Gar Hildenbrand
Gerson Research Organization

The Lede: We were wrong about coffee enemas and detoxification.

For decades, we thought coffee enemas were only about detoxification, and that somehow detoxification translated into the regressions and remissions of cancer observed over decades by practitioners in multiple licensed facilities.¹ This paper will look at recent developments in coffee science and molecular biology in order introduce the reader to a world beyond the concept of detoxification.

While I was the executive director of the Gerson Institute (1986-1993), we made a sustained effort to publish our ongoing reinterpretations of Gerson’s therapy in the context of the everemerging sciences of immunology and nutrition. New findings on coffee in the early 1980s had identified mechanisms that were unimaginable in Gerson’s time. In 1982, Lee Wattenberg, Luke Lam, and Velta Sparnins² introduced the world to cafestol and kahweol palmitate, diterpenes unique to coffee that demonstrated anticancer properties. At that time, the most remarkable finding in mice was the ability of these alcohol esters to stimulate massive overexpression of glutathione-S-transferase (GST) in the liver and small bowel wall. This finding was repeatedly associated with tumor prevention in animal models challenged with potent carcinogens. Because GST promotes the binding to glutathione (GSH) and excretion in bile of a vast variety of electrophiles, Wattenberg et al assumed that the anticancer effect of cafestol and kahweol was largely due to this enhanced detoxification enzyme.²

Today, both cafestol and kahweol remain widely appreciated as inducers of glutathione-Stransferase (GST), but the importance to cancer of enhanced GST is complex and tissue-specific. Listowsky³ and colleagues demonstrated a wide variety of GST subunits distributed through various tissues, suggesting a similarly wide variety of detoxification and metabolic pathways from tissue to tissue. In their recent review of GST in cancer, Singh and Reindl⁴ catalogued the cancers in which overexpression of GST is negatively associated with survival, including renal cell, gastric, endometrial, pancreatic, melanoma, glioma, urothelial, ovarian, breast, and lung.

Wattenberg’s concept of detoxification dominated coffee science and its research assumptions for decades. Fortunately, the introduction of, and ready access to, efficient and affordable sequencing technologies has allowed researchers to generate sufficient molecular biological data to overshadow and contextualize the concept of detoxification. In its better defined and more narrow form, the concept of detoxification no longer has to account for the pronounced anticancer effects of coffee, which can now be understood to be the work of multiple genes involved in anti-proliferation, anti-migration, apoptosis, anti-angiogenesis, anti-inflammation, etc.; nor does it have to account for the remarkable ability of coffee enemas to manage pain.

It’s Not Detoxification, It’s Danger

Since the introduction of Matzinger’s danger model,⁵ we have come to understand that the innate and adaptive immune systems simply do not see established cancers as dangerous⁶… not even in patients with clean, well-nourished (detoxified) tissues and blood. On the contrary, host cells (predominantly macrophages) cooperate with and nourish tumors; meanwhile, lymphocytes treat tumors like any other rapidly replicating tissue, bypassing them without interaction.

The immune system appears to have only two big, evolutionarily conserved behaviors, 1) response to pathogenic microbes, and 2) response to tissue damage and death. There is no evolutionarily conserved immune response against established tumors. In order to attract the attention of the immune system and program it to clear cancer, tumors have to be wounded (or one might point out, they could also be injected with pathogenic microbes after the manner of William B. Coley).⁷

Nothing in Gerson’s therapy has been historically regarded as cytotoxic or capable of wounding tumors. And yet, Gerson’s therapy has been observed to cure many cases of advanced cancer documented in clinical detail,^{8, 9} and it is impossible to justify dismissing those cases. We are obliged, instead, to practice a sort of empirical reverse-translation inquiry, starting with the unexpected, unexplained improvement or cure of patients, and looking outward and backward into the literature for any possible contributory factors. What in Gerson’s therapy could possibly have wounded tumors repeatedly? Such repetition is essential to acquire the substantial adaptive immune memory necessary for durable remission.

