Durk Pearson & Sandy Shaw’s®
Life Extension NewsTM
Volume 15 No. 1 • January-February 2012


There is no Constitutional Basis Under the Commerce Clause for the Federal Government to Force You to Buy Broccoli* (or Obamacare*), But We Do Recommend Eating Broccoli and/or Other Cruciferous Vegetables. Here’s Why.

New research continues to be published on the beneficial health effects of cruciferous vegetables (the Brassicaceae family which includes broccoli, cabbage, brussels sprouts, cauliflower, and mustard). Much of this new work concerns a link between normal intestinal immune function and the aryl hydrocarbon receptor (AhR), for which the cruciferous vegetables contain moledules that are ligands (activating the receptor).1–3

One paper1 reports that intraepithelial lymphocytes (IELs) from intestine and skin promote epithelial repair following injury, as well as limiting epithelial cell invasion by the hordes of indigenous bacteria that reside in the gut.1 In answer to the question of what normal physiological signals activate the AhRs, researchers found that certain tryptophan derivatives found in plants (such as indole-3-carbinol, as is found in cruciferous vegetables) are converted into high-affinity AhR ligands as a result of encountering the acidic environment of the stomach.1 The commentary article2 on the paper by Li et al1 proposes that the link between diet, AhRs, and intestinal immunity “suggest a mechanistic basis for the epidemiological link [between diets low in fruits and vegetables and inflammatory bowel disease] and offer the prospect of using AhR ligands as ‘nutraceuticals’ to boost intestinal immunity.”

In the paper by Li et al,1 the authors note that “[a]s a consequence of low AhR activity [in intestinal epithelial cells], the intestine is in a heightened state of immune activation, dominated by a type 1 [proinflammatory] response and more susceptible to immunopathology.” In one experiment performed by the authors and reported in Li et al,1 the researchers induced colitis in mice using dextran sodium sulfate (DSS). In control mice, DSS treatment resulted in rapid weight loss but full recovery following withdrawal of DSS after 6 days. However in mice lacking AhR, DSS caused accelerated weight loss, extreme shortening of the colon, and severe hemorrhaging, with 11 of the 16 AhR-deficient mice losing over 20% of body weight. But the AhR-deficient mice fed the purified diet supplemented with indole-3-carbinol showed only mild signs of colitis, reduced weight loss and reduced shortening of the colon with rapid recovery after withdrawal from DSS.

In the paper by Kiss et al,4 the researchers sum up the paper’s research: “Our results establish a molecular link between nutrients [AhR ligands] and the formation of immune system components [intestinal lymphoid follicles] required to maintain intestinal homeostasis and resistance to infections.” The researchers note that, interestingly, “the diverse glucosinolates play an important role in plant resistance to mildew fungi and insect herbivores, suggesting an evolutionarily conserved role in immune defense pathways.” This helps explain why the cruciferous vegetables go to the trouble of making these molecules in the first place.

Even the New England Journal of Medicine5 has reported on the two new studies (Li et al1 and Kiss et al4) linking AhR ligands from cruciferous vegetables and intestinal immunity. In its commentary, the New England Journal of Medicine author notes that the two studies suggest that AhR ligands may not only help prevent diseases such as inflammatory bowel disease (IBD) but may be effective treatments for IBD, metabolic syndrome, and other diseases. Moreover, the author says, “[b]eneficial effects of AhR ligands are known to be associated with an increase in levels of interleukin-22, a cytokine that supports intestinal integrity, and the production of mucus and defensins (a class of anti-microbial peptides).”

