Interconnectedness of Everything
Inflammation is not the underlying root of any disease. It is a side effect of a deeper cause. Tinkering with inflammation is tinkering with the immune system. Buzzwords like “anti-cancer”, “anti-viral”, “anti-inflammation” and “immune-boosting” are misleading and offer no information about how various herbs, supplements and pharmaceuticals actually work. Desperate for relief, ill consumers are constantly duped by the supplement industry as they seek easy answers for complex diseases. When the mechanism of a supplement doesn’t match the underlying cause of the immune imbalance, short-term side effects commonly occur. An understanding the mechanisms of aging offers us a glimpse of the potential short-term and long-term side effects that can result from tinkering with the immune system.
When I began studying functional medicine 18 years ago, I was awakened to the then controversial hypothesis that inflammation was the primary driver of many of the diseases of aging. There were hundreds of studies demonstrating the correlation between inflammation and conditions like heart disease, obesity, diabetes, cancer and even aging. As I developed my practice, it was like having magical powers believing that the cause of heart disease was not cholesterol but, in fact, inflammation. Armed with supplements like fish oil, curcumin and boswellia, I felt like Wonder Woman, striking down interleukin 6, NF-kappa B, TNFα and other inflammatory signals that could lead to disease. It wasn’t until I began treating autoimmune and skin disorders that I came to realize that inflammation is not the underlying root of any of these diseases. It’s a side effect of a deeper cause. In fact, suppressing inflammation without understanding its cause is as insane as turning off the fire alarm and going back to bed while the house fills with smoke.
There are four core mechanisms that drive inflammation. This article will explore the most common; when the immune system recognizes something as an invader and launches an attack using inflammatory chemicals as weapons. In science we call this immune system activation by antigen recognition.
The other three (listed below) will be discussed in future posts.
- Over activation of NFKappaB through dietary signaling. Activity of NFKappa B is highly influenced by the presence or absence of insulin[1]. In general, diet doesn’t cause inflammation; it simply acts like a volume control. It isn’t until grossly pathological changes develop through excessive insulin signaling and ROS production that we begin to see the out-of-control inflammation associated with diseases like obesity and diabetes.
- Deranged methylation and acetylation of DNA[2],[3]. Basically methyl groups (from SAMe) and acetyl groups are stuck to DNA to turn it on and off.
- The healing response – the redness, pain and swelling that results from an injury is ultimately an immune response that drives healing. However, repeated injuries, like when high blood pressure repeatedly damages the arteries, will lead to thickening and scarring.
Much of inflammation is nothing more than a side effect of immune activity. A fundamental flaw in our current medical approach to inflammation is the false belief that the immune system is creating inflammation for no reason. As a result, we have an entire industry of herbs, supplements and pharmaceuticals built upon the idea that suppressing inflammation is somehow healing the body. All this despite several large studies demonstrating that conditions associated with inflammation like heart disease[4], diabetes[5] and cancer[6] are mostly driven by external factors. To be clear, unless a true[7] autoimmune condition has developed, the immune system will not act unless there is something triggering it to act. Sometimes we don’t like the results. However, this ancient system that protects us from cancer and invaders is highly intelligent and tightly regulated. The immune system will launch an attack against any critters or substance that it identifies as an invader. These include bacteria, viruses, air pollutants, some metals, environmental contaminants and oxidized LDL cholesterol[8]. It will also attack undigested food proteins like gluten from wheat and lectins from beans. Food sensitivity tests like the ALCAT and Mediator Release Test (MRT) regularly reveal that the immune system will attack virtually any intact food protein or microbe that escapes past the protective gut mucosa (gut lining).
As one example in an ocean of inflammatory immune signals, look at what happens if we tinker with TNFα.
T= “tumor” like cancer
N=“necrosis” like death
Fα=“factor alpha” as a signal category
TNFα is an inflammation weapon produced by certain immune cells to protect us from viruses and cancer. It helps transmit signals from outside a cell to inside a cell’s nucleus where more signals tell the cell to kill itself. In science we call this apoptosis. It is helpful for ensuring that cells that have become cancerous do not survive to divide and grow into a tumor. TNFα also “serve[s] as a first-line defense against influenza virus[9]” and has “strong antiviral activity against many viruses including avian flu and swine flu2”. Upon first glance, it sounds like anything that will increase activity of TNFα can keep you from getting cancer and viruses. Woohoo! In fact, several medicinal mushrooms are promoted as having these anti-cancer and anti-viral properties. Cordyceps[10],[11], Maitake[12], Coriolus[13] and Ganoderma[14], all contain chemicals that increase activity of TNFα*. While this approach can be transformative for someone with a weak immune response, what effects does artificially increasing TNFα have in a healthy person? We know that in high amounts, TNFα causes considerable collateral damage to tissues. It is one of the main participants in diseases like psoriasis[15], ulcerative colitis[16] and rheumatoid arthritis[17]. Moderately high levels are associated with Alzheimer’s disease[18] and even cancer10.
*I suspect that these mushrooms cause an increase in TNFα, not because they have magical properties, but because the immune system sees them as invaders and launches an attack.
Over the long term, does artificially raising TNFα activity accelerate the same degenerative problems that we see with any chronic inflammation? Wouldn’t mildly elevated levels still increase cell turnover, damage tissues, accelerate shortening of telomeres, speed aging and ultimately lead to early senescence*?
(*Senescence is a term used in aging research to describe the end stage of the aging process of a cell, tissue or system. When a cell reaches senescence it can no longer function properly or divide to form new cells. As more cells reach senescence in a given tissue, the more that tissue shrinks and becomes dysfunctional.)
Unless there is a specific reason to artificially stimulate TNF-alpha, it is important to weigh the potential effects of taking any herbs or mushrooms that raise it. Other herbs that stimulate inflammation by raising TNFα include Cistanches, Dipsacus, Echinacea and Psoralea. I have personally seen several patients whose autoimmune conditions were severely exacerbated from taking medicinal mushrooms. They were duped by claims and promises that somehow their condition was a result of a “weak” immune system and that these mushrooms were their salvation. On the other hand, with proper diagnosis, these types of mushrooms can be used as an effective tool when the immune response is too weak. Poor wound healing and recurrent viral infections (like shingles and Epstein Barr) are often caused by a weak immune response. Another scenario where these mushrooms may have benefit is with cancer. I have worked with scores of patients who were doing well months after their doctor prescribed Maitake-D as part of a larger protocol to help the immune system kill cancer cells. (Notice I said “part of a protocol”).
In the ocean of herbs and supplements that are supposed to help us live longer and healthier, how do we know which ones are actually helping? With illness, when the mechanism of a supplement doesn’t match the underlying cause of an immune imbalance short-term side effects commonly occur. What are the less detectable the long-term consequences? Is it possible to accelerate the aging process by inappropriately stimulating the immune system?
[1] Kurtak, K. Dietary and Nutritional Manipulation of the Nuclear Transcription Factors, PPAR’s and SREBP’s,as a Tool for Reversing the Primary Diseases of Premature Death and Aging. Rejuvenation Research 17-2. April 2014. P 140-44.
[2] D. Bayarsaihan Epigenetic Mechanisms in Inflammation J Dent Res. 2011 Jan; 90(1): 9–17. doi: 10.1177/0022034510378683 PMCID: PMC3144097
[3] Stephen B Baylin DNA methylation and gene silencing in cancer. Nature Clinical Practice Oncology (2005) 2, S4-S11 doi:10.1038/ncponc0354. Received 16 August 2005 | Accepted 30 August 2005
[4] Prof Salim Yusuf DPhil,Steven Hawken MSc,Stephanie Ôunpuu PhD,Tony Dans MD,Alvaro Avezum MD,Fernando Lanas MD,Matthew McQueen FRCP,Andrzej Budaj MD,Prem Pais MD,John Varigos BSc,Liu Lisheng MD,on behalf of the INTERHEART Study Investigators Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study
The Lancet – 11 September 2004 ( Vol. 364, Issue 9438, Pages 937-952 )
DOI: 10.1016/S0140-6736(04)17018-9
[5] Dariush Mozaffarian, MD, DrPH; Aruna Kamineni, MPH; Mercedes Carnethon, PhD; Luc Djoussé, MD, ScD; Kenneth J. Mukamal, MD; David Siscovick, MD, MPH. Lifestyle Risk Factors and new Onset Diabetes Mellitus in Older Adults. Arch Intern Med. 2009;169(8):798-807. doi:10.1001/archinternmed.2009.21.
[6] Song Wu, Scott Powers, Wei Zhu & Yusuf A. Hannun. Substantial contribution of extrinsic risk factors to cancer development. Nature (2015) doi:10.1038/nature16166
Received 15 April 2015 Accepted 23 October 2015 Published online 16 December 2015
[7] From experience I have no doubt that many conditions that are diagnosed as “autoimmune” are nothing more than an appropriate immune reaction to an unidentified trigger that has grown out of control. This is commonly seen with leaky gut syndrome, SIBO and dental infections.
[8] Although there are hundreds of studies showing that oxidized LDL elicits inflammation from macrophages, it has never been shown whether this is an immune reaction or a healing response.
