The Gut, Nutrition and Cancer Connection

Gut, Nutrition, Cancer

Does nutrition play any role in cancer prevention?

Does nutrition play any role in cancer causation?

Can nutrition support other cancer treatments?

Can nutrition play a role as a primary cancer treatment?

These are four excellent questions that patients routinely ask. I will use these questions to structure this series on nutrition, the gut, and cancer. Though this series will primarily focus on cancer, the general themes are applicable across the spectrum. From diabetes to autoimmune disease to hormone imbalance, the nutrition-gut connection is applicable across the dis-aise spectrum. I may even highlight some of the non-cancer examples in future posts. I believe that the nutrition-gut relationship will play a significant role in the future of cancer treatment and many other diseases, for that matter.

The conventional medicine stance on these questions is quite clear; there is no connection between diet, what you put in your mouth, the lack of nutrition, the quality of calories, any aspect of cancer prevention or causation, and absolutely not in cancer treatment. Hey, it is just about the U.S. dietary pyramid, right. What has the dietary pyramid brought, other than obesity, diabetes, autoimmune disease, cardiovascular disease, and cancer; don’t forget the #1 risk group in the past COVID19 pandemic was obese individuals. Thank you, pyramid.

Take sugar, for example. The simple sugar, glucose, is an everyday staple in chemotherapy clinics around the U.S and the world. In contrast to the supplements of Holistic, Integrative medicine that include vitamin D, vitamin A, Iodine, and the like; donuts, muffins, candy bars, and other sugar-high foods are the conventional medicine supplements in chemotherapy treatment centers. You see, there is no connection between sugar, glucose, and cancer while on chemotherapy. Yet, glucose is used to diagnose hyper-metabolic cancer activity in the body with Positron Emission Technology imaging because cancer readily takes up glucose to fuel its rapid growth. You may also know this as the PET scan in the often utilized PET/CT scans to diagnose and stage cancer. Isn’t that paradoxical? It is quite impressive that glucose knows it is only to play a role in cancer with PET/CT imaging, but not during chemotherapy treatment.

There is an old idiom, “junk in equals junk out.” The actual author to credit for this phrase is unknown. This well-spoken phrase has passed into the realm of an old wife’s tale, which has become a common means to marginalize and discredit a longstanding, time-tested behavior. This idiom is nothing to laugh at because my experience is that ‘old wives’ and mothers know best when it comes to the health of their families. Never discount the intuition of ‘old wives’ and mothers. Yes, even over that of the physician, which I have learned over the years of clinical practice.

Conventional medicine claims there is no connection between what is put in the mouth and cancer prevention, causation, or treatment—junk in does not equal junk out. I don’t recall that being the case in my infant children. It was clear that their outs were clearly connected to their ins. Ah, memories. How can this connection not be seen by the medical establishment? Likely, it is the result of ignorance. I am not using ignorance as a derogatory term here; it simply means lack of knowledge or information. Whether ignorance is intentional or not is an entirely different issue. Only one hour of what seemed to be thousands upon thousands of lecture hours during my medical school had anything to do with nutrition. That was intentional and unintentional ignorance! Intentional by the professors and unintentional by the students. You can’t even say these lectures were about nutrition. It was more about dis-aise: vitamin D deficiency causes rickets, and vitamin C deficiency causes scurvy. That was it! It is clear that nutrition is seen to have no value in medical education beyond a few diseases. In medical residency, it was worse. The one hour shrunk to zero hours. I guess if you are not going to go big, you go home. In the topic of nutrition in medical school and residency, the educators didn’t go big; they intentionally went home. The result was unintentional student ignorance on the topic of nutrition.

The nutrition, gut, and cancer connection is a little more than just the simple ins and outs. This amazing connection is an intimate connection with the body’s metabolism, immune system and is paramount to a love language with the genetic code—DNA. There is no function within the body untouched by nutrition or lack thereof. For this series, but not limited to this list, the connection involves:

• Nutrigenomics
• Epigenetics
• Dysbiosis
• Hormone imbalance
• Inflammation
• Immune system
• Cancer treatment

I will highlight and discuss each point to draw together the Nutrition-Gut-Cancer connection. The first point to connect here is Nutrigenomics.