According to the danger model, antitumor immunities are triggered by danger signals emanating from damaged tumors that have disturbed, dead, or dying cells. Antitumor immune effector responses are brief, only about two weeks long, so they have to be triggered repeatedly and frequently. What in Gerson’s treatment might frequently damage tumors enough to generate danger signals that could lead to repeated antigen-presentation and subsequent effector responses capable of clearing tumors?

Rethinking Rationales for Coffee Enemas

The answer may be, at least in part, coffee itself, although not at all for the reasons Gerson believed. When he systematized the use of coffee enemas as part of his cancer therapy, Gerson conceived of them as supporting liver and kidney function. Gerson never suggested that coffee enemas had any direct anticancer effects, rather that they could detoxify the metabolic byproducts of tumor metabolism and degradation. Gerson emphasized detoxification as the primary mechanism of coffee enemas and pain management as their primary clinical effect.

Pain and COX-2

Parenthetically, on the subject of pain management, Kim and Jeong¹⁰ demonstrated that both kahweol and cafestol powerfully inhibit COX-2 at remarkably low levels, kahweol at 10 μM and cafestol at 20 μM. These diterpene levels are clearly achieved by coffee enemas (see “How much cafestol and kahweol are in Gerson’s coffee enemas?” below). Although detoxification, per se, could logically account for at least part of the pain control of coffee enemas, it is clear that their robust inhibition of COX-2 is contributory.

Inflammation

Gerson believed that selective nutrition and aggressive detoxification could unencumber innate anticancer defenses that he believed led directly to his clinically documented tumor regressions, which were in some instances complete and durable.

Gerson’s views were not dissimilar from the current prevailing belief that cancer cells have to be killed:¹¹ “… cancer cells cannot be stimulated or forced to change their abnormal functions back to normal ones. There is no other way but to kill these cells, to dissolve and absorb them.” And he believed that measures to enhance host systemic inflammability could lead to tumor death caused by inflammation per se, “I believe the surest way to achieve this end is to restore to the body its ability to produce non-bacterial inflammatory reactions.”¹¹ This view is only partially correct.

In human research, the effects of inflammation-inducing cytokines like interleukin-2 and interferon have not borne out Gerson’s belief that inflammation alone could regress cancer. On the other hand, it is now accepted that the immune system can be supported and directed in its response to cancer, and that an anticancer inflammatory reaction is triggered in the vast majority of conventional oncology protocols by damage to the tumor.

Although Gerson was convinced that coffee enemas were only detoxifying his patients, modern research of the last several decades strongly suggests that his sustained application of frequent coffee enemas may have had direct antitumor effects.

Can Gerson’s Coffee Enemas Kill Cancer?

Can Gerson’s coffee enemas kill cancer? I pose this provocative question not only to capture the gentle reader’s attention but to introduce exciting contemporary research that elucidates multiple newly identified anticancer roles for coffee and its key components.

Waseem El-Huineidi and Salma Eldesouki of the University of Sharjah provided detailed documentation of the remarkable dose-related anticancer effects induced by coffee’s unique unsaponifiable esters, cafestol and kahweol. According to these authors,¹² “The two diterpenes have a promising potential to revolutionize the field of cancer treatment.” They list solidly documented anticancer effects of these diterpenes as follows:
Kahweol

• Apoptosis induction (including caspase-3-mediated, STAT3-mediated, TRAIL-mediated, p53-independent, ER-stress-mediated)
• DNA fragmentation
• Proliferation inhibition (including PMA-mediated)
• Migration inhibition (including PMA-mediated)
• Invasion inhibition (including PMA-mediated)
• Matrix remodeling inhibition
• Cytotoxicity (including H2O2-mediated)
• Tumor growth inhibition in vivo

Cafestol

• Mitochondrial damage
• Apoptosis induction (including AVT-737-mediated in vivo)
• Cytolysis
• Radiosensitization (Kotowski,¹³ in vitro)
• Synergy with anticancer drugs (Woo,¹⁴ Lima,¹⁵Min¹⁶)

Kahweol and Cafestol Combined

• Migration inhibition
• Proliferation inhibition
• Epithelial-mesenchymal transition inhibition
• Apoptosis induction
• Organelle ROS inhibition
• Clonogenic potential inhibition.