[9] Seo SH, Webster RG. Tumor necrosis factor alpha exerts powerful anti-influenza virus effects in lung epithelial cells. J Virol. 2002 Feb;76(3):1071-6.
[10] Test on mononuclear cells Lymphoproliferative, inhibited NK cell activity, phytohemagglutinin response raises IL2, raises TNF-alpha, IL-2 Kuo YC1, Tsai WJ, Shiao MS, Chen CF, Lin CY. Cordyceps sinensis as an immunomodulatory agent. Am J Chin Med. 1996;24(2):111-25.
[11] Jong Seok Lee, Eock Kee Hong. Immunostimulating Activity of the Polysaccharides Isonated from Cordyceps militaris. International Immunopharmacology. Vol 11, Isue 9, September 2011 Pp 1226-1233 doi:10.1016/j.intimp.2011.04.001
[12] Matsui K1, Kodama N, Nanba H. Effects of maitake (Grifola frondosa) D-Fraction on the carcinoma angiogenesis. Cancer Lett. 2001 Oct 30;172(2):193-8.
[13] Cheuk-Lun Lee, Xiaotong Yang, Jennifer Man-Fan Wan. The culture duration affects the immunomodulatory and anticancer effect of polysaccharopeptide derived from Coriolus versicolor. Enzyme and Microbial Technology. Volume 38, Issues 1–2, 3 January 2006, Pages 14–21
[14] Hung-Sen Chena, Yow-Fu Tsaia, Steven Lina, Chia-Ching Lina, Kay-Hooi Khoo, Chun-Hung Lin , , Chi-Huey Won. “Studies on the immuno-modulating and anti-tumor activities of Ganoderma lucidum (Reishi) polysaccharides”. Bioorganic & Medicinal Chemistry Volume 12, Issue 21, 1 November 2004, Pages 5595–5601
[15] Victor FC, Gottlieb AB (2002). “TNF-alpha and apoptosis: implications for the pathogenesis and treatment of psoriasis”. J Drugs Dermatol 1 (3): 264–75. PMID 12851985.
[16] Sands BE1, Kaplan GG The role of in ulcerative colitis.. J Clin Pharmacol. 2007 Aug;47(8):930-41. Epub 2007 Jun 13.
[17] VASANTHI, P., NALINI, G. and RAJASEKHAR, G. (2007), Role of tumor necrosis factor-alpha in rheumatoid arthritis: a review. APLAR Journal of Rheumatology, 10: 270–274. doi: 10.1111/j.1479-8077.2007.00305.x
[18] Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N (2010). “A meta-analysis of cytokines in Alzheimer’s disease”. Biol Psychiatry 68 (10): 930–941. doi:10.1016/j.biopsych.2010.06.012. PMID 20692646.
by 
In the temperate zones of the Earth, late summer into autumn has been a time of celebration in many cultures. This is the time when all creatures breathe a sigh of relief as the hard work of growth slows. The cooler air transforms summer’s searing rays of sunshine into loving, golden warmth. Pregnant with sugar, fruits of flowering plants hang heavy from the branches and dapple the landscape in a mosaic of reds, blues and purples from anthocyanins and carotenoids. On the ground, combinations of lutein and zeaxanthin color the winter squashes of the Cucurbita family with the same oranges and yellows that are revealed as chlorophyll relinquishes its dominion over the foliage.
Colorful pigments that once acted as a beacon for pollinators in an array of colors and hormones[1] assume a new form that will serve as this year’s bridge of survival for numerous species of birds and mammals, including humans.
Over these precious few weeks, concentrated glucose and fructose flow in like the ocean tide. With them, the stomach’s master hormones of appetite flip flop. Ghrelin’s waxing and leptin’s waning[2] impose an ever-rising voracity of appetite that has driven successful survival of species over hundreds of millions of years. Inside the sweet goodness lurks even more treasures. Fresh omega-six oils from seeds and grains give a fresh boost to dwindling eicosanoids that are crucial for cell-to-cell communication. Vitamin E, selenium[3], vitamin C and phytonutrients stand like a levy to ensure the rising tide of inflammation doesn’t breach its banks.
In Traditional Chinese Medicine Theory, this time of year was considered the fifth season associated with the Earth element. Warmth, sunshine, water and Earth have been magically transformed by a billion tiny seeds into a form that passes life’s nourishment unto us. In the Jewish tradition, this season beckons the new year known as Rosh Hashanah.
“Blessed are you, sovereign of the Universe who brings forth bread to the Earth…who has kept us in life, has sustained us and brought us to this season.” Torah
Lurking deep within the cell, all the way down to the nuclear membrane, a sugar-laden surge of insulin nudges a sleeping Goddess from her torpor. 2.1 billion years ago[4],[5] some of the earliest fungi birthed this goddess and time kindly bequeathed her unto humans. In science she is known as SREBP or sterol regulatory elemental binding proteins. She is the one who, as if by magic, signals that transformation of sugar into a form that can be stored for later use as triglycerides[6] and fat[7]. Without her, most animals in the temperate and arctic zones are unlikely to survive even one winter.
Because of SREBP’s, every cell can make its own LDL cholesterol for membrane repair and vitamin D synthesis. However, without a way to supply basic antioxidants to the cell, LDL quickly oxidizes. This transformation from Dr. Jeckel to Mr. Hyde damages everything it touches[8] and is considered to be one of the driving forces of atherosclerosis7. In order to protect her inner world and ensure a constant supply of antioxidants, SREBP must ask for a little help from one of her cousins in the liver, SREBP-1. While most of the cells of the body settle for glucose as an energy source, the liver engages in a more refined taste for fructose. In fact, liver cells are the only ones that can use fructose and its effects are incendiary. Fructose drives rapid production of LDL cholesterol, fats and inflammation in the liver[9],[10]. This preference for fructose acts as a supply chain for the trillions of cells’ insatiable need for antioxidants during times like these. But without SREBP, these antioxidants are useless. She alone is the key master who permits passage of these antioxidants across the cell membrane. Under the dominion of SREBP, the LDL cholesterol receptor rises to the surface of the cell like a fish rising to feed. If it is lucky, LDL cholesterol will land in its mouth. Along for the ride, precious antioxidants like vitamins A, C, and E are granted access to the cell’s inner world[11].
As this season wanes, berries hang dried and scant on the branches. Insulin recedes as the sugar festival comes to a close. The Earth cools. SREBP breathes a deep sigh as her hard work comes to an end. As she falls into her winter nap, she brings many of the creatures of the Earth with her. Only one creature has successfully escaped the dominion of this goddess. Humans innovated to store carbohydrates externally. This consistent supply of sugar drives insulin to ensure that SREBP never sleeps. Her unrelenting state of slavery drives disorders like obesity[12],[13], fatty liver[14], insulin resistance[15] and atherosclerosis[16], [17]. Perhaps this goddess would argue that these are not diseases at all but are phenotypes brought on by depriving her of a proper rest.
[1] Cutler A.J., Krochko J.E. Formation and breakdown of ABA. Trends Plant. Sci. 1999;4:472–478. doi: 10.1016/S1360-1385(99)01497-1
[2] Teff KL, Elliott, SS, Tschop M, Kieffer TJ, Rader D., Heiman M., Townsend RR., Keim NL, D’Alesso D, Havel Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. PJ J Clin Endocrinol Metab. 2004 Jun;89(6):2963-72
[3] Giacomo dugo, Lara La Pera, Donatella Pollicino, marello Saitta. Determination of Selenium Content in Different Types of Seed Oils by Cathodic Stripping Potentiometry (CSP) J. Agric. Food Chem., 2003, 51 (19), pp 5598–5601
[4] Timothy F. Osborne, Peter J. Espenshade Evolutionary Conservation and Adaptation in the Mechanism that Regulates SREBP Action: What a Long Strange tRIP It’s Been. Genes & Dev. 2009. 23: 2578-2591, doi:10.1101/gad.1854309
[5] V Laudet Evolution of the Nuclear Receptor Superfamily: Early Diversification from an Ancestral Orphan Receptor. Journal of Molecular Endocrinology Dec. 1, 1997. 19 2-7-226
[6] Colleen K. Nye Glyceroneogenesis Is the Dominant Pathway for Triglyceride Glycerol Synthesis in Vivo in the Rat The Journal of Biological Chemistry, 283, 27565-27574. October 10, 2008
[7] Hitoshi Shimano, SREBPs: physiology and pathophysiology of the SREBP family. The FEBS Journal 2009 276:3 616-621
[8] Low Density Lipoprotein Can Cause Death of Islet β-Cells by Its Cellular Uptake and Oxidative Modification Miriam Cnop, Jean Claude Hannaert, Annick Y. Grupping, and Daniel G. Pipeleers Endocrinology 2002 143:9 , 3449-3453 http://dx.doi.org/10.1210/en.2002-220273
[9] Zhang C, Chen X, Zhu RM, Zhang Y, Tu T, Wang H., Zhao H, Zhao M, Ji YL, Chen YH, Meng XH, Wei W, Xu DX. “Endoplasmic reticulum stress is involved in hepatic SREBP-1c activation and lipid accumulation in fructose-fed mice.” 2012 Aug 3;212(3):229-40. doi: 10.1016/j.toxlet.2012.06.002. Epub 2012 Jun 12.