Have you ever wondered about how a good diet or a bad diet could affect your body? Or, if you are a skeptic, diet can even affect your body.

I’m not just talking about how nutrition can play a role in how you feel or how the number of calories in and the number of calories out can affect your waist size. I’m talking about how food can affect the literal makeup and function of your body.

A recent study, “Plant miRNAs found in human circulating system provide evidences of cross kingdom RNAi,” published in the journal Genomics,^[1] offers a perspective that may be surprising…and may change your thinking the next time you’re considering eating a baker’s dozen of donuts or heading to the farmer’s market for a head of broccoli.

Basically, plant microRNAs (miRNA) have been found in the blood of humans. This finding is the cause of what the authors call “cross-kingdom RNA interference.” Now, the appropriate question here is what the origin of this plant miRNA is?

For this to sink in, you may want to know exactly what miRNA is. MicroRNA is just one of the many different (piRNA, siRNA, priRNA, lncRNA…) non-coding RNA’s available to affect function. MicroRNAs constitute a significant family of small, non-coding RNAs that are 20-24 nucleotide long single strands of RNA that bind to messenger RNA transcripts to inhibit their translation into proteins and play a significant role in post-transcription gene expression regulation ^[2]. And I thought that food was just calories. Studies have shown that diet is a source of miRNA to the body through dietary intake, gut absorption, and then into the systemic circulation.

Why is this “cross-kingdom RNA interference” important? Ultimately, it answers the question: How can a good diet or a bad diet affect you and your body for health or dis-aise?

How can it affect your body? MicroRNAs can affect your body in BIG WAYS. These miRNAs can actually influence your very genetic expression! Yes, you did read that right. These miRNA can change your very own genetic expression. This dietary altered genetic expression can be good in the case of broccoli, or this can not be good in the case of donuts—more on the specifics of how below.

Our diet is more than just nutrition, calories in/out, and macronutrients. The fact that we think we know everything there is to know about nutrition, metabolism, and the body is laughable on its face; worse, it is dangerously arrogant. A human diet is also a form of communication, a language if you will, and these “languages” affect genetic expression, and the effects ripple throughout the body. These genetic expressions are not limited to the short-term effects of one meal, one week, one decade, or even one body, but can ripple through generations as well, through what is called transgenerational inheritance ^[3]. It is estimated that somatic changes in the DNA code can take thousands of years. In reality, a change in genetic expression can be the result of one meal.

Here are few examples of how nutrition affects genetic expression. Plant miRNA from honeysuckle can inhibit the replication of influenza A. How about something more relevant to cancer? Plant miRNA 159 is shown to target the Transcription Factor 7 (TCF7) gene and inversely correlate to breast cancer incidence and progression. Let me make this more clear; plant miRNA159 can change genetic expression to decrease the growth of breast cancer. Did I get your attention? Plant-based miRNAs have been shown to play roles in the initiation and inhibition of cancer ^[4]. They even have names. MicroRNAs that play a role in tumor initiation and growth are called oncomirs ^[5]. Without a doubt, plant-based miRNAs absolutely can play a role in cancer prevention and treatment.

MicroRNA 159 sounds fancy, right? Are you curious where miRNA 159 comes from? It is not the latest wonder drug that explodes on the national news with great fanfare, only to disappear into oblivion without a trace.

Take a guess…

You won’t find it in a wrapper, a box, or a package.

You can find it at any grocery store.

It is a vegetable.

It is green.

It is of the cruciferous family.

It is…broccoli. Seriously. The miRNA 159 that targets the TCF7 to decrease breast cancer growth comes from broccoli.

Dietary sourced plant miRNAs in human blood have been proven in multiple studies ^{[6] [7]}. Using diet and nutrition to target human gene expression is not new. It is known as Nutrigenomics: the study of nutrition effects on genomic (DNA) expression. It is the communication of diet with your genome or DNA to change genetic expression.

