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Broccoli and COPD: The Doctrine of Signatures revisited

Jacob Schor ND, FABNO

May 1, 2011



A recent study from the research labs of Johns Hopkins University brings to mind the earlier days of medicine, a time in which there existed a serious premise called the Doctrine of Signatures.  It was believed that those plant materials that in some manner resembled parts of the body would be useful in treating those same organs.  Paracelsus is often given credit for originating this concept.  Andrew White in his 1896 treatise on the ‘warfare of science with theology’ summed it up like this:



"It was reasoned that the Almighty must have set his sign upon the various means of curing disease which he provided; hence it was held that bloodroot, on account of its red juice, is good for the blood; liverwort, having a leaf like the liver, cures diseases of the liver; eyebright, being marked with a spot like an eye, …. "



Today this doctrine is considered ‘magical thinking’ and few in the scientific world pay heed to it.  Yet imagine a broccoli floret bisected lengthwise and held upside down.  Could these branching stems not resemble the branching bronchi and bronchioles of the lungs?


Broccoli contains a chemical called sulforaphane that both protects against cancer and may also kill cancer cells.  It now appears that this same chemical may aid the immune system in clearing infectious material out of the lungs.  This idea comes from the laboratory of Shyam Biswal at Johns Hopkins University, which has recently produced several fascinating papers on the possibility of sulforaphane playing a role in treating chronic obstructive pulmonary disease (COPD).


COPD is one of the most common lung diseases. It makes it difficult to breathe. There are two types of COPD, either chronic bronchitis, defined by a long-term cough with mucus or emphysema, defined by the gradual destruction of the lungs over time


Most people with COPD have a combination of both conditions; Chronic cough and lung destruction.  The leading cause of COPD is smoking. 


COPD affects 24 million Americans and is now the third leading cause of death in the United States.   Bacterial and viral respiratory infections worsen the condition and cause permanent declines in lung function. Currently none of the available treatments for COPD actually address the underlying problems in the lungs, all they do is treat symptoms.  Thus the data coming from Biswal’s lab at Johns Hopkins is quite significant: it speaks to actually intervening in the disease process.


There are specialized macrophages, white blood cells, in the lungs that remove debris and bacteria from the lungs before they cause infection. In smokers who develop COPD this macrophage cleanup crew isn’t doing its job well and their slacking off on their jobs leads to frequent and long lasting infection. 


Biswal et al back in 2008 figured this out and wrote a plausible proposal that broccoli might be protective. It all has to do with a chemical pathway in the lungs called NRF2 that is involved an activating lung macrophages and that is inactivated by cigarette smokw.


One of our readers recently wrote asking that I not use abbreviations without first defining them. NRF2 is short for ‘nuclear factor erythroid 2 related factor 2.’  There is an obvious reason why the term is usually abbreviated.  NRF2 is a basic “cap and collar” leucine zipper transcription factor that regulates a cell’s response to environmental stress.  NRF2 activates the expression of genes that code for antioxidants and detoxification enzymes.  If NRF2 doesn’t work, then cells can’t make antioxidants or protect themselves from toxins.


NRF2 is inactivated by cigarette smoke and this causes a chain reaction where the damage caused by smoke is amplified.  Biswal’s lab reported in 2004 that mice without a functional NRF2 gene became very sensitive to cigarette smoke; exposure rapidly led to emphysema. NRF2 response has also been shown to be important in controlling reaction to acute lung injury and allergic asthma.    Thus NRF2 is important not just in COPD but also in the other major lung illnesses.


The more advanced a patient’s COPD is, the faster the NRF2 is broken down in their body and the less able they are to protect themselves against the disease.


These same researchers have also found that sulphoraphane, a plant chemical made by broccoli, cauliflower and other cruciferous vegetables can restore the NRF2 pathway.


This brings us to the current study published in April 2011 in the journal Science Translational Medicine by Biswal’s lab.  They isolated macrophages from the lungs of 43 people with COPD.  These macrophages, because their NRF2 levels were low, did little to prevent bacterial infections.  The researchers then exposed the macrophages to two strains of bacteria Haemophilus influenza, and Pseudomonas aeruginosa, both of which commonly cause lung infection in patients with COPD. Treating the defective macrophages with sulforaphane restored the NRF2 pathway and the ability of macrophages to engulf and destroy these bacteria. The researchers after demonstrating this effect then set up an experiment with mice.  


