Walking in the woods, graffiti, cancer, obesity, and other related subjects
August 30, 2005
Subject: Graffiti is bad for your health. Walking in the woods is good for you.
According to a recent study, “People living in concrete jungles surrounded by graffiti are more likely to be obese than those on the edge of green open spaces ….” 
The study was published in the British Medical Journal last week: More than 50% of the Welsh adult population are now classed as overweight or obese, compared to the UK average of 16%.
Researchers from the Medical Research Council in Wales set out to discover whether living in less-pleasant areas was linked to higher levels of obesity. They tested the theory that living in pleasant areas with lots of green spaces and less rubbish encourages people to exercise more. The researchers assessed the local environment in the cities studied, taking into account factors such as graffiti, litter and dog mess as well as levels of vegetation and greenery visible in the area.
They found that people living in greener areas were three times more likely to be physically active than those living in less green places. Their likelihood of being overweight or obese was about 40% less.
But in contrast, those people living in areas with high amounts of litter and graffiti and less greenery were 50% less likely to be physically active. Their likelihood of being overweight or obese was also 50% higher.” [i]
Living in greener areas is good for one's health. One would think this was a no brainer. The actual explanation why this is true is more complex than simply avoiding the outdoors for fear of stepping in “dog mess.”
This study brings to my mind an article by Joan Maloof published in a recent edition of NewScientist: http://www.terrain.org/articles/14/maloof.htm Dr Maloof writes of the Japanese practice of shinrin-yoku, or wood air breathing and wonders how much our attraction to forests comes from the aromatherapy treatment we receive while walking in their midst's. Dr. Maloof writes,
“So what could be in the forest air that makes us feel better? In a study done in the Sierra Nevadas of California, researchers found 120 different chemical compounds—but they could only identify seventy of them! We are literally breathing things we don't understand; which also means, of course, that when we lose these forests, we don't know what we are losing.”
An interesting study on Shinrin-yoku was published back in 1998 in the International Journal of Biometerology.  The study examined the effect of "shinrin-yoku" (forest-air bathing and walking) on blood sugar levels in diabetic patients. Eighty-seven non-insulin-dependent diabetic patients participated. The patients were divided into two parties. They then walked in the forest for 3 km or 6 km according to their physical ability and/or the existence of diabetic complications. The average blood glucose level after forest walking dropped from 179 to 108. The researchers theorized that the forest environment causes changes in hormonal secretion and autonomic nervous functions; walking in a forest environment had other beneficial effects in decreasing blood glucose levels in addition to simply the increased calorie consumption and improved insulin sensitivity. [ii]
The majority of the aromatic compounds given off by trees are classified chemically as monoterpenes. This is interesting as we have been following monoterpene research in relation to cancer treatment for a number of years. Monoterpines are found in the essential oils of many plants. Two of the best known are limonene, found in orange peel and perillyl alcohol found in the essential oils of peppermint, spearmint, sage, cherries and cranberries.
The most interesting recent monoterpene research is Steve Clark's on leukemia. Steve Clark, a professor at the University of Wisconsin Comprehensive Cancer , had his interest triggered when one of his colleagues discovered that monoterpenes inhibited a signaling pathway in breast cancer cells. [iii] The same pathway is involved in leukemia. But when Dr. Clark investigated the effect on leukemia he found that perillyl alcohol affected other pathways than it did in breast cancer cells. Clark focused on chronic myeloid leukemia (CML). In recent years the drug Gleevac has made great advances in treating CML. Clark theorizes that perillyl alcohol might be useful in treating CML patients who don't respond to Gleevac. [iv] [v]
I am still surprised when I realize how much the chemicals in plants affect other animals, including people. It is easy to forget how much we have in common chemically with the plant kingdom. I found myself reacting in initial disbelief when I read recently that cherries are high in melatonin. “But melatonin's our chemical,” I wanted to say. “What's a cherry doing with it?” Well of course plants are interested in knowing whether it's light or dark outside, probably even more than people and many plants use melatonin to communicate this. [vi]
So should we be so surprised to discover that breathing in the smell of greenery or a forest is good for us, or that the stark landscape of our inner cities is unhealthy?
As usual the version of this article posted to our website contains abstracts of the studies mentioned. In addition there are links to the full text of the graffiti, greenery and obesity article as well as Clark 's recent article on leukemia. The website version can be found well right here.... you're already there.
[i] Free full text of article:
BMJ. 2005 Aug 19; [Epub ahead of print]
Graffiti, greenery, and obesity in adults: secondary analysis of European cross sectional survey.
Ellaway A, Macintyre S, Bonnefoy X.
MRC Social and Public Health Sciences Unit, University of Glasgow , Glasgow , G12 8RZ .
