Problematic rodent sulforaphane studies

I was asked to give an example of Human relevance of rodent sulforaphane studies. I’ll use the 2020 Sulforaphane Diminishes the Formation of Mammary Tumors in Rats Exposed to 17β-Estradiol.

1. This study’s sulforaphane dose was “100 μmol/kg SFN..gavage regimen on Monday, Wednesday and Friday for 56 weeks.” From the October 2019 Broccoli or Sulforaphane: Is It the Source or Dose That Matters? “Allometric scaling uses the correction factor for rat doses 0.162” and this graphic:

Interpreting the human-relevant range:

Interpreting that 8% of the rodent studies were clinically relevant to human sulforaphane doses as a lower boundary (1.43 µmol / kg) and tolerable to humans as an upper boundary (4 µmol / kg):

A human equivalent of this study’s dose is (100 μmol/kg x .162) = 16.2 µmol / kg. See the original blog post for a study showing that a majority of both treatment and control group subjects will refuse and stop with sulforaphane doses less than half of this study’s human equivalent.

2. From Week 28, “The maximum lifespan for rats and humans were set to 3.8 years and 122.5 years, respectively.” A human-equivalent multiplication factor that can be applied to a rat post-development time period is 122.5 / 3.8 = 32.2.

Assuming this study’s subjects could achieve maximum lifespan, a human equivalent of 56 weeks is (56 x 32.2) ≈ 1,803 weeks, or ≈ 34.7 years.

3. Let’s assert that the main purpose of animal studies is to help humans.

Was it possible for this study to achieve this goal when it used intolerable human-equivalent sulforaphane doses for a period equivalent to over three decades of our lives?

Yet its Discussion section proposed that it’s useful for human guidance on:

  • Obesity;
  • Breast cancer in premenopausal and postmenopausal women;
  • Hormone status;
  • Phospholipids for cellular health and homeostasis;
  • Serum free fatty acids and triglycerides; and
  • Lipid metabolism and DNA damage.

4. These researchers definitely knew what this study was going to do. A coauthor of the above referenced 2019 paper was also a coauthor of this study, who “conceived the original study design and supervised the project.”

Why did they do it? The coauthor’s shared apology – published in the October 2019 paper – for these types of studies was:

“Animal studies have not delivered all that might be expected of them. Pre-clinical experimentalists have not thought carefully about the selection of dose (or route) and its relevance to clinical utility.

Authors of this review have contributed to this dose skewing.”

This study was published in July 2020.

It wasn’t just a waste of resources. It detracted from science because people won’t recognize that its findings are inapplicable to humans.

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