Synergy of Coffee Diterpenes Cafestol and Kahweol with Existing Anticancer Drugs

I sat recently at a tumor board where an oncologist forcefully asserted that coffee enemas given simultaneously with chemotherapy would detoxify the drugs before they worked. Today, this assumption is surprisingly persistent among some practitioners, despite a lack of evidence; to my knowledge, the observability of “interference with chemotherapy by coffee” has never been subjected to a disciplined inquiry. And in fact, early biological evidence suggests the opposite is probably true. Woo and colleagues¹⁴ have demonstrated that addition of cafestol overcomes ABT-737 resistance in both human glioma cells and human breast carcinoma cells. Lima et al¹⁵ showed that addition of cafestol to Ara-C inhibited human leukemia cells more than either agent alone. Further, Min¹⁶ et al more effectively induced apoptosis in renal cell carcinoma Caki cells with the addition of kahweol to sorafenib. These results suggest profound opportunities for research.

How Much Cafestol and Kahweol Are Required for Anticancer Effects?

Atsushi Mizokami, Hiroaki Iwamoto, et al, of Kanazawa University enthusiastically reported results of a prostate cancer xenograft study of SCID mice, observing that “oral administration of kahweol acetate and cafestol significantly inhibited tumor growth.” They further suggested that cancer patients taking 3-4 cups of boiled, unfiltered coffee (French, Turkish) by mouth could achieve concentrations of 30 μM for each of the diterpenes, “at which both exerted anti-cancer effects” (in RCC in vitro).¹⁷

Iwamoto’s math is straightforward. Given the average adult blood volume of 5 liters and a putative absorption efficiency of 70% across the gut wall, the amounts of cafestol (78.8 mg)  and kahweol (68.8 mg) present in four 150-ml cups of French-pressed unfiltered coffee are sufficient to reach serum concentrations high enough (30 μM) to provoke the anticancer effects previously demonstrated in RCC, and presumably in others, as shown in vitro (mesothelioma, pulmonary adenocarcinoma, NSCLC, oral SCC, prostate, breast, colorectal, RCC, HCC, leukemia, fibrosarcoma, and head and neck SCC). Only RCC and prostate cancer have been studied in vivo so far, in animal models.

How Much Cafestol and Kahweol Are in Gerson’s Coffee Enemas?

By comparison, Gerson-style continuous application of coffee enemas every 4-6 hours around the clock must have far greater effects on serum levels. Most patients receive five coffee enemas per day for a probable bioavailability of the daily total of 3.5 grams each of both cafestol and kahweol (that’s 7 grams total of these nearly identical diterpenes).

The amounts of cafestol (~1 g) and kahweol (~1 g) present in a single coffee enema prepared per Max Gerson’s written instructions — 3 heaping Tbsp (~35 grams) coffee, boiled 10 minutes in 1 liter water, strained but unfiltered — are nearly 13 times the anticancer amount identified by Iwamoto. In contrast to the 30 μM levels of the Kanazawa University researchers, a single coffee enema probably achieves a level in the neighborhood of  >400 μM for each diterpene.

Of interest is an unpublished archival transcript of a 1950s interview with Dr Maurice Kowan in which Gerson described a strong coffee enema prepared by boiling 5-6 Tbsp (~70 grams) coffee in only 1 pint of water.¹⁸ A single strong enema could conceivably deliver 1.4 grams each of cafestol and kahweol. The serum levels of cafestol and kahweol resulting from this enema could be as high as ~890 μM, which would be nearly thirtyfold the putative anticancer level published by Mizokami and Iwamoto.