But, there are so many more questions. Like, what is the best type of a plant-based diet? What about food prep? There are so many advocates for this or that food program. But, without an emphasis on gimmicks, what does the science say?

Another study published in 2016, “Circulating plant miRNAs can regulate human gene expression in vitro” answers that question quite clearly:

“…raw or shortly cooked broccoli provides the best source of microRNAs, and potentially strongest health benefits. Interestingly, long exposure to hot water, steaming and blending degrade microRNAs’ integrity, reducing the potential benefits.” ^[8]

That is direct scientific evidence that supports the Raw Food Vegan nutrition program that Dr. Lodi started in 2004. Dr. Lodi advocated the Raw Food Vegan diet long before the raw and vegan diets hit mainstream. Now, that is a pioneer. And what vegetables did this study assess? That would be the Brassica oleracea vegetables. You will better know Brassica oleracea by the more familiar names of broccoli, cabbage, kale, cauliflower, collard greens, and my personal favorite—Brussels sprouts. Mmmmmm! Of note, currently, 64 miRNA are attributed to this class of vegetables. This study’s take-home point is that the more raw the vegetable, the higher the miRNA, which increases the health benefit.

A plant-based diet plays a much more significant role than just delivering plant-based miRNAs; I propose that they can affect human miRNAs expression and activity ^[9]. From the likes of miRNA-17-92 cluster to let-7 family, mir-15a and mir-16-1, components in a plant-based diet affect human miRNA expression and activity. The implications in the initiation, prevention, and treatment of cancer are significant ^[10]. More, plant-based miRNA influences the gut microbiome ^{6 [11] [12]}. A 2015 study, “A novel chemopreventive strategy based on therapeutic microRNAs produced in plants”, showed that plant miRNA alone could reduce tumor burden, though the reduction compared to the control group in this study failed to reach statistical significance ^[13]. However, the trends seen in research supports and are consistent with the effect seen in this study.

See a consistent theme here? It is the nutrition—gut—dis-aise connection. However, this triad is missing one linchpin—inflammation. The nutrition—gut—inflammation—dis-aise connection is called metabolic endotoxemia. I will discuss this topic in the next couple of blog posts because it is at the heart of the relationship of nutrition and health or dis-aise potential.

How can a diet that is good or bad affect your body? Well, it depends on what you are eating! Junk in does, in fact, equal junk out. Don’t be so surprised to find that when you fuel the body with nutrition, the body responds with an amazing functional response. Try putting diesel fuel in a non-diesel fuel car. In contrast, premium, clean fuel provides clean, long life to your car. Hmmm. But, I am sure there is no connection between fuel and car performance.

We invest in what we value. God, family, work, friendships, sports are common arenas of investments in our current day. Nutrition is about investing as well. Take athletes, for example. An athlete invests significant time and effort into their performance. They don’t just wake up one morning and think, I am going to run a marathon. I guess you could, but I wouldn’t suggest it as that is a disaster, on multiple levels, waiting to happen. Take James Lawrence, the Iron Cowboy, for example. He is the Iron Man king. James Lawrence has pushed the human body beyond the limits of imagination. But, he has invested significant time and effort towards this effort. For the non-athlete, how about a test. Try taking your final exam without an investment of study preparation. What outcome, what grade, should one expect? Investment equals opportunity. Investment doesn’t guarantee a positive outcome, but it sets the foundation.

Whether you are eating well or eating poorly, your diet is certainly in communication with your DNA, and as you heard, it is possible to change the very expression of your DNA by what you eat. According to the research presented here, the ability to block breast cancer growth and progression or even to inhibit influenza A were combated by eating certain foods simply found in nature like broccoli or honeysuckle. No doctor visit, no prescription, or copay required; just good old food—real food! Maybe the old wives knew something after all.

Your diet can change your gut microbiome, your DNA, and your very genetic expression. That is the power of food. Nutrigenomics may sound cutting edge, but intuitively you already know how powerful food can be. In the end, you are what you eat. Who do you want to be?