“ER stress contributes, at least in part, to hepatic SREBP-1c activation and lipid accumulation in fructose-evoked NAFLD.”
[10] Koo HY, Miyashita M, Cho BH, Nakamura MT. Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus. 2009 Dec 11;390(2):285-9. doi: 10.1016/j.bbrc.2009.09.109. Epub 2009 Sep 30.
“Nuclear SREBP-1 was 2.2 times higher in fructose-fed rats than glucose-fed rats.”
[11] Maret G Traber, Herbert J Kayden “Vitamin E is Delivered to Cells via the High Affinity Receptor for Low-Density Lipoprotein” The American Journal of Clinical Nutrition 40: October 1984, pp 747-51.
[12] Hitoshi Shimano, SREBPs: physiology and pathophysiology of the SREBP family. The FEBS Journal 2009 276:3 616-621
[13] Hitoshi Shimano, SREBPs: physiology and pathophysiology of the SREBP family. The FEBS Journal 2009 276:3 616-621
[14] Moon YA, Liang G, Xie X, Frank-Kamenetsky M, Fitzgerald K, Koteliansky V, Brown MS, Goldstein JL, Horton JD. The Scap/SREBP pathway is essential for developing diabetic fatty liver and carbohydrate-induced hypertriglyceridemia in animals. Cell Metab. 2012 Feb 8;15(2):240-6
[15] Iichiro Shimomura, Robert E. Hammer, James A. Richardson, Shinji Ikemoto, Yuriy Bashmakov, Joseph L. Goldstein,Michael S. Brown
Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev. 1998 October 15; 12(20): 3182–3194.
[16] Karasawa T, Takahashi A, Saito R, Sekiya M, Igarashi M, Iwasaki H, Miyahara S, Koyasu S, Nakagawa Y, Ishii K, Matsuzaka T, Kobayashi K, Yahagi N, Takekoshi K, Sone H, Yatoh S, Suzuki H, Yamada N, Shimano H. Sterol regulatory element-binding protein-1 determines plasma remnant lipoproteins and accelerates atherosclerosis in low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2011 Aug;31(8):1788-95.
[17] Kurtak, K. Dietary and Nutritional Manipulation of the Nuclear Transcription Factors, PPAR’s and SREBP’s, as a Tool for Reversing the Primary Diseases of Premature Death and Aging. Rejuvenation Research 17-2. April 2014. P 140-44.
by 
The only remaining people in the native Ecuadoran village of Agua Santi were women, children and the elderly. There was so little water that no one had bathed or washed their clothes in several weeks. The only food left was fava beans. Most of the men had left home to find work to help feed their families. Patricio, one of the only farmers who still had a trickle of water, remained behind to help supply food for his people and care for his trees and his grandmother. 2010 saw the tipping point of a severe drought that plagued the Chimborazo Province in the heart of Ecuador.
A few years prior, Patricio had lost his two young daughters in a cistern he had built that was intended to supply water to his crops. Since then, his heart’s mission was to reforest Mt. Si Sic, which stood behind his farm. Centuries ago the Spanish had pushed the native people from their land and had destroyed much of the surrounding forests. Patricio believed that if he could restore the forest on the mountain, the rains would return. In his “spare time” he raised native tree saplings and trekked up the mountain with water to plant them. When he began his mission he quickly discovered that planting non-native trees destroyed the quality of the soil. As he overcame a sharp learning curve, he began to understand which trees were native and how to effectively cultivate them. By the time of our meeting he had managed to re-forest scores of acres on Mt. Si Sic.
On his occasional trips into the town of Rio Bamba Patricio would stop at the library and learn a few more English words on the Internet to serve as a bridge between the western world and his native Kichwa. Somewhere along this path he met Jonathan Sparrow, an ethnobotanist who had taught himself to speak Kichwa. Jonathan had been traveling to numerous indigenous villages in Ecuador. His sole purpose was to teach the native people how to support themselves and their communities by protecting their forests. He was succeeding and the people were deeply enthusiastic. Over the previous decades many native communities were seduced into working for companies who would clear-cut the forests to harvest the wood and make room to grow coffee and other crops. Over the years, Jonathan had helped Patricio carry out his mission and they had become close friends.
We were a small group of women healers from the World Healing Exchange and Jonathan was our guide. This is a branch of Acupuncturists Without Borders whose purpose is to help heal trauma in communities who have been stricken by disaster. Until the psychological aspect of trauma has healed, it hinders its victims from moving forward and participating in the healing of themselves and their communities. Our purpose was to reach out to these indigenous villages and exchange wisdom with their native healers while helping them to move through these difficult times. The remaining indigenous people of Agua Santi were experiencing deep loss and trauma. We performed an acupuncture protocol for trauma called, NADA, on the entire village. Afterwards, the village gave us fava beans (I still can’t believe they fed us), and insisted that we come with them to the top Mt. Si Sic.
At age 75, Margarita and her friends from Agua Santi ascended Mt. Si Sic in their brilliant native indigos, reds and purples, as if they were fairies floating effortlessly up through the young secondary forest. We struggled to keep up as they guided us, eager to show us something. When we arrived at the top, Margarita and her elderly friends were lying on the forest floor laughing and throwing pebbles at anyone who dozed off in the filtered sunlight. A few children played on rock outcroppings. When everyone finally arrived at the top we all walked together towards the mysterious project. It was a cistern that the community had been building that would supply water when the rains came again. Jonathan was there to help them with the final construction and afterwards there was a joyous ceremony with chanting and blessings.
The following morning we woke to find that Margarita and many others from Agua Santi had walked several miles from their village to the monastery where we were staying on the outskirts of Rio Bamba. Patricio was there too. Their smiles were as bright as the sun and they wanted to come with us. The Ecuadorian government had kindly provided us with a small bus for traveling through the country and we managed to pack in everyone. No one in Agua Santi owned a car. As I understood it, for some, this was their first ride in a motor vehicle.
There is a certain odor that a person develops when they haven’t been able to bathe or wash their clothes for months. Yes, their drought was that bad. I never would have believed I could associate such an odor with pure joy. However, riding in such close quarters on what would become a magical day, that particular odor permeated everything. Afterwards, I could never bring myself to wash the blouse I wore that day. I keep it in a plastic bag in hopes that it will never lose that beautiful, loving scent.
That morning we visited and treated another village that was even worse off than Agua Santi. It was more populated and the people were despondent. This is a story for another time but I want to mention something that I will never forget where we convened in their town hall. While we were there, one of the native people stood up and screamed something in Kichwa. He was clearly angry. Jonathan translated “You tell your people to take back their poison seeds and give us back our own! You brought us these seeds that produce only one time and then they are barren!” Jonathan explained that some people from a corporation had come in and shown the amazing plants they could grow from GMO seeds. They gave them the seeds in exchange for their own. They failed to mention that they were hybrids. The following year, when the people planted the seeds from these crops they found that none of them could reproduce. These poor people wasted their energy and their water on planting seeds that could never sprout. This was a dangerous scenario that threatened their food, their animal’s food and their ability to survive.
We left the village that afternoon and Jonathan mentioned that there was a hot spring about an hour away. No one from Agua Santi had ever been to a hot spring. We went and soaked in the healing waters of San Francesco. I’ve never seen such joy pouring from other human beings. These beautiful people, who were surviving a severe drought, hadn’t bathed in weeks were splashing and playing and laughing for hours. The elderly ladies unbraided their hair that reached past their wastes and let it float and swirl in the water. As the day came to a close, the waters were drained out of the pools. The people of Agua Santi all gathered in the main pool that had a likeness of St. Francesco. In it, they all held hands and prayed and chanted. As the water drained out, they moved closer and closer together so they could remain in the water. They held hands and said prayers until the very last drop had drained out.
Several days later, when I arrived back in civilization, I came to realize that this day, with these people whose drought-stricken village bore the namesake, Saint of Water, happened to be International Water Day.
by In the temperate zones of the Earth, late summer into autumn has been a time of celebration in many cultures. This is the time when all creatures breathe a sigh of relief as the hard work of growth slows. The cooler air transforms summer’s searing rays of sunshine into loving, golden warmth. Pregnant with sugar, fruits of flowering plants hang heavy from the branches and dapple the landscape in a mosaic of reds, blues and purples from anthocyanins and carotenoids. On the ground, combinations of lutein and zeaxanthin color the winter squashes of the Cucurbita family with the same oranges and yellows that are revealed as chlorophyll relinquishes its dominion over the foliage.
Colorful pigments that once acted as a beacon for pollinators in an array of colors and hormones[1] assume a new form that will serve as this year’s bridge of survival for numerous species of birds and mammals, including humans.