They exposed mice to cigarette  smoke for either one week or for six months. Both groups of mice ended up with increased bacterial colonization in the lungs, just like what happens in COPD. Treating the mice with sulphoraphane, sped up bacterial clearance and protected the mice from lung infection. 


These are important results.  The researchers have already begun a clinical trial in humans to see if sulforaphane provides the same kind of benefit predicted by these earlier studies.  It will be three years though until we see their results.


This could turn out to be huge. 


It should be noted that although broccoli and the other cruciferous vegetables provide sulforaphane, it is still in an inactive form.  It needs to be activated by an enzyme called myrosinase that is found in the raw vegetables.   Myrosinase is released from vacuoles in the cells as they are crushed say in the process of chewing.  Myrosinase is destroyed by high temperature so well cooked vegetables, even if they contain plenty of sulforaphane, will not be activated.  Adding even a small serving of raw cruciferous vegetables, which still contain myrosinase, to a meal of cooked cruciferous vegetables is enough to activate much or all of the sulforaphane. This is of particular interest as there are an increasing number of brands of ‘broccoli powder sold as nutritional supplements that may yield only meager increases in blood sulforaphane levels.   Adding small amounts of broccoli sprout powder at the same time these products are taken may significantly increase the sulforaphane levels in the blood. Certainly it now makes good sense to eat a small serving of raw broccoli along with any cooked broccoli. 



Past Newsletters on similar topics: 


Raw broccoli doubles survival in bladder cancer

July 1, 2010

Li Tang's recent paper tells us that eating raw broccoli once a month may cut the risk of dying from bladder cancer by more than half.


Broccoli Sprout Update[this is old, pre-2004]







White, Andrew Dickson, A history of the warfare of science with theology in Christendom. Appleton and company, New York 1896

Full text: http://ia600302.us.archive.org/33/items/cu31924022599330/cu31924022599330.pdf


Barnes PJ. Defective antioxidant gene regulation in COPD: a case for broccoli. Am J Respir Crit Care Med. 2008 Sep 15;178(6):552-4.


Free Article: http://ajrccm.atsjournals.org/cgi/reprint/178/6/552


Rangasamy T, Cho CY, Thimmulappa RK, Zhen L, Srisuma SS, Kensler TW, Yamamoto M, Petrache I, Tuder RM, Biswal S. Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. J Clin Invest. 2004 Nov;114(9):1248-59.


Free PMC Article:



Thimmulappa RK, Lee H, Rangasamy T, Reddy SP, Yamamoto M, Kensler TW, Biswal S. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J Clin Invest. 2006 Apr;116(4):984-95.


Full Text Free: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421348/pdf/JCI0625790.pdf


Williams MA, Rangasamy T, Bauer SM, Killedar S, Karp M, Kensler TW, Yamamoto M, Breysse P, Biswal S, Georas SN. Disruption of the transcription factor Nrf2 promotes pro-oxidative dendritic cells that stimulate Th2-like immunoresponsiveness upon activation by ambient particulate matter. J Immunol. 2008 Oct 1;181(7):4545-59.

Full text Free: http://www.jimmunol.org/content/181/7/4545.full.pdf+html


Malhotra D, Thimmulappa R, Vij N, Navas-Acien A, Sussan T, Merali S, Zhang L, Kelsen SG, Myers A, Wise R, Tuder R, Biswal S. Heightened endoplasmic reticulum stress in the lungs of patients with chronic obstructive pulmonary disease: the role of Nrf2-regulated proteasomal activity. Am J Respir Crit Care Med. 2009 Dec 15;180(12):1196-207.

Free PMC Article



Harvey CJ, Thimmulappa RK, Sethi S, Kong X, Yarmus L, Brown RH, Feller-Kopman D, Wise R, Biswal S. Targeting Nrf2 Signaling Improves Bacterial Clearance by Alveolar Macrophages in Patients with COPD and in a Mouse Model. Sci Transl Med. 2011 Apr 13;3(78):78ra32.


Cramer JM, Jeffery EH. Sulforaphane absorption and excretion following ingestion of a semi-purified broccoli powder rich in glucoraphanin and broccoli sprouts in healthy men. Nutr Cancer. 2011;63(2):196-201.