difficult for all but scientists working in the field to comprehend. However, in layman’s words, it is known that the major cause of chronic inflammation that leads to chronic disease is primarily nutritional. In simplest terms, inflammation is the result of a dietary imbalance of EFAs and their lipid mediators. An existing chronic inflammatory disease will progress unabated until the contributory nutritional failing is remedied. It is not until the body is provided with ample dietary EPA and DHA, the lipid mediators described above, inflammation will begin to diminish and healing will commence. These discoveries are tremendously important because they describe the nutritional need for these essential fatty acids and explain the biochemical processes that end inflammation, initiate healing, protect involved tissues, control pain, and return damaged tissues to homeostasis.
The second truth of optimum human nutrition says that the essential fatty acid component of the diet must be balanced. This very simple condition is probably perplexing to most people in the nutrition community. It is a relatively new concept first hinted at in 1929 when the Drs. Burr proposed that one or more of the polyunsaturated fatty acids were essential FAs. Note that this truth requires “balance” but does not specify “in what proportion or direction!
Progress in study of the EFAs was hampered for decades because of the complexity of the biochemicals involved and the inability of organic chemistry of the time to separate and identify long-chain isomers of polyunsaturated organic acids. When it became possible to determine EFA structures, it was found there were two families of EFAs instead of one; one family with its terminal double bond at the omega-6 carbon (labeled bad) and the other with its terminal double bond at the omega-3 (labeled good).
EFAs have lived a dual existence ever since. Omega-6 and omega-3 fatty acids became the province of nutritional scientists; their eicosanoid and docosanoid lipid mediator endpoints became the province of the science of lipidomics. Before the second truth of optimum human nutrition can ever be understood or accepted as law, these two disciplines must unite.
A very important benefit of aspirin is the fact that arachidonic acid is disposed of when it is converted the prostaglandin 15R-HETE; arachidonic acid is no longer available as a substrate for inflammatory eicosanoids. This is an important difference between aspirin and NSAIDS in their interaction with the COX-2 enzyme. NSAIDS do not eliminate arachidonic acid but merely prevent it from being metabolized by the COX enzymes to inflammatory, pain producing eicosanoids. This has positive, immediate pain-relieving effects; however, the unused arachidonic acid is diverted to the 5-lipoxygenase enzyme where it is converted to inflammatory leukotrienes that do damage elsewhere in the body. Hence, NSAIDs have the potential for adverse effects not seen with aspirin.
Lipidomics in Action
Sometime in 1999, DH, a 78-year old gentleman who lived in a suburb of Reno, Nevada, was found to have lung cancer of sufficient severity that he was told he had three to six month to live. Because he was reluctant to undergo the stresses of radiation or chemotherapy in light of such a bleak outlook, he decided to seek the advice of a friend and neighbor who happened to be a biochemist in the UNR College of Agriculture. DH knew that his friend, Professor Ron Pardini, had been actively engaged for many years in studying the use of omega-3 fatty acids in suppressing cancer growth rate.
After considerable discussion and planning with DH’s oncologist and physicians from the UNR School of Medicine, Professor Pardini began omega-3 fatty acid treatment of DH (15). Within one year, 90-percent of DH’s lung cancer was gone. To this day in September of 2015, DH’s lungs are cancer free, and he is still an active member of the community.
Dr. Pardini explained to inquiries from the local press that omega-3 fatty acids in DH’s diet were able to suppress the cancer’s growth, but he cautioned the public that it is important to remember it is just a one-patient study, which does not apply to all lung cancer patients. A complete review of the DH case directed to a scientific audience appeared in Chemico-Biological Interactions in 2006 (16).
- Claria J, Serhan CN. Aspirin triggers previously undescribed bioactive eicosanoids by human endo-thelial cell-leukocyte interactions. Proceedings, National Academy of Sciences. 1995; 92(21): 9475-9.
- Serhan CN, Chiang N. Endogenous pro-resolving and anti-inflammatory lipid mediators. British Journal Pharmacology. 2008; 153: S200-S215.
- Alheim AR, et al. Dietary linoleic acid elevates the endocannabinoids 2-ag and anandamide and promotes weight gain in mice fed a low fat diet. Lipids. 2014; 49:59–69
- Sears B. Enter the Zone. New York, NY: Regan Books, HarperCollins Publishers, 1995.
- Eades MR, Eades MD. The Protein Power Lifeplan. New York, NY: Hachette Book G4roup, 2000.
- Ottoboni A, Ottoboni F. The Modern Nutritional Diseases: and How to Prevent Them. Fernley, NV: Vincente Books, 2002.
- Ottoboni A, Ottoboni F. The Modern Nutritional Diseases: and How to Prevent Them, 2nd Edition. Fernley, NV: Vincente Books, 2013.
- Pardini RS, et al. Nutritional Intervention With Omega-3 Fatty Acids in a Case of Malignant Fibrous Histiocytoma of the Lungs. Nutrition and Cancer. 2005; 52(2): 121–129. http://www.erbeofficinali.org/dati/nacci/studi/Omega%203%20efficaci%20contro%20i%20tumori.pdf
- Pardini RS. Nutritional intervention with omega-3 fatty acids enhances tumor response to anti-neo-plastic agents. Mini-review. Chemico-Biological Interactions. 2006; 162: 89–105. http://naes.agnt.unr.edu/PMS/Pubs/20_2008_06.pdf