Over these precious few weeks, concentrated glucose and fructose flow in like the ocean tide. With them, the stomach’s master hormones of appetite flip flop. Ghrelin’s waxing and leptin’s waning[2] impose an ever-rising voracity of appetite that has driven successful survival of species over hundreds of millions of years. Inside the sweet goodness lurks even more treasures. Fresh omega-six oils from seeds and grains give a fresh boost to dwindling eicosanoids that are crucial for cell-to-cell communication. Vitamin E, selenium[3], vitamin C and phytonutrients stand like a levy to ensure the rising tide of inflammation doesn’t breach its banks.
In Traditional Chinese Medicine Theory, this time of year was considered the fifth season associated with the Earth element. Warmth, sunshine, water and Earth have been magically transformed by a billion tiny seeds into a form that passes life’s nourishment unto us. In the Jewish tradition, this season beckons the new year known as Rosh Hashanah.
“Blessed are you, sovereign of the Universe who brings forth bread to the Earth…who has kept us in life, has sustained us and brought us to this season.” Torah
Lurking deep within the cell, all the way down to the nuclear membrane, a sugar-laden surge of insulin nudges a sleeping Goddess from her torpor. 2.1 billion years ago[4],[5] some of the earliest fungi birthed this goddess and time kindly bequeathed her unto humans. In science she is known as SREBP or sterol regulatory elemental binding proteins. She is the one who, as if by magic, signals that transformation of sugar into a form that can be stored for later use as triglycerides[6] and fat[7]. Without her, most animals in the temperate and arctic zones are unlikely to survive even one winter.
Because of SREBP’s, every cell can make its own LDL cholesterol for membrane repair and vitamin D synthesis. However, without a way to supply basic antioxidants to the cell, LDL quickly oxidizes. This transformation from Dr. Jeckel to Mr. Hide damages everything it touches[8] and is considered to be one of the driving forces of atherosclerosis7. In order to protect her inner world and ensure a constant supply of antioxidants, SREBP must ask for a little help from one of her cousins in the liver, SREBP-1. While most of the cells of the body settle for glucose as an energy source, the liver engages in a more refined taste for fructose. In fact, liver cells are the only ones that can use fructose and its effects are incendiary. Fructose drives rapid production of LDL cholesterol, fats and inflammation in the liver[9],[10]. This preference for fructose acts as a supply chain for the trillions of cells’ insatiable need for antioxidants during times like these. But without SREBP, these antioxidants are useless. She alone is the key master who permits passage of these antioxidants across the cell membrane. Under the dominion of SREBP, the LDL cholesterol receptor rises to the surface of the cell like a fish rising to feed. If it is lucky, LDL cholesterol will land in its mouth. Along for the ride, precious antioxidants like vitamins A, C, and E are granted access to the cell’s inner world[11].
As this season wanes, berries hang dried and scant on the branches. Insulin recedes as the sugar festival comes to a close. The Earth cools. SREBP breathes a deep sigh as her hard work comes to an end. As she falls into her winter nap, she brings many of the creatures of the Earth with her. Only one creature has successfully escaped the dominion of this goddess. Humans innovated to store carbohydrates externally. This consistent supply of sugar drives insulin to ensure that SREBP never sleeps. Her unrelenting state of slavery drives disorders like obesity[12],[13], fatty liver[14], insulin resistance[15] and atherosclerosis[16], [17]. Perhaps this goddess would argue that these are not diseases at all but are phenotypes brought on by depriving her of a proper rest.
[1] Cutler A.J., Krochko J.E. Formation and breakdown of ABA. Trends Plant. Sci. 1999;4:472–478. doi: 10.1016/S1360-1385(99)01497-1
[2] Teff KL, Elliott, SS, Tschop M, Kieffer TJ, Rader D., Heiman M., Townsend RR., Keim NL, D’Alesso D, Havel Dietary fructose reduces circulating insulin and leptin, attenuates postprandial suppression of ghrelin, and increases triglycerides in women. PJ J Clin Endocrinol Metab. 2004 Jun;89(6):2963-72
[3] Giacomo dugo, Lara La Pera, Donatella Pollicino, marello Saitta. Determination of Selenium Content in Different Types of Seed Oils by Cathodic Stripping Potentiometry (CSP) J. Agric. Food Chem., 2003, 51 (19), pp 5598–5601
[4] Timothy F. Osborne, Peter J. Espenshade Evolutionary Conservation and Adaptation in the Mechanism that Regulates SREBP Action: What a Long Strange tRIP It’s Been. Genes & Dev. 2009. 23: 2578-2591, doi:10.1101/gad.1854309
[5] V Laudet Evolution of the Nuclear Receptor Superfamily: Early Diversification from an Ancestral Orphan Receptor. Journal of Molecular Endocrinology Dec. 1, 1997. 19 2-7-226
- [6] Colleen K. Nye Glyceroneogenesis Is the Dominant Pathway for Triglyceride Glycerol Synthesis in Vivo in the Rat The Journal of Biological Chemistry, 283, 27565-27574. October 10, 2008
[7] Hitoshi Shimano, SREBPs: physiology and pathophysiology of the SREBP family. The FEBS Journal 2009 276:3 616-621
[8] Low Density Lipoprotein Can Cause Death of Islet β-Cells by Its Cellular Uptake and Oxidative Modification Miriam Cnop, Jean Claude Hannaert, Annick Y. Grupping, and Daniel G. Pipeleers Endocrinology 2002 143:9 , 3449-3453 http://dx.doi.org/10.1210/en.2002-220273
[9] Zhang C, Chen X, Zhu RM, Zhang Y, Tu T, Wang H., Zhao H, Zhao M, Ji YL, Chen YH, Meng XH, Wei W, Xu DX. “Endoplasmic reticulum stress is involved in hepatic SREBP-1c activation and lipid accumulation in fructose-fed mice.” 2012 Aug 3;212(3):229-40. doi: 10.1016/j.toxlet.2012.06.002. Epub 2012 Jun 12.
“ER stress contributes, at least in part, to hepatic SREBP-1c activation and lipid accumulation in fructose-evoked NAFLD.”
[10] Koo HY, Miyashita M, Cho BH, Nakamura MT. Replacing dietary glucose with fructose increases ChREBP activity and SREBP-1 protein in rat liver nucleus. 2009 Dec 11;390(2):285-9. doi: 10.1016/j.bbrc.2009.09.109. Epub 2009 Sep 30.
“Nuclear SREBP-1 was 2.2 times higher in fructose-fed rats than glucose-fed rats.”
[11] Maret G Traber, Herbert J Kayden “Vitamin E is Delivered to Cells via the High Affinity Receptor for Low-Density Lipoprotein” The American Journal of Clinical Nutrition 40: October 1984, pp 747-51.
[12] Hitoshi Shimano, SREBPs: physiology and pathophysiology of the SREBP family. The FEBS Journal 2009 276:3 616-621
[13] Hitoshi Shimano, SREBPs: physiology and pathophysiology of the SREBP family. The FEBS Journal 2009 276:3 616-621
[14] Moon YA, Liang G, Xie X, Frank-Kamenetsky M, Fitzgerald K, Koteliansky V, Brown MS, Goldstein JL, Horton JD. The Scap/SREBP pathway is essential for developing diabetic fatty liver and carbohydrate-induced hypertriglyceridemia in animals. Cell Metab. 2012 Feb 8;15(2):240-6
[15] Iichiro Shimomura, Robert E. Hammer, James A. Richardson, Shinji Ikemoto, Yuriy Bashmakov, Joseph L. Goldstein,Michael S. Brown
Insulin resistance and diabetes mellitus in transgenic mice expressing nuclear SREBP-1c in adipose tissue: model for congenital generalized lipodystrophy. Genes Dev. 1998 October 15; 12(20): 3182–3194.
[16] Karasawa T, Takahashi A, Saito R, Sekiya M, Igarashi M, Iwasaki H, Miyahara S, Koyasu S, Nakagawa Y, Ishii K, Matsuzaka T, Kobayashi K, Yahagi N, Takekoshi K, Sone H, Yatoh S, Suzuki H, Yamada N, Shimano H. Sterol regulatory element-binding protein-1 determines plasma remnant lipoproteins and accelerates atherosclerosis in low-density lipoprotein receptor-deficient mice. Arterioscler Thromb Vasc Biol. 2011 Aug;31(8):1788-95.
[17] Kurtak, K. Dietary and Nutritional Manipulation of the Nuclear Transcription Factors, PPAR’s and SREBP’s, as a Tool for Reversing the Primary Diseases of Premature Death and Aging. Rejuvenation Research 17-2. April 2014. P 140-44.
by Phenotype (fē-nō-tīp)
noun
The net result of the interaction of an organism’s genes with its environment.
In 1953, Watson and Crick’s discovery of DNA was a beacon of hope for understanding what causes human disease. Since then science and medicine have invested billions in research and man hours under the premise and promise that understanding our genetic code would lead us to answers and cures for the leading causes of disease and death. To our surprise, the results have not been so straightforward. As we’ve gained more and more information about our genetic programming, we’ve discovered that genetics plays only a small role in the development of many of the leading causes of chronic disease and premature death. Our antiquated belief that we are destined to fall victim to a disease that ended the life of our parents and/or grandparents has given way to the sometimes difficult realization that we have more influence over the future of our health and our lifespan than we could have imagined.