[ii] Int J Biometeorol. 1998 Feb;41(3):125-7.
Shinrin-yoku (forest-air bathing and walking) effectively decreases blood glucose levels in diabetic patients.
Ohtsuka Y, Yabunaka N, Takayama S.
Department of Gerontotherapeutics, Hokkaido University School of Medicine, Sapporo , Japan . email@example.com
The influence of "shinrin-yoku" (forest-air bathing and walking) on blood glucose levels in diabetic patients was examined. Eighty-seven (29 male and 58 female) non-insulin-dependent diabetic patients [61 (SEM 1) years old] participated in the present study. Shinrin-yoku was performed nine times over a period of 6 years. The patients were divided into two parties. They then walked in the forest for 3 km or 6 km according to their physical ability and/or the existence of diabetic complications. The mean blood glucose level after forest walking changed from 179 (SEM 4) mg.100 ml-1 to 108 (SEM 2) mg.100 ml-1 (P < 0.0001). The level of glycated haemoglobin A1c also decreased from 6.9 (SEM 0.2)% (before the first shinrin-yoku) to 6.5 (SEM 0.1)% (after the last shinrin-yoku; P < 0.05). Blood glucose values declined by 74 (SEM 9) mg.100 ml-1 and 70 (SEM 4) mg.100 ml-1 after short- and long-distance walking respectively. There was no significant difference between these values. Since the forest environment causes changes in hormonal secretion and autonomic nervous functions, it is presumed that, in addition to the increased calorie consumption and improved insulin sensitivity, walking in a forest environment has other beneficial effects in decreasing blood glucose levels.
PMID: 9531856 [PubMed - indexed for MEDLINE]
[iii] Breast Cancer Res Treat. 2004 Apr;84(3):251-60.
Perillyl alcohol inhibits human breast cancer cell growth in vitro and in vivo.
Yuri T, Danbara N, Tsujita-Kyutoku M, Kiyozuka Y, Senzaki H, Shikata N, Kanzaki H, Tsubura A.
Department of Pathology II, Kansai Medical University , Moriguchi, Osaka , Japan .
The effect of monoterpene perillyl alcohol (POH) on cell growth, cell cycle progression, and expression of cell cycle-regulatory proteins in estrogen receptor (ER)-positive (KPL-1 and MCF-7) and ER-negative (MKL-F and MDA-MB-231) human breast cancer cell lines was examined. POH inhibited cell proliferation in a dose-dependent manner in all cell lines tested. POH at a dose of 500 micro M had a cytostatic effect, in which growth inhibition was due to accumulation of cells in G1-phase. Cell cycle progression was preceded by a decrease in G1 cyclins (cyclin D1 and E), followed by an increase in p21(Cip1/Waf1) and a decrease in proliferating cell nuclear antigen level. Levels of p53 and cyclin A were unchanged. POH at a dose of 75 mg/kg administered intraperitoneally three times a week throughout the entire 6-week experimental period suppressed orthotopically transplanted KPL-1 tumor cell growth and regional lymph node metastasis in a nude mouse system. POH inhibited both ER-positive and -negative human breast cancer cell growth in vitro, and suppressed growth and metastasis in vivo.
PMID: 15026623 [PubMed - indexed for MEDLINE]
[iv] Free Text of full article: http://clincancerres.aacrjournals.org/cgi/reprint/9/12/4494
Clin Cancer Res. 2003 Oct 1;9(12):4494-504.
Anti-leukemia effect of perillyl alcohol in Bcr/Abl-transformed cells indirectly inhibits signaling through Mek in a Ras- and Raf-independent fashion.
Clark SS, Zhong L, Filiault D, Perman S, Ren Z, Gould M, Yang X.