^[1] Liu YC, Chen WL, Kung WH, Huang HD. Plant miRNAs found in human circulating system provide evidences of cross kingdom RNAi. BMC Genomics. Mar 2017;18(Suppl 2):112. doi: 10.1186/s12864-017-3502-3.

^[2] Jansson M.D., Lund A.H. MicroRNA and cancer. Mol. Oncol. 2012;6:590–610. doi: 10.1016/j.molonc.2012.09.006.

^[3] Xavier MJ, Roman SD, Aitken RJ, Nixon B. Transgenerational inheritance: how impacts to the epigenetic and genetic information of parents affect offspring health. Hum Reprod Update. Sep 2019;25(5):518-540. doi: 10.1093/humupd/dmz017.

^[4] Shukla S., Meeran S.M., Katiyar S.K. Epigenetic regulation by selected dietary phytochemicals in cancer chemoprevention. Cancer Lett. 2014;355:9–17. doi: 10.1016/j.canlet.2014.09.017.

^[5] Cho WC. OncomiRs: the discovery and progress of microRNAs in cancers. Mol Cancer. Sep 2007;6:60. doi: 10.1186/1476-4598-6-60

^[6] Zhao Y, Cong L, Lukiw WJ. Plant and Animal microRNAs (miRNAs) and Their Potential for Inter-kingdom Communication. Cell Mol Neurobiol. Jan 2018;38(1):133-140. doi: 10.1007/s10571-017-0547-4.

^[7] Lin Zhang, Ting Chen, Yulong Yin, Chen-Yu Zhang, Yong-Liang Zhang, Dietary microRNA—A Novel Functional Component of Food, Advances in Nutrition. Jul 2019; 10(4):711–721, https://doi.org/10.1093/advances/nmy127

^[8] Pastrello C, Tsay M, McQuaid R. et al. Circulating plant miRNAs can regulate human gene expression in vitro. Sci Rep. 2016;6,32773. https://doi.org/10.1038/srep32773

^[9] Ross SA, Davis CD. The emerging role of microRNAs and nutrition in modulating health and disease. Annu Rev Nutr. 2014;34:305-36. doi: 10.1146/annurev-nutr-071813-105729.

^[10] Garzon R, Fabbri M, Cimmino A, Calin GA, Croce CM. MicroRNA expression and function in cancer. Trends Mol Med. Dec 2006;12(12):580-7. doi: 10.1016/j.molmed.2006.10.006.

^[11] Díez-Sainz E, Lorente-Cebrián S, Aranaz P, Riezu-Boj JI, Martínez JA, Milagro FI. Potential Mechanisms Linking Food-Derived MicroRNAs, Gut Microbiota and Intestinal Barrier Functions in the Context of Nutrition and Human Health. Front Nutr. Mar 2021;8:586564. doi: 10.3389/fnut.2021.586564.

^[12] Yun Teng, Yi Ren, Mohammed Sayed, Xin Hu, Chao Lei, Anil Kumar, Elizabeth Hutchins, Jingyao Mu, Zhongbin Deng, Chao Luo, Kumaran Sundaram, Mukesh K. Sriwastva, Lifeng Zhang, Michael Hsieh, Rebecca Reiman, Bodduluri Haribabu, Jun Yan, Venkatakrishna Rao Jala, Donald M. Miller, Kendall Van Keuren-Jensen, Michael L. Merchant, Craig J. McClain, Juw Won Park, Nejat K. Egilmez, and Huang-Ge Zhang. Plant-Derived Exosomal MicroRNAs Shape the Gut Microbiota. Cell Host & Microbe. Nov 2018;24(5):637-652.

^[13] Mlotshwa S, Pruss GJ, MacArthur JL, Endres MW, Davis C, Hofseth LJ, Pena MM, Vance V. A novel chemopreventive strategy based on therapeutic microRNAs produced in plants. Cell Res. 2015;25(4):521–4.