But There Is More to Coffee Than Cafestol and Kahweol

Much of this paper has dealt with kahweol and cafestol, because they are far better studied than raw coffee beans. However, it is well worth noting that Edward Miller¹⁹ demonstrated enormous inhibition of DMBA-induced tumors in the buccal pouches of hamsters by feeding them chow that was blended 20% with powdered green coffee beans. Incidence was reduced by 70% and the number of tumors was reduced by 90% by green coffee beans. In later experiments,²⁰ Miller showed that purified kahweol and cafestol together inhibited tumor development by only 35%. It is obvious that components of coffee beyond kahweol and cafestol contribute to its anticancer effects. As Miller wrote, “green coffee beans may contain other cancer chemopreventive agents”

In addition to cafestol and kahweol, other anticancer components of coffee include caffeine, caffeic acid, chlorogenic acid, p-coumaric acid, ferulic acid, hydroxyhydroquinone, 5hydroxymethylfurfural, melanoidins, N-methylpyridinium, phenolic compounds and polysaccharides. A capable review of these agents was produced by Diederich and colleagues.²¹

Coffee as a whole substance minimally processed should remain in the foreground of research. By way of analogy, let me offer this gem from Sir Frederick Gowland Hopkins: “We thought we were feeding our animals proteins, fats and carbohydrates, but what we were really giving them was carrots and oats.”²²

Recap

To briefly recap, this paper is about coffee enemas. It is not a call for more research into the anticancer components of coffee, rather a suggestion for rethinking coffee enemas themselves. Disciplined inquiries should regard the coffee enema as a potential anticancer measure, and efforts should be made to monitor this variable in association with other key variables such as chemotherapy, radiation, surgery, tumor responses, and overall survival.