As more and more research has come online, we’ve discovered that many human diseases are largely a result of external factors that are potentially under our control. A study published in 2004 in The Lancet followed over 15,000 people assessing risk factors for heart attack. The authors identified nine non-genetic risk factors that “collectively accounted for 90-94% of cardiovascular disease and had the potential to prevent the majority of premature myocardial infarction1”. These risk factors were composed of external influences that can all be eliminated including “Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity[i]”.
A study appearing in JAMA in 2008 on 4883 people over the age of sixty-five concluded that 90% of DM2 cases are preventable using 5 lifestyle changes. Diabetes-related risk factors include physical activity level, dietary habits, adiposity, alcohol use, and smoking habits[ii].
As our understanding deepens, it is becoming apparent that perhaps these are not diseases at all but in fact what we call phenotypes.
Since 1998, the statistics regarding cancer risk, which were studied separately by the NIH and WHO, have remained surprisingly steady. Despite thousands of new studies every year the figures stood at approximately 80% environmental (a scientific term for external factors) and 20% genetic. This was concurred in 2014 by The American Cancer Society saying, “environmental factors (as opposed to heredity factors) account for an estimated 75%-80% of cancer cases and deaths in the US[iii]. On January 2nd 2015 this assessment came crashing down with the controversial Science article by Cristian Tomasette and Bert Vogelstein titled “Variation in Cancer Risk Among Tissues Can Be Explained by the Number of Stem Cell Division”[iv]. This was an elegant, groundbreaking study that shined a light on the novel idea that some cancers simply occur because of random mutations during stem cell division. Suddenly, part of the 80% environmental aspect had to be redefined. The authors’ unfortunate choice to assign a new value to the environmental influence in the absence of adequate data parameters was incendiary across the media and scientific community. Six of the top eleven most frequently occurring cancer types were not included in this study. Interestingly, each of the excluded cancer types have a huge body of scientific evidence demonstrating that each of them is highly influenced by environmental factors. Among these cancers were prostate, breast, uterine, urinary bladder, kidney and Non Hodgkin’s Lymphoma, collectively, responsible for nearly 20% or 1/5 of cancer deaths in the US in 2014 and their incidence rate an even higher contribution3. The environmental factors that influence their development include infectious agents[v], endogenous[vi] and exogenous hormones, xenobiotic compounds[vii], certain heavy metals[viii], certain pharmaceuticals, specific industrial and organic chemicals[ix], alcohol consumption[x], glycemic control[xi], and aflatoxin[xii].
One reason the scientific community raised such a fuss about the “bad luck” cancer study was that an inordinate amount of funding and resources is already dedicated to the diagnosis and treatment of cancer. The same goes for many other “diseases” including heart disease and diabetes. After all, each one forms a massive economic base that generates billions of dollars annually. Research funding directed towards the understanding and true prevention of these diseases contributes very little to monthly recurring revenues. Instead, it represents an ominous threat to the economic base of the medical industry as well as any industry whose products might be identified as a risk. Despite the hurdles, advances in our understanding of the processes that create these “diseases” has accelerated so fast that it has created a growing chasm where science and medicine no longer overlap but have diverged. The statistics about the environmental influences on “disease” have been well known in the scientific community for at least 15 years. However, they are poorly acknowledged by the medical industry and, as a result, have remained clandestine to the general public. Chemicals aside, imagine if society truly understood how they could prevent diabetes or delay the onset of heart disease simply by adopting a regimen of glycemic control as described in the studies above. What if it was not based on a drug but was based on reducing their consumption of excess sugar? This one change would have massive reverberations through multiple industries. On one side, there would be reduced “need” for medical services that manage the entire sequela of diseases that are known to be caused by poor glycemic control. This would translate into reduced doctor visits, reduced “need” for pharmaceuticals, fewer hospitalizations, fewer surgeries, lower consumption medical supplies, reduced need for assisted living and in home care, reduction of insurance costs etc. On the other side the industrial farming and food complex would also be widely affected. This includes farming equipment, GPS equipment, chemical fertilizers, pesticides, herbicides, fungicides, GMO seeds, all sugar-laden products, packaging, transportation and distribution, fuel consumption etc. As you can see, a significant base of the economy relies on a mutualistic relationship between Big Farma and Big Pharma. The current medical paradigm actually benefits from environmental problems and generally relegates efforts to fix this to the realm of environmental fundamentalism and quackery.
At what point do we embrace our responsibility of removing the known causes of disease? There are already billions of dollars and man-hours wasted on researching and treating diseases that are created by humans literally poisoning themselves. What is the sense? To continue to protect economic interests cloaked inside a societal dietary lexicon that has been hijacked by mass manipulation of naturally occurring, animalistic addictions through marketing, food additives and advertising? We must focus on removing the factors that create these disease phenotypes. Once this illusion has been cleared we can direct our resources towards novel drugs and therapies that will do the most good. Image a healthy, thriving society where disabled life expectancy is a thing of the past. Where companies and organizations like SENS, Calico and Human Longevity Inc. create drugs that don’t depend on illness but address the factors that are not under our control to produce meaningful lasting advances in health and longevity.
[i] Prof Salim Yusuf DPhil,Steven Hawken MSc,Stephanie Ôunpuu PhD,Tony Dans MD,Alvaro Avezum MD,Fernando Lanas MD,Matthew McQueen FRCP,Andrzej Budaj MD,Prem Pais MD,John Varigos BSc,Liu Lisheng MD,on behalf of the INTERHEART Study Investigators Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study
The Lancet – 11 September 2004 ( Vol. 364, Issue 9438, Pages 937-952) DOI: 10.1016/S0140-6736(04)17018-9
[ii] Dariush Mozaffarian, MD, DrPH; Aruna Kamineni, MPH; Mercedes Carnethon, PhD; Luc Djoussé, MD, ScD; Kenneth J. Mukamal, MD; David Siscovick, MD, MPH. Lifestyle Risk Factors and new Onset Diabetes Mellitus in Older Adults. Arch Intern Med. 2009;169(8):798-807. doi:10.1001/archinternmed.2009.21.
[iii] [iii] ACS (2014). Cancer Facts & Figures 2014, Atlanta. American Cancer Society, 2014. Available at: http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf
[iv] Cristian Tomasetti, Bert Vogelstein. Variation in Cancer Risk Among Tissues Can Be Explained by the Number of Stem Cell Divisions. Science 2 January 2015 Vol. 347 no. 6217 pp. 78-81. DOI:10.1126/science.1260825
[v] Yidya Vedham Ph. D., Mukesh Verma Ph. D. Cancer-Assoicated Infectious Agents and Epigenetic Regulation Cancer Epigenetics Methods in Molecular Biology Nov. 8, 2014 Vol. 1238, pp333-354 Doi: 10.1007/978-1-4939-1804-1_18
[vi] Tim Key; Endogenous Hormones Breast Cancer Collaborative Group Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies. Steroids. Oct. 7, 2014. Doi: 10.1016/j.steroids.2014.09.001
[vii] Hye-Rim Lee; Kyung-A Hwang; Kyung-Chul Choi. The estrogen receptor signaling pathway activated by phthalates is linked with transforming growth factor-β in the progression of LNCaP prostate cancer models. International Journal of Oncology. May 22, 2014. Pp595-602 Doi: 10.3892/ijo.2014.2460
[viii] García-Lestón, J; Roma-Torres, J; Vilares, M; Pinto, R; Prista, J; Teixeira, JP; Mayan, O; Conde, J; Pingarilho, M; Gaspar, JF; Pásaro, E; Méndez, J; Laffon, B. Genotoxic effects of occupational exposure to lead and influence of polymorphisms in genes involved in lead toxicokinetics and in DNA repair. Environ Int, 2012 vol. 43 pp. 29-36
[ix] Guo, H; Bassig, BA; Lan, Q; Zhu, Y; Zhang, Y; Holford, TR; Leaderer, B; Boyle, P; Qin, Q; Zhu, C; Li, N; Rothman, N; Zheng, T. Polymorphisms in DNA repair genes, hair dye use, and the risk of non-Hodgkin lymphoma. Cancer Causes Control, 2014 vol. 25(10) pp. 1261-70
[x] Qian Zhong, Ganggang Shi, Yanmei Zhang, Lei lu, Daniel Levy, Shuping Zhong. Alteration of BRCA1 Expression Affects Alcohol-induced Transcription of RNA Pol III-Dependent Genes. Gene Vol 556, Issue 1, Feb. 1, 2015 74-79.
