Science & Evidence

For decades, critics dismissed the Hoxsey formula as worthless quackery. Yet modern scientific research has revealed that many of its ingredients contain compounds with genuine anticancer properties. The tragedy is not that Hoxsey's herbs were ineffective, but that organized medicine refused to test them properly—leaving a question that remains unanswered to this day.

The Central Paradox

Eight of nine Hoxsey tonic herbs have demonstrated antitumor activity in scientific studies. Individual ingredients have progressed to human clinical trials. Yet the complete Hoxsey formula—the actual treatment given to tens of thousands of patients—has never been tested in a clinical trial. Not because it failed testing, but because the medical establishment refused to test it.

The USDA Assessment

In 1988, Dr. James A. Duke—Chief of the USDA's Plant Taxonomy Laboratory and one of the world's foremost authorities on medicinal plants—published a detailed analysis of the Hoxsey herbs in HerbalGram. His findings systematically contradicted decades of dismissal:

Duke's Key Findings

  1. All Hoxsey herbs have Native American traditions of cancer usage, some extending back 3,000+ years
  2. Several contained compounds of interest to the National Cancer Institute
  3. Eight of nine herbs demonstrated antitumor activity in animal models
  4. Five herbs showed significant antioxidant effects
  5. All nine herbs exhibited antimicrobial activity
  6. Only one (poke root) was identified as potentially toxic

Duke's overall assessment: The Hoxsey formula demonstrated "very significant chemical and biological anticancer activity."

The OTA Report (1990)

The most thorough government review of Hoxsey therapy came from the U.S. Office of Technology Assessment. Commissioned by Congress and titled Unconventional Cancer Treatments, the report's analysis by medical historian Patricia Spain Ward reached a remarkable conclusion:

"Orthodox scientific research has identified antitumor activity of one sort or another in all but three of Hoxsey's plants."

"More recent literature leaves no doubt that Hoxsey's formula...does indeed contain many plant substances of marked therapeutic activity."

— Patricia Spain Ward, PhD, University of Illinois at Chicago

The report acknowledged Hoxsey as "one of the longest-lived unconventional therapies of the 20th century" and noted it retained "great popular appeal despite unrelenting opposition." The critical caveat: while individual components showed promise, the complete formula remained untested because no institution had been willing to conduct the necessary trials.


Individual Herb Research

Modern research has validated the anticancer potential of several Hoxsey ingredients. Here are the most significant findings:

Berberine (from Barberry): The Strongest Evidence

Berberine, the active compound in barberry root, has become one of the most studied natural compounds for cancer prevention. The evidence includes the largest randomized controlled trial ever conducted on a Hoxsey ingredient.

CBAR Study: Colorectal Adenoma Prevention

NCT02226185 | Published in The Lancet Gastroenterology & Hepatology

Study Design

  • 1,108 participants across 7 hospitals in China
  • Randomized, double-blind, placebo-controlled
  • 0.3g berberine twice daily vs. placebo

Primary Results

  • Adenoma recurrence: 36% vs. 47% (RR 0.77, p=0.001)
  • Advanced adenomas: 3% vs. 6%
  • Number needed to treat: 9

Six-Year Follow-Up (2024)

  • 781 patients followed long-term
  • Adenoma recurrence: 34.7% vs. 52.1%
  • Benefits persisted years after treatment ended

Researchers concluded berberine "might be a crucial secondary chemopreventive agent for colorectal adenoma."

PubMed: 40795846 →

Arctigenin (from Burdock Root): Phase I Clinical Trial

Arctigenin, a lignan from burdock root, has shown remarkable potency in laboratory studies and has been tested in human cancer patients.

GBS-01 Phase I Trial

National Cancer Center Hospital East, Japan | Cancer Science (2016)

Laboratory Findings

  • IC50 vs. HepG2 liver cancer: 4.74 nM
  • IC50 vs. Hep3B liver cancer: 59.27 nM
  • Exceptionally potent compared to many drugs

Clinical Trial Results

  • 15 patients with gemcitabine-refractory pancreatic cancer
  • Doses: 3g to 12g orally
  • Results: 1 partial response, 4 stable disease
  • No dose-limiting toxicities
  • Median overall survival: 5.7 months
PubMed: 27685612 →

Red Clover Isoflavones

Mechanisms of Action

  • Genistein and daidzein induce apoptosis (programmed cell death) in colon cancer cells
  • Upregulates caspase-8 expression, a key enzyme in apoptosis
  • Inhibits PI3K activity, disrupting cancer cell survival signaling
  • Arrests cell cycle at G1 or G2/M phases, preventing cancer cell division
  • Binding to actin restricts cancer cell migration and metastasis

Important note: Red clover acts as an estrogen agonist and may stimulate ER-positive breast cancer cells. Memorial Sloan Kettering advises breast cancer patients to avoid it.