References

1. Hildenbrand GL, Hildenbrand LC, Bradford K, Cavin SW. Five-year survival rates of melanoma patients treated by diet therapy after the manner of Gerson: a retrospective review. Altern Ther Health Med. 1995 Sep;1(4):29-37.
2. Lam LK, Sparnins VL, Wattenberg LW. Isolation and identification of kahweol palmitate and cafestol palmitate as active constituents of green coffee beans that enhance glutathione S-transferase activity in the mouse. Cancer Res. 1982 Apr;  42(4):1193-8.
3. Rowe JD, Nieves E, Listowsky I. Subunit diversity and tissue distribution of human glutathione S-transferases: interpretations based on electrospray ionization-MS and peptide sequence-specific antisera. Biochem J. 1977; 325:481-486.
4. Singh RR, Reindl KM. Glutathione S-Transferases in Cancer. Antioxidants. 2021;10:701-725.
5. Matzinger, P. Tolerance, Danger, and the Extended Family. Annu Rev Immunol. 1994; 12(1), 991–1045.
6. Fuchs EJ, Matzinger P. Is cancer dangerous to the immune system? Semin Immunol. 1996 Oct; 8(5):271-80.
7. Coley WB. The Treatment of Malignant Disease by the Injection of Toxins of Erysipelas. Br Med J. 1897 Mar 6; 1(1888):625.
8. Cope FW. A medical application of the Ling association-induction hypothesis: the high potassium, low sodium diet of the Gerson cancer therapy. Physiol Chem Phys. 1978 Jan 1; 10(5):465-468.
9. Lechner P, Kronberger Jung I. Erfahrungen mit dem einsatz der Diät-therapie in der chirurgischen Onkologie. Aktuelle Ehnährungsmedizin. 1990; 15:72-78. “Table 5 summarizes briefly the disease process of a now 77-year-old woman … in which we were able to observe a complete remission without conventional therapy.” The patient had complete remission of numerous bilateral hepatic metastases (largest 7cm) from a primary carcinoma of the sigmoid (pT3N1M0G3).
10. Kim JY, Jung KS, Jeong HG. Suppressive effects of kahweol and cafestol on cyclooxygenase-2 expression in macrophages. FEBS Lett. 2004 Jul 2; 569(1-3):321-6.
11. Gerson M, (Hildenbrand GLG editor). A Cancer Therapy: Results of Fifty Cases. 4th ed, San Diego, CA; Gerson Institute; 1986:125.
12. Eldesouki S, El-Huneidi W, et al. Recent Updates on the Functional Impact of Kahweol and Cafestol on Cancer. Molecules. 2022; 27:7332-7347.
13. Kotowski U, Thurnher D, et al. Effect of the coffee ingredient cafestol on head and neck squamous cell carcinoma cell lines. Strahlenther Onkol. 2015; 191:511-517. Kotowski also demonstrated a protective effect of cafestol against cisplatin; however, the plasma half-life of cisplatin is only 30 minutes, and coffee is unlikely to be administered during the chemo IV.
14. Woo SM, Min KJ, et al. Cafestol overcomes ABT-737 resistance in Mcl-1-overexpressed renal carcinoma Caki cells through downregulation of Mcl-1 expression and upregulation of Bim expression. Cell Death Dis. 2014;5:e1514.
15. Lima CS, Spindola DG, et al. Cafestol, a diterpene molecule found in coffee, induces leukemia cell death. Biomed Pharmacother. 2017; 92:1045-1054.
16. Min KJ, Um HJ, Kwon TK. The coffee diterpene kahweol enhances sensitivity to sorafenib in human renal carcinoma Kaki cells through downregulation of Mcl-1 and c-FLIP expression. Oncotarget 2017; 8:83195-83206.
17. Iwamoto H, Mizokami A, et al. Coffee diterpenes kahweol acetate and cafestol synergistically inhibit the proliferation and migration of prostate cancer cells. The Prostate. 2019; 79:468-479.
18. Gerson M. Unpublished transcript of an interview with Dr Maurice Kowan, undated (probably early 1950s). Archives of the Gerson Research Organization and the Gerson Institute: “If (the caffeine) enema is not sufficient and the patient has very bad pain, he has very bad swellings, edema — and all these concern tuberculosis patients — it is advisable to give a stronger acting enema. For this purpose, I found we can give these patients half a quart, a pint, of black strong coffee. The word ‘strong’ coffee is a little bit lax. Now to make it a little more precise, I would like to tell you to use a pint of water, 5-6 heaping tablespoons of ground coffee. Let it boil about 10 to 15 minutes and then you let it flow in slowly about 10 to 15 minutes, after that you wait and then you have a much stronger elimination.”
19. Miller EG, et al. Inhibition of hamster buccal pouch carcinogenesis by green coffee beans. Oral Surgery. June 1988; 65(6):745-749.
20. Miller EG, et al. Kahweol and Cafestol: Inhibitors of Hamster Buccal Pouch Carcinogenesis. Nutr. Cancer. 1991; 15(1):41-46.
21. Gaascht F, Dicato M, Diederich M. Coffee provides a natural multitarget pharmacopeia against the hallmarks of cancer. Genes Nutr. 2015; 10:51-67.
22. Hopkins FG in Shohl AT. Mineral Metabolism. Issue 82 of Monograph Series, American Chemical Society; Reinhold, 1939.

Published July 15, 2023

About the Author

Gar Hildenbrand is an epidemiologist, federal policy expert, and long-time political activist for reform of the cancer industry. As a whistle-blowing advisor to the US Office of Technology Assessment (OTA), he exposed covert quackbusters on the OTA staff and helped save the study Unconventional Cancer Treatments. US Senator Tom Harkin (Iowa)  then tapped Gar to aid the formation of a new coordinating office in the Office of the Director of the National Institutes of Health (Office of Alternative Medicine) and was promptly labeled a “Harkinite” in the pages of Science magazine.

Gar’s methodology was recognized when he was asked to give a keynote speech, following Ernst Wynder, at the NIH Practice-Based Outcomes Monitoring and Evaluation System (POMES) Methodology Conference. The subject was the collection and assessment of outcomes of a 20-year consecutive series of melanoma patients treated in four licensed medical facilities with the Gerson cancer therapy.

The striking survival advantage of Gerson-treated melanoma patients spurred Gar to ask how that happened. How could Gerson’s dietotherapy alter the course of cancer? His inquiry continues with the current publication. According to Gar, “The science is so cool, its like playing in a sandbox; I will die a very old child.”