[xi] Juhyun Park; Sung Yong Cho; Young Ju Lee; Seung Bae Lee; Hwancheol Son; Hyeon Jeong. Poor Glycemic Control of Diabetes Mellitus Is Associated with Higher Risk of Prostate Cancer Detection in a Biopsy Population. PLOS Sept. 18, 2014. Doi: 10.1371/journal.pone.0104789
[xii] Xi-Dai Long; Dong Zhao; Xiao-Qiang Mo; Chao Wang; Xiao-Ying Huang; Jin-Guang Yao; Yun Ma; Zhong-Hua Wei; Min Liu; Li-Xiao Zeng; Jian-Jun Zhang; Feng Xue; Bo Zhai; Qiang Xia. Genetic Polymorphisms in DNA Repair Genes XRCC4 and XRCC5 and Aflatoxin B1–related Hepatocellular Carcinoma. Epidemiology Sept 2013, Vol. 24 Issue 5 pp. 671-81. Doi: 10.1097/EDE.0b013e31829d2744
by In follow up to my previous post outlining concerns and conflicts to the recent “Bad Luck” cancer study, here is a technical article that I submitted to the journal Science. For whatever reasons, they did not want to publish it. Some of the original misinterpretations were brought about by the news editor’s summary. Here is my original manuscript complete with references for the conflicts between conclusions and the study parameters.
This is a game changing study and its wording is of delicate importance. Previous to this study, the NIH and CDC had concluded that 85-90% of cancer cause is due to external factors with only a small percentage being attributed to genetics. Despite this, an inordinate amount of funding has been dedicated to detection and treatment instead of prevention. This study has the power to influence how much energy, funding and resources are dedicated to understanding and eliminating the environmental (external) causes of cancer.
Acknowledgements:
Deepest gratitude to Rebe Feraldi MS, LCACP and Jessee Carrato for their valuable insights and also to Rebe for her time to do a thorough review.
Rebe and I subsequently submitted a letter to Science asking for clarification.
____________________
Abstract:
The recent study, Variation in Cancer Risk Among Tissues Can Be Explained by the Number of Stem Cell Divisions. , published in the January 2, 2015 edition of Science by Cristian Tomasette and Bert Vogelstein elegantly shines light on the previously overlooked notion that many cancer types arise randomly from errors during stem cell divisions.
However, as outlined below, there is a significant dissonance between the study’s data parameters and the statements and conclusions set forth in the study’s title and abstract. As a member of (American Association for the Advancement of Science) AAAS, I feel it is in the spirit of science to demand clear, objective articles whose data and conclusions are congruous and are not overtly vulnerable to misinterpretation by the vast majority of the media, science writers, and the public. Of further concern, these statements could be deceiving for those making informed decisions regarding research funding and public policy.
The primary aspect of the study data parameters which lacks congruity with the study conclusions and abstract is as follows: Six of the top eleven most frequently occurring cancer types were not included in this study and are thus, not reflected in the study conclusions. Among these cancers are: prostate, breast, uterine, urinary bladder, kidney and Non Hodgkin’s Lymphoma, collectively, responsible for nearly 20% or 1/5 of cancer deaths in the US in 2014 and their incidence rate an even higher contribution.[1] There is a substantial body of evidence demonstrating that each of these omitted cancer types is highly influenced by a variety of environmental factors. These environmental factors include infectious agents[2], endogenous[3] and exogenous hormones, xenobiotic compounds[4], certain heavy metals[5], certain pharmaceuticals, specific industrial and organic chemicals[6], alcohol consumption[7], glycemic control[8], and aflatoxin[9]. Per the American Cancer Society (ACS), “environmental factors (as opposed to heredity factors) account for an estimated 75%-80% of cancer cases and deaths in the US.”[10] Although we may eventually find that these environmental factors drive accelerated “random” error events, it is not possible to draw an objective, statistically meaningful conclusion about environmental and heredity vs. “random” influences on cancer as a whole based on the limited data parameters set forth in this study.
Although the aforementioned cancers types (excluded from the study) are presumably part of the one-third of “tissues [that] were not included in [the] analysis”12, their predominance represents a substantial and statistically significant percentage of cancers in the US. It is understandable that “the requisite parameters were not found in the literature or [their] estimation was difficult to derive”12. However, in light of these major exclusions, the conclusions drawn by the authors in the title and in the abstract of the paper should reflect this gross exclusion. Because the exclusion is not highlighted, the stated study conclusions are ambiguous and, as we have seen in the media, are vulnerable to misinterpretation.
Furthermore, the random cancer incidents demonstrated in the study do not parallel the incidence of various cancer types reported by the CDC and NIH. In some cases, like lung and colorectal cancer, they are flip-flopped. This suggests that influences exist outside of the random events like immunity[11] and well-known tumor suppressor genes, which are not accounted for in the study. The article should clarify that the study conclusion merely represents a statistical probability of a random cancer cell events in a given tissue type over a lifetime but does not represent the ultimate fate of any cancer type or cell. The data presented from the study does not provide sufficient evidence for the following statement in the abstract:
“These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions. The majority is due to “bad luck,” that is, random mutations arising during DNA replication in normal, noncancerous stem cells. This is important not only for understanding the disease but also for designing strategies to limit the mortality it causes.[12]”
Did the authors intend that their conclusion was based only on “tissues” that were included in their study? Or were they implying that “only one third of [all] cancer risk is attributable to environmental factors or inherited predispositions?12” Below is a sampling from hundreds of various headlines from six prestigious media organizations that understandably misinterpreted the conclusion of the study article.
******
“Most cancers are ’caused by bad luck – not lifestyle’: Scientists claim 65% of cases are down to random mistakes in genes that we can do nothing about” Jenny Hope of the Daily Mail Jan. 1 2015
“Two-Thirds of Cancer Due to Bad Luck, Study Finds” by Mary Elizabeth Dallas of CBS News reported Jan. 1 2015
“Most cancers are caused by bad luck not genes or lifestyle, scientists say.” By Sara Knapton for the Telegraph Jan. 1 2015
“Bad luck of random mutations plays predominant role in cancer”. Science Daily Jan. 1 2015
“Scientists: Random Gene Mutations Primary Cause of Most Cancer” by Ben Brumfield on CNN
“Biological bad luck blamed in two-thirds of cancers” by Will Dunham of Reuters
******
In addition to the ambiguity of the abstract, the title implies the study is based on overall cancer risk. It would be more accurate to change the wording from “cancer risk” to “some cancer types”.
Of further concern, the authors also make recommendations that could influence the direction and funding of research and public policy. Because of the excluded types of cancer and overall data, the following statement from the article is not scientifically objective and should be removed or clarified:
“Moreover, we show that these stochastic influences are in fact the major contributors to cancer overall, often more important than either hereditary or external environmental factors.”
The authors go on to conclude that,
“These results suggest that only a third of the variation in cancer risk among tissues is attributable to environmental factors or inherited predispositions.”
Although compelling, it is premature to assign exact figures and conclusions based on such limited data.
Ultimately, because of its limited data parameters, this study lacks the merit necessary for forming decisions around research funding and public policy. The broad statements in this article could be misinterpreted by non-science policy makers potentially leading to uninformed decisions about a wide range of issues from allocation of research funds to public health recommendations.
Because the media headlines were so grossly misinterpreted and misleading to the public, corrections and clarifications should be made available as a press release. This act would be in the interest of the integrity of the scientific community and in good faith to the non-science public.
[1] Based on calculations from statistical data in ACS (2014).
[2] Yidya Vedham Ph. D., Mukesh Verma Ph. D. Cancer-Assoicated Infectious Agents and Epigenetic Regulation Cancer Epigenetics Methods in Molecular Biology Nov. 8, 2014 Vol. 1238, pp333-354 Doi: 10.1007/978-1-4939-1804-1_18
[3] Tim Key; Endogenous Hormones Breast Cancer Collaborative Group Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies. Steroids. Oct. 7, 2014. Doi: 10.1016/j.steroids.2014.09.001
[4] Hye-Rim Lee; Kyung-A Hwang; Kyung-Chul Choi. The estrogen receptor signaling pathway activated by phthalates is linked with transforming growth factor-β in the progression of LNCaP prostate cancer models. International Journal of Oncology. May 22, 2014. Pp595-602 Doi: 10.3892/ijo.2014.2460
[5] García-Lestón, J; Roma-Torres, J; Vilares, M; Pinto, R; Prista, J; Teixeira, JP; Mayan, O; Conde, J; Pingarilho, M; Gaspar, JF; Pásaro, E; Méndez, J; Laffon, B. Genotoxic effects of occupational exposure to lead and influence of polymorphisms in genes involved in lead toxicokinetics and in DNA repair. Environ Int, 2012 vol. 43 pp. 29-36
[6] Guo, H; Bassig, BA; Lan, Q; Zhu, Y; Zhang, Y; Holford, TR; Leaderer, B; Boyle, P; Qin, Q; Zhu, C; Li, N; Rothman, N; Zheng, T. Polymorphisms in DNA repair genes, hair dye use, and the risk of non-Hodgkin lymphoma. Cancer Causes Control, 2014 vol. 25(10) pp. 1261-70
[7] Qian Zhong, Ganggang Shi, Yanmei Zhang, Lei lu, Daniel Levy, Shuping Zhong. Alteration of BRCA1 Expression Affects Alcohol-induced Transcription of RNA Pol III-Dependent Genes. Gene Vol 556, Issue 1, Feb. 1, 2015 74-79.