Licorice Root Compounds

Glycyrrhizin Research

  • Root contains 3-13% glycyrrhizin by weight
  • Active metabolite: 18-beta-glycyrrhetinic acid (GA)
  • Inhibits NF-kappaB, protein kinase C, and Ras pathways
  • Induces apoptosis via MAPK/STAT3/NF-kappaB signaling
  • CDK4-Cyclin D1 downregulation causes G0/G1 cell cycle arrest
  • Increases CD8+ T cell infiltration into tumors

Over 400 cytotoxic derivatives have been prepared from licorice compounds, with 128 derivatives showing IC50 values below 30 microM against cancer cell lines.


Evidence Summary Table

Ingredient In Vitro Animal Human Trials Evidence Level
Berberine (Barberry) Strong Yes RCT (1,108 patients) Moderate-High
Arctigenin (Burdock) Strong Yes Phase I Low-Moderate
Licorice (Glycyrrhizin) Strong Yes Phase II (combination) Low-Moderate
Red Clover Strong Yes Limited Low
Bloodroot Moderate Limited None Very Low
Prickly Ash Moderate Limited None Very Low
Stillingia Limited None None Very Low
Poke Root Limited Limited None Very Low

The Hoxsey Paste and Mohs Surgery

Perhaps the most striking validation of Hoxsey's work came not from clinical trials but from the operating room. The external paste Hoxsey used for skin cancers—zinc chloride, bloodroot, and antimony trisulfide—was nearly identical to the formula Dr. Frederic Mohs used to develop Mohs micrographic surgery in 1933.

What Mohs Proved

  • The zinc chloride paste could fix cancerous tissue for microscopic examination
  • When combined with staged excision and microscopy, cure rates exceeded 99%
  • Mohs surgery became the gold standard for certain skin cancers

The Critical Difference

  • Mohs used microscopic verification to ensure complete removal
  • Hoxsey used the paste alone without microscopic confirmation
  • Mohs later criticized using escharotics alone as unreliable

During his 1948 deposition in the libel case, Morris Fishbein was forced to admit under oath that Hoxsey's paste did work for external cancers. This admission—extracted from the AMA's most vocal critic of Hoxsey—stands as sworn testimony that at least part of the Hoxsey treatment had genuine efficacy.


The Medical Establishment Response

Despite the evidence reviewed above, major medical organizations have maintained their opposition to Hoxsey therapy:

Organization Position Note
U.S. Food and Drug Administration Banned (1960) Called it "worthless and discredited"
National Cancer Institute Insufficient evidence Never conducted clinical trials
American Cancer Society No evidence of effectiveness Never conducted clinical trials
Memorial Sloan Kettering Not recommended Acknowledges individual herb activity

The pattern is consistent: these organizations state there is no evidence of effectiveness, yet none of them has conducted or funded the clinical trials that would generate such evidence. The 1953 Fitzgerald Report to Congress directly addressed this:

"Public and private funds have been thrown around...to close up and destroy clinics, hospitals, and scientific research laboratories which do not conform to the viewpoint of medical associations."

— Benedict F. Fitzgerald Jr., Special Counsel to the U.S. Senate

Why the Formula Was Never Tested

The question of why a formula used by tens of thousands of patients was never subjected to proper clinical trials has multiple answers:

Institutional Opposition

From its earliest days, the AMA targeted Hoxsey for destruction. Morris Fishbein's "Bureau of Investigation" labeled the treatment a fraud without testing it, and the organization spent decades lobbying for its prohibition.

Regulatory Barriers

After the FDA ban in 1960, conducting clinical trials in the United States became legally impossible. The Bio-Medical Center in Mexico operates outside the FDA's jurisdiction but lacks the resources for large-scale clinical research.

Economic Factors

The herbs in the Hoxsey formula cannot be patented. Pharmaceutical companies have no incentive to fund expensive trials for treatments they cannot own. Only non-profit or government funding could support such research.

Methodological Challenges

Hoxsey therapy includes not just the herbal tonic but dietary changes and other components. Designing a controlled study for a multi-component treatment presents genuine scientific challenges.


The Bottom Line

The scientific evidence tells a more nuanced story than either Hoxsey's fiercest advocates or harshest critics have acknowledged. The herbs in his formula contain compounds with genuine anticancer properties—properties now confirmed by modern research, including randomized controlled trials.

Yet the complete Hoxsey formula has never been tested. This is not because it failed testing, but because the institutional will to test it never existed. The question Patricia Spain Ward raised in 1990 remains unanswered: Does the specific combination of herbs in the Hoxsey formula have therapeutic value beyond its individual components?

Until that trial is conducted, we are left with a paradox: a treatment dismissed as worthless, yet containing ingredients that modern science has validated as genuinely active against cancer.


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