How to Eat Cruciferous Vegetables for Greatest Benefit

As reported in a recent paper,6 cruciferous vegetables contain “high levels of glucosinolates, a class of phytochemicals not found in any other vegetable.” In order to get the healthful metabolites (isothiocyanates, ITCs) that include sulforaphane and indole-3-carbinol requires the activity of an enzyme, myrosinase, found in the cruciferous vegetables themselves and also in gut microbial flora. “A small number of studies in animals and humans have found that inactivation of myrosinase decreases the availability of ITCs.” As this paper6 also reports, the glucosinolate precursors to sulforaphane are highest (measured as concentration per plant weight) in the seeds followed by the sprouts. The authors compared the urinary isothiocyanate metabolites in healthy subjects who ate either broccoli sprouts or a broccoli supplement (no myrosinase) containing equivalent amounts of glucosinolate. They found significantly lower amounts of ITC metabolites excreted in the urine of those consuming the supplement as compared to the sprouts, which they attribute to the lack of myrosinase in the supplement.

Plasma measurements of sulforaphane were made in people who had consumed broccoli soup (100 g. florets microwaved for 90 seconds); levels reached 2-3uM which the authors report is almost entirely excreted in the urine within 24 hours.7 Thus, the authors of this paper7 assumed “that higher SFN [sulforaphane] plasma levels may be reached by consuming broccoli sprouts, which contains 100 times higher levels of glucoraphanin or by the intake of synthetic glucoraphanin or purified SFN.”

In another study reported in the Oct 2011 Food Technology (shamefully, no reference was provided, other than that the work was done by researchers at the University of Illinois, Urbana), pairing fresh broccoli with certain spicy foods which contain myrosinase (mustard, horseradish, and wasabi) provide the maximum health benefits of the broccoli by ensuring that sulforaphane is formed and absorbed in the upper digestive tract.

Sulforaphane in the Treatment of Pancreatic Cancer

Incidentally, the broccoli isothiocyanate sulforaphane “was recently identified as being capable of eliminating highly therapy-resistant pancreatic carcinoma (PC) cells without inducing toxic side effects.”7 As the authors7 explain, “[h]igh levels of glucoraphanin, the glucosinolate precursor of SFN, are present in broccoli and cauliflower.” “SFN has attracted much attention since the discovery of its anti-tumor effects in PC [pancreatic carcinoma] and several other tumor cell lines.” Three references are cited in Ref. 7 as documentation for the anti-tumor effects of SFN in pancreatic cancer. As pancreatic cancer is highly deadly (with a mean 5-year survival rate of less than 1%), we hope there is significant followup on the potential use of SFN in its treatment (one of Sandy’s aunts died of the disease, so she is personally interested in its treatment in case there is a genetic relation to risk). However, as sulforaphane is a natural compound, it cannot be patented; hence, it is unlikely to be of interest to pharmaceutical companies except as a lead to the development of synthetic analogs.


*See our take on some recent legal arguments on whether the federales have the Constitutional authority to force you to buy broccoli (as an analogy to the Obamacare mandate that forces you to buy government health “insurance”) in the June-July 2011 issue of Durk Pearson & Sandy Shaw’s® Life Extension Newsletter.™


References

  1. Li et al. Exogenous stimuli maintain intraepithelial lymphocytes via aryl hydrocarbon receptor activation. Cell 147:629-40 (2011).
  2. Hooper. You AhR what you eat: linking diet and immunity. Cell 147:489-91 (2011).
  3. Bjeldanes et al. Aromatic hydrocarbon responsiveness- receptor agonists generated from indole-3-carbinol in vitro and in vivo: comparisons with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Proc Natl Acad Sci USA 88:9543-7 (1991)
  4. Kiss et al. Natural aryl hydrocarbon receptor ligands control organogenesis of intestinal lymphoid follicles. Science 334:1561-5 (2011).
  5. Tilg. Diet and intestinal immunity. N Engl J Med 366(2):181-3 (2012).
  6. Clarke et al. Comparison of isothiocyanate metabolite levels and histone deacetylase activity in human subjects consuming broccoli sprouts or broccoli supplements. J Agric Food Chem 59:10955-63 (2011).
  7. Naumann et al. Autophagy and cell death signaling following dietary sulforaphane act independently of each other and require oxidative stress in pancreatic cancer. Int J Oncol 39:101-9 (2011).

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