[8] Juhyun Park; Sung Yong Cho; Young Ju Lee; Seung Bae Lee; Hwancheol Son; Hyeon Jeong. Poor Glycemic Control of Diabetes Mellitus Is Associated with Higher Risk of Prostate Cancer Detection in a Biopsy Population. PLOS Sept. 18, 2014. Doi: 10.1371/journal.pone.0104789
[9] Xi-Dai Long; Dong Zhao; Xiao-Qiang Mo; Chao Wang; Xiao-Ying Huang; Jin-Guang Yao; Yun Ma; Zhong-Hua Wei; Min Liu; Li-Xiao Zeng; Jian-Jun Zhang; Feng Xue; Bo Zhai; Qiang Xia. Genetic Polymorphisms in DNA Repair Genes XRCC4 and XRCC5 and Aflatoxin B1–related Hepatocellular Carcinoma. Epidemiology Sept 2013, Vol. 24 Issue 5 pp. 671-81. Doi: 10.1097/EDE.0b013e31829d2744
[10] ACS (2014). Cancer Facts & Figures 2014, Atlanta. American Cancer Society, 2014. Available at: http://www.cancer.org/acs/groups/content/@research/documents/webcontent/acspc-042151.pdf
[11] Junko Kishikawa, Kazushige Kawai, Nelson Tsuno, Hironori Yamaguchi, Soichiro Ishihara, Eiji Sunami, Toshiaki Watanabe. Characteristics and Pronosis of Colorectal Cancer Assoicated with Rheumatic Disease. International Surgery, Dec. 30, 2014 , Doi: 10.9738/INTSURG-D-14-00154.1
[12] Cristian Tomasetti, Bert Vogelstein. Variation in Cancer Risk Among Tissues Can Be Explained by the Number of Stem Cell Divisions. Science 2 January 2015 Vol. 347 no. 6217 pp. 78-81. DOI:10.1126/science.1260825
Acknowledgements:
Deepest gratitude to Rebe Feraldi MS, LCACP and Jessee Carrato for their valuable insights and also to Rebe for her time to do a thorough review.
by A few years ago there was a little-known debate going on in the world of life extension and anti-aging about not eating eggs. Surprisingly this had nothing to do with cholesterol. Instead, the concern was that eggs are high in the amino acid methionine which was shown to accelerate aging…or more precisely, limiting methionine was shown to possibly extend lifespan. Life Extension has a good summary of this research without having to sift through PubMed. At the time I was well into the process of creating the field of Longevity Nutrition. After some investigating, I published this post discussing all of the wonderful health benefits of eggs and the caveats of methionine restriction with regards to life extension. Now that we know that My favorite part of the whole article discusses how the high concentration of methionine likely acts as a signal for fecundity as it travels through the entire food web. Here is a great article that is scientifically accurate discussing the health benefits of eggs that was recently published in Business Insider by Kris Gunnars. Enjoy!
by Did you know some plants like grape, rice and lotus, have more genes than humans? This is contrary to the fundamental thought that humans, being the “most” evolved, should be biologically more complex and therefore possess more genes. How can this be you ask? The current hypothesis is that we come equipped with a significant amount of genetic material from the organisms growing inside our gut. These various bacteria, fungi, parasites and viruses provide signaling for the inner workings of our entire body. They support immune function, moderate inflammatory responses, generate vitamins that we are not capable of making, produce hormones from some of the foods we eat, help us to absorb minerals, and regulate the production of neurotransmitters. Most importantly, they allow our immune system to remain competitive with the rate of evolution of pathogens. Average bacteria have 500,000 generations for each human generation. Humans have only had 350-400,000 generations since the appearance of the earliest hominids in Africa. A team of researchers followed the changes of a genetically similar population of E. Coli for 50,000 generations. At 10,000 generations, a short time from an evolutionary perspective, “…the evolving genomes became increasingly different from their ancestors. Moreover, tremendous diversity accumulated within each population, such that almost every individual had a different genetic fingerprint” (Papadapoulus PNAS 1998)
Some surprises emerged at the 50,000-generation mark. One population had evolved to be able to utilize a completely different energy (food) source. Others changed in size, shape and antibiotic resistance. The successive generations were generally more resilient than the previous generations.
The human microbiome is passed on from generation to generation as an infant passes through the birth canal. The mixing of the mother’s secretions, including feces, provides the inoculation of these beneficial bacteria and fungi. The genetic material that we are carrying inside us today has evolved since the beginning of time and has been passed down through thousands of generations. Most animals on the planet, including many (and possibly all) born through eggs , receive this life-giving inoculation from their mother.
Over the past few years, we have observed a significant increase in autoimmune conditions, exaggerated immune responses, Celiac disease, allergy and asthma. Various factors have been attributed including lack of vitamin D, lack of sufficient parasites, an excessively sterile environment and deficiency of multiple bacteria, some of which are considered pathogenic. As I mention in my previous article, a lack of H. pylori, the bacteria that can cause stomach ulcers, can manifest as asthma. We are seeing startling changes to the human microbiome. Many individuals now require fecal transplants to replenish some of these missing organisms or face chronic illness. This is replacing what should have been passed down through the birth canal. Simply replacing these bacteria with fermented foods or probiotics is not always adequate. There are two reasons for this. First, like the soil, we have only been able to culture and identify only 1% of the organisms growing in the human digestive system. We don’t yet have enough information to re-create such a diverse system. Second, there is a hierarchy to the establishment of bacteria in the gut. E. coli, are like top soil on bedrock. They create a matrix for all the other single-celled creatures to grow and thrive. You can drink a gallon of yogurt daily but if E. Coli is not present, other beneficial species cannot establish themselves. So why not simply replace the E. Coli? Here’s the catch. Most E. Coli strains from other people and animal’s are rejected by our body’s immune system. This is likely why fecal transplants, which can work miracles, but must be obtained from the mother or siblings to avoid complications.
There are hundreds of studies linking cesarean sections (c-sections) and chronic antibiotic use with various autoimmune conditions and other health problems. Here are a few.
- A large study demonstrated a 52% increased risk of asthma in children delivered via cesarean section.
- Another study demonstrated a 2 fold increase in allergic reactions, asthma and sinus issues (J Allergy Clin Immunol 2008;122:274-9.)
- A meta-analysis (a study that looks at all studies on the same subject) revealed 19% increase in type 1 diabetes in children who were delivered via c-section.
- A study demonstrated significant reduction of TNF-alpha inflammatory response in piglets infected by Mycoplasma hyopneumoniae if they were inoculated with commensal bacteria. ***The fact that bacteria moderate inflammatory responses during infection could easily explain the increased incidence of severe allergic reactions.
- Another study demonstrated a significantly increased incidence of Celiac disease in children born via C-section
- Here is a wonderful article summarizing many of this information http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3110651/#R47
- Here is a book that goes into detail about some of these findings and their implications: An Epidemic of Absence – New Ways of Understanding Allergies and Autoimmune Diseases by Moises Velasquez-Manoff
These facts have sparked interest in the scientific and medical communities regarding the practice of cesarean section and antibiotic use. Less well recognized is the detrimental influence of seemingly harmless chemicals upon the microbiomes of various species. In 1974 the miracle herbicide, glyphosate or Roundup ™ was introduced to different agricultural markets in Malaysia, the U.K. and the U.S. Back then, techniques for evaluating the safety of chemicals was primarily based on two aspects. First, was the chemical’s ability to create disease. Second, the dose of the chemical that caused death in 50% of the recipients. (the LD50). Until recently, all studies on glyphosate suggested that most animals could literally drink the stuff without ill effects. However, as our knowledge and research techniques have evolved, we are discovering that we may have made committed irrevocable and possibly unprecedented mistakes in introducing this chemical into our environment.
A study performed on the bacteria populations in the digestive systems of poultry demonstrated that glyphosate caused significant reductions in the populations of various species of beneficial bacteria including Enterococcus faecium, Bacillus badius, Bifidobacterium adolescentis and Lactobacillus spp. (As I referenced above, we now know that beneficial bacteria are passed from the mother hen to her offspring and are inside the developing embryo within the egg). The reduction of these beneficial bacteria allowed overgrowth of bacteria that cause disease in humans like typhoid and botulism along with various other strains of salmonella.
As these pathogens have become more and more prevalent, we have had to use more and more antibiotics to protect ourselves from foods that have been part of the human diet for generations. Of course, the increased antibiotic use has further reduced the populations of the bacteria that prevented the pathogens to begin with. As time passes the pathogens develop more and more resistance to the antibiotics. We’ve replaced a system that worked for thousands of years with a scenario where we must innovate or die. I predict that in five to ten years we will come full circle and use bacteria and fungi as a replacement for antibiotics and to replenish what has been lost.
All of the beneficial bacteria mentioned in the study above are the same ones that exist in the human digestive system. As I have discussed in previous articles, the bacteria residing in our digestive system are reflective of the bacteria growing in the soil. Similar species of Enterobacter, Pseudomonas, Bacillus and Enterococcus are found both in the soil and in the human GI tract.
The world’s grasslands contain within them the highest level of microbial biodiversity of any other soil or ecosystem on the planet. Over millions of years this biodiversity created the dark, deep rich soil that made the Midwest of the United States one of richest resources for food production on the planet. The introduction of glyphosate allowed humanity to produce more food than has ever been possible. However, it is possible that it has already altered our evolutionary path. Dr. Don Huber, Professor Emeritus of Plant Pathology, Purdue University has studied various aspects of soil microbiology and plant pathology for decades. Here is the perspective he offered regarding glyphosate in an interview a few years ago.