University of Wisconsin Comprehensive Cancer, University of Wisconsin , Madison , Wisconsin 53792 , USA . firstname.lastname@example.org
PURPOSE: Perillyl alcohol (POH) displays preventive and therapeutic activity against a wide variety of tumor models, and it has been suggested that this might be associated with the ability of POH to interfere with Ras prenylation. POH also selectively induces G(1) arrest and apoptosis in Bcr/Abl-transformed hematopoietic cells. Because signaling through Ras is necessary for Bcr/Abl transformation, we examined whether POH induces its anti-leukemia effect by inhibiting Ras signaling. EXPERIMENTAL DESIGN: The ability of POH to inhibit posttranslational farnesylation and signaling from Ras as well as signaling through the Raf-Mek-Erk cascade was examined in Bcr/Abl-transformed and mock-transformed cells and related to the anti-leukemia effect of POH. RESULTS: POH does not affect Ras prenylation or Ras activity, but it blocks signaling downstream of Ras by reversing the state of activation of the Erk kinase, Mek. POH affects Mek activity only when it is added to intact cells. Treatment of either cell lysates or of purified Mek with POH has no effect on Mek activity. Inhibition of the Mek-Erk pathway seems to be related to the POH anti-leukemia effect for the following reasons: (a) the concentration of POH needed to block the Erk pathway, as well the kinetics with which POH inhibits this signaling cascade, both correlate with the anti-leukemia effect of POH; (b) both U0126 (a specific Mek inhibitor) and POH induce similar anti-leukemia effects; and (c) mock-transformed hematopoietic cells are simultaneously resistant to POH anti-leukemia effects and inhibition of the Mek-Erk pathway. CONCLUSION: Blocking Mek is sufficient to induce growth arrest and apoptosis in Bcr/Abl-transformed cells; therefore, POH represents a novel small molecule inhibitor of Mek that might be effective for treating Bcr/Abl leukemias.
PMID: 14555523 [PubMed - indexed for MEDLINE]
[v] Leukemia. 2002 Feb;16(2):213-22.
Antileukemia activity of perillyl alcohol (POH): uncoupling apoptosis from G0/G1 arrest suggests that the primary effect of POH on Bcr/Abl-transformed cells is to induce growth arrest.
Clark SS, Perman SM, Sahin MB, Jenkins GJ, Elegbede JA.
Department of Human Oncology, Oncology and the UW Comprehensive Cancer Center, University of Wisconsin, Madison, WI, USA.
In hematopoietic cells, the Bcr/Abl tyrosine kinase that is encoded by the Philadelphia chromosome translocation both stimulates proliferation and activates an anti-apoptotic program that is associated with a G2/M delay upon exposure to various apoptotic stimuli. We recently reported that the monocyclic monoterpene, perillyl alcohol (POH) selectively induces in Bcr/Abl transformed cells, G0/G1 arrest and apoptosis. Therefore, POH activates anti-proliferative and apoptotic pathways against which the Bcr/Abl kinase does not protect. In this report, we show that in Bcr/Abl-transformed cells, POH induces cytoplasmic acidification, redistribution of phosphatidylserine in the plasma membrane along with DNA fragmentation, all of which can be prevented by the phorbol ester, TPA. The ability of TPA to protect against POH-induced cytotoxicity was blocked by inhibitors of protein kinase C (PKC) and the Na(+)/H(+) antiport. In contrast, TPA does not protect the cells from POH-mediated G0/G1 arrest. While POH inhibits a distal step in the mevalonate biosynthesis pathway, lovastatin, also a potential anticancer agent, inhibits the initial step in this pathway. Not surprisingly, lovastatin also induces G0/G1 arrest and apoptosis in Bcr/Abl-transformed cells, however, TPA protects cells from both apoptosis and G0/G1 arrest caused by lovastatin. Thus, in Bcr/Abl-transformed cells, POH and lovastatin cause growth arrest by different mechanisms. Together, these observations demonstrate that POH-mediated cell cycle arrest precedes apoptosis and raises the possibility that that the primary effect of POH is to induce G0/G1 arrest with apoptosis being a consequence of the growth arrest.
PMID: 11840288 [PubMed - indexed for MEDLINE]
[vi] J Agric Food Chem. 2001 Oct;49(10):4898-902
Detection and quantification of the antioxidant melatonin in Montmorency and Balaton tart cherries (Prunus cerasus).
Burkhardt S, Tan DX, Manchester LC, Hardeland R, Reiter RJ.
Department of Cellular and Structural Biology, University of Texas Health Science Center , Mail Code 7762, 7703 Floyd Curl Drive, San Antonio , Texas 78229-3900 , USA .
The antioxidant melatonin was recently identified in a variety of edible plants and seeds in high concentrations. In plants, as in animals, melatonin is believed to function as a free radical scavenger and possibly in photoperiodism. In this study, melatonin was detected and quantified in fresh-frozen Balaton and Montmorency tart cherries (Prunus cerasus) using high-performance liquid chromatography. Both cherry species contain high levels of melatonin compared to the melatonin concentrations in the blood of mammals. Montmorency cherries (13.46 +/- 1.10 ng/g) contain approximately 6 times more melatonin than do Balaton cherries (2.06 +/- 0.17 ng/g). Neither the orchard of origin nor the time of harvest influenced the amount of melatonin in fresh cherries. The implication of the current findings is that consuming cherries could be an important source of dietary melatonin inasmuch as melatonin is readily absorbed when taken orally. Also, previously published data and the results presented here show that melatonin is not only endogenously produced but also present in the diet.
PMID: 11600041 [PubMed -