“All it does is make it possible for that plant to survive and to accumulate more glyphosate. We still change the soil ecology, microbial ecology, and… our intestinal microbiology.”
Daily discoveries demonstrate that human health is inextricably linked with the health of the tiniest aspects our environment. Through innovation we have overcome many of Nature’s obstacles to create abundance and, for now, have become one of the most successful species on the planet. Through our knowledge we are finding new crossroads where it is obvious our actions are interfering with our own ability to adapt and evolve. It is becoming imperative that we use this knowledge to restore balance to correct the mistakes we have made. Otherwise, we will back ourselves into a corner where innovation is no longer about advancement but obligatory for our own survival.
by With the best of intentions are we slowly rendering our population incapable of developing natural, adaptive immunity? In his upcoming book, Doc, Terry Grossman M.D. gives a powerful example of this as he discusses the pros and cons of vaccines. I would like to expand on the subject.
In 2005, a study by W Katherine Yih et al, was published demonstrating that from 1998-2003 “As varicella vaccine coverage in children increased, the incidence of varicella (chickenpox) decreased [by 79%] and the occurrence of herpes zoster (shingles) increased [by 90%]”. These figures are beyond statistically significant. Similar trends were observed in several areas where the varicella vaccine was initially introduced. The explanation for the unexpected emergence of shingles was this. In any given population, there would have been an ongoing percentage of people with active varicella infection. Chronic, low-grade exposure to the virus throughout the population ensures that it remains on the immune system’s “radar screen” and is therefore kept at bay by our own adaptive immunity. Vaccinations work in a similar fashion. Another study done by Bryson et. Al. predicted that “a substantial increase in herpes zoster cases over the first 30–50 years after the initiation of mass vaccination, peaking about 20 years after the start of mass vaccination at an incidence of 51 percent over the pre-vaccination level and eventually falling below the initial incidence”. doi: 10.1016/S0264-410X(02)00180-9 Another study conducted in Germany also concluded there was sufficient evidence to suggest that varicella vaccinations lead to higher incidents of herpes zoster in the older population.
To be objective, before 2003, herpes zoster was not identified as a nationally notifiable disease, and no states in the US required reporting of cases. The study mentioned above seems to have accounted for record discrepancies within the chosen test site. However, a study came out in 2008 doi: 10.1086/522162 demonstrating that some areas where the varicella vaccine was introduced saw minimal change in reporting of herpes zoster cases. There is one claim in this study that I take major issue with. They state “Evidence from population-based studies suggests that rates of HZ [herpes zoster] were increasing in the United States before the introduction of the varicella vaccination program.” Another study states that the incidence of herpes zoster has been increasing since 1945. In both of these studies, several crucial data points were not accounted for. First, there was no oversight or requirement in reporting of herpes zoster events before the introduction of the vaccine in 1995. Second, access to health care has increased between 1945 and the present. Reports of incidents would not have been consistent through any subsection of the general population. I’m not saying they don’t have some valid points but in a scientific paper, these are presumptive and irresponsible statements. Their conclusion should have been that the data is inconsistent and not available.
There are always unknowns. However, the current research suggests that the introduction of the varicella vaccine saved an average of 90 lives per year and created an anthropogenic chasm in an entire system, between virus and human, that had evolved over the millennia to reach a steady state. Trends like this have the potential to remove human beings from the interconnected web of Evolution and Natural Selection. In this way, technology loses its place as a luxury and instead becomes a necessity of human survival.
by Overconsumption of any sugar has deleterious effects on our health. However, of the primary types of sugars that our cells can utilize; glucose (common in root vegetables and grains), fructose (common in fruit, honey, agave and corn) and galactose (common in legumes and milk) I propose that fructose has the most detrimental effects on human health. Unlike glucose, which is metabolized by most cells as an energy source, fructose is mainly metabolized by liver cells. As I mentioned in my last post, a study appeared way back in 1988 in the Journal of Diabetes Research and Clinical Practice that showed fructose has a reaction constant 7.5 times higher than glucose as well as a much higher calculated biohazard rating. Supporting research has increased exponentially since then.
In small amounts AND in the presence of adequate antioxidants, the liver has no problem metabolizing fructose. In fact, it converts it into glycogen which is the primary fuel for anaerobic muscles (the ones that get really big when you lift weights). Any fructose left after the muscles have had their fill of glycogen is converted into triglycerides. These “feed” fat cells for later use. Depending on which study you read, this occurs if more than 5-7 grams of fructose is consumed in one sitting. In addition to being converted into triglycerides, the excess fructose initiates a damaging, inflammatory response in the liver along with producing elevated levels of free radicals known as reactive oxygen species (ROS).
Here is a brief summary of the amounts of sugar contained in one cup of various fruits and beverages: Please note that I couldn’t find a breakdown of the glucose to fructose ratio. Source: http://nutritiondata.self.com/
- Coke (26g sugar) – almost all fructose
- Bananas (28g sugar)
- Apples (13g sugar)
- Apple juice (24g sugar) – 15 grams of fructose
- Grapes (23g sugar)
- Apricots (14g sugar)
- Cherries (15g sugar)
- Grapefruit (17g sugar)
- Cantaloupe (14g sugar)
- Pears (16g sugar)
- Plums (16g sugar)
- Blueberries (15g sugar)
- Blackberries (7g sugar)
- Raspberries (5g sugar)
- Peaches (13g sugar)
At first, the inflammation and free radical activity initiated in the liver from fructose results in fat accumulation inside the cells and mildly reduced function. If it continues along this path for any amount of time, a condition called non-alcoholic fatty liver disease, NAFLD, develops. Scores of studies demonstrate that along with obesity, NAFLD incidence has been steadily rising in Westernized, developed countries and in counties that are becoming developed. A study showed a 10-year doubling of NAFLD in one Chinese Population and demonstrated that a similar trend was seen in both Korea and Japan.
Note: I thought it would be interesting to compare fructose consumption and NAFLD incidence in various countries. I spent several hours and had a research assistant spend several more hours trying to find information on fructose sales or consumption in various countries. The information is very difficult and seemingly expensive to obtain. If anyone has access to this type of information, please contact me or enjoy the dissertation subject.
I would like to point out that many of these studies are performed by checking serum levels of the liver enzymes ALT and AST. The pathological changes occur way before these enzymes levels begin to rise. According to Dr. Michael Cave, a professor of hepatology, gastroenterology and nutrition at the Univerisity of Louisville, ALT and AST parameters should be much lower because these enzymes only begin to increase long after the inflammation and fat accumulation starts. To be objective, Dr Cave also presents a strong case for an increase in fatty liver disease as a result of chronic exposures to several persistent organic pollutants and xenobiotics. Several studies show that exposing liver cells to fructose, then adding a xenobiotic, results in accelerated inflammation and disease. It is possible that the rise of fatty liver disease has been a combination of increased fructose intake and exposure to these various environmental pollutants that are now ubiquitous in our environment.
Depending on which study you read, NAFLD is seen in 10-24% of America’s general population and 57-74% of obese individuals. According to the Mayo Clinic’s website, they describe fatty liver disease as “common and for most people causes no signs, symptoms or complications”. However, long before any physical symptoms present, the liver’s various functions diminish. If this continues permanent liver damage occurs along with the cumulative toxicity effects of secondary dysfunction. In addition, any persistent organic compounds that aren’t removed from the blood by the liver accumulate in fat tissue.
Here is a brief summary of the main functions of the liver:
- Eliminating endogenous toxins like testosterone and estrogen
- Eliminating exogenous toxins like gasoline vapors, prescription medications, pesticides, artificial fragrances, hormones from birth control usage that are now in the water supply and BPA from the PVC pipes that carry our water.
- Generating antioxidants like glutathione which not only carry out Phase 2 detoxification in the liver but neutralize pollutants in the lungs and assist with the recycling of neurotransmitters in the nervous system
- Metabolizing fat along with various types of cholesterol
- Generating proteins and enzymes for physiological functions all over the body
It makes me cringe to think what is happening to the livers of those poor souls who become motivated to lose a few extra pounds. They go running five miles per day, lift weights then drink a bunch of carrot juice or eat a banana because they’ve been misinformed into thinking it’s healthy. Not only are they putting an extra burden on their liver to metabolize the fat that is being burned, they also have to detoxify the various persistent organic compounds that are released from that fat. For the final assault they add massive doses of fructose. It would be really interesting to check the liver enzyme levels on NBC’s “The Biggest Loser” contestants before and during the competition. If I were them, I would do things to support the poor liver like eating more protein and vegetables, getting rid of the fruit and adding supplements like phosphatidylcholine, folic acid, B6, B12, alpha lipoic acid and N-acetyl cystiene.
Clearly, we evolved with the ability to eat fruit. For the next post in this series, I will discuss this seeming idiosyncrasy along with how the rise of fructose consumption is causing us to devolve.
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