The topic of Cancer

For the last few weeks I have been indulging in a little side project. This involved reviewing a list of 394 Indian herbals, screening their ethnobotannical uses and cross-referencing them against the body of more recent research that has been done into their pharmacological and clinical properties. 

In the process, a few things became evident to me. I began to see more clearly than before just why and how a plant-based diet reduces the risk of cancer. Conversely, it became rather obvious why cancer has become so very fashionable in our developed nations. From there, it was a short jump to grasping how some of our theories of cancer have gone so wrong; and how these misunderstandings have created a climate of medical fatalism where people think that if they live long enough, cancer is inevitable.

Given the statistics, this kind of fatalism hardly surprising.

In developed nations, cancer is either the number 1 or 2 cause of death, just before or after cardiovascular disease.

In the USA, for example, an estimated 1,735,350 new cases of cancer will be diagnosed in 2018, and 609,640 people will die from the disease (1). In the EU, where updated figures are harder to find, there were in 2012 an estimated 3.5 million new cancer cases and 1.9 million cancer deaths. Globally, Denmark takes pride of place, with a cancer rate about 4 times higher than Yemen; where being alternately bombed and starved by the Saudis, Israelis and Americans is a clearer and more present danger.

Moving from the macro towards the micro, I know hundreds of cancer patients professionally. And when I stopped to think about it, I realised that I knew at least 35 cancer patients personally. In some of the families I have social ties with, almost every member of my vintage (circa 70 and above) has cancer. And they think it’s normal.

But it isn’t. Most of today’s burden of cancer is avoidable. In fact, about 90% of cancer is avoidable. Let me explain.

Years ago when I was studying public health in mid-Victorian England, I and my colleague, the inestimable historian Dr Judith Rowbotham, identified a population who lived as long as we do today but in whom cancer was a rarity. Cancer was diagnosed at levels around 10% of what we see today. That figure of 10% is highly significant, because oncologists will tell you today that about 10% of their patients have strong genetic risk factors. For the other 90% there is no apparent cause, other than the steady, age-related accumulation of genetic errors first proposed by the legendary biologist Bruce Ames.

But Ames is demonstrably wrong. In the mid-Victorians, cancer did NOT increase with age. It spiked in the late 30’s and early 40’s, and then disappeared. Older persons hardly got cancer at all. 

I am pretty certain that this pattern – which is very different from cancer epidemiology today – was because the only people who got cancer in that age were those who had the strong genetic risk factors. Everyone else was protected by the Victorians’ incredibly nutrient-dense and chemo-protective diet until they died, typically of overwhelming infection.

Ames is right when he says that genetic mutations are forming in every cell of your body every day; and that if enough of these accumulate in a single cell, they reach the point where that cell acquires a cancer-enabling genome. If the genetic errors accumulate with time, and the host is unprotected, then the exponential risk of cancer that we see occuring with aging will be the end result. 

But Ames is wrong, wrong and wrong again when he says that this is inevitable. It is nothing but an artifact, and his theories are wrong because they suffer from ahistoricism and gross sampling error. 20^th and 21^st century research animals, including humans, are an artifact. And in the 19^th century, cancer did not increase with age.

Years ago I tussled with Bruce at a conference in Denmark. He was on stage, I was in the audience, and after his set speech I was given the first question. I told him that the age-related incidence of cancer had been very different in the recent and well-documented past, and asked for his comments. He was rudely dismissive. Unlike the great Louis Pasteur, who in old age conceded that Claude Bernard was right and that he, Pasteur, was at least partly wrong, Ames’ mind had closed. Convinced of his rightness, Bruce was no longer open to new and potentially conflicting evidence; and at that point I lost most of my respect for the man. He clearly did not know his history, nor did he care to know it; and he did not understand that our ‘normality’ is both temporary and artificial. It is not normal to subsist on hamburgers, shakes and fries, or on any of today’s processed foods, which have little in common with the foods we consumed in previous millenia.

There are hundreds if not thousands of chemo-protective compounds in plant-based foods. These are loosely categorized as phytonutrients.

If f you eat a diet depleted in these compounds, as we do today, then mutations and cancer cells inevitably accumulate, and clinical cancer does indeed become more likely over time. But if you eat a diet rich in phytonutrients, any cancer cells that form in the body are surrounded by a sea of hostile factors, and die off before they can become clinically evident. Except, of course, in those who have strong genetic risk factors, who typically develop cancer in early middle age. Everyone else, as we see in mid-Victorian England, is protected.

Back to the list of 394 traditional Indian herbals. As I reviewed their ethnobotanical histories, I found more and more plants that had been used, traditionally, to treat cancer. And when I started to examine the more recent science, I found more and more evidence that they contained many compounds that did indeed slow down, kill or transform cancer cells. 

These protective compounds are many and various, and they include peptides, cyclotides (cyclic peptides), and peptide alkaloids; saponins and phytosterols, terpenoids such as carotenoids and xanthophyls, phenylethanoids, glucosinolates including the well known indoles, betalaines, a huge family of phenolics including polyphenols, flavonoids, isoflavonoids, aurones, chalconoids, flavonolignans, lignans, stilbenoids, curcumuninoids, tannins such my favourite phlorotannins; and polysaccharides and other functional fibers. (Note – this is a geek-list, normal people can skip this part).  

Once upon a time our diet contained huge amounts of all of these chemo-protective compounds. But when you look into the average supermarket trolley, you can see that they have almost all disappeared.

In other words, the damping elements have been pulled out of the bio-reactors of our bodies. So we get cancer by the bucket-load. We tip the odds further against us if we smoke, drink high-octane alcoholic beverages, and do not take enough exercise. And then we entrust ourselves to the not-so-tender mercies of our brave oncologists, quite a few of whom have confided in me – after a couple of drinks – that if they got cancer, they would use only palliative therapy.

We know why cancer treatment is harmful, but why is it so ineffective? Because cancer cells tend to be genetically unstable. If you pour a poison onto that roiling mass of genetically different cancer cells, you select, over time, for poison-resistant cells. This is why chemo and radio can be so effective at first, and why they become less effective over time. It is a micro-Darwinnian situation; oncologists create treatment-resistant cancer cells in the same way doctors select for antibiotic-resistant bacteria in hospitals.

Eating a phytonutrient-rich diet is different. Instead of trying to kill the cancer cell(s) with a single bullet, the phyto-diet surrounds the cancer cell on all sides with multiple insults and hurdles; and it is almost impossible for that cell to mutate its way out of so many troubles and thrive to the point where it becomes a clinical problem.

Phytonutrients make life difficult for the cancer cell in many ways. If you’re interested, here are a few of them. (It is another geek-list, so feel free to skip this one too.)

1. Inhibit DNA topoisomerase II. 
2. Inhibit BRAF, WNT/β-catenin and Akt-NF-κB converging in MITF-M, leading to complete abolition of MITF-M.
3. Inhibit cyclin D1 expression
4. Induce the cleavage of caspase-3 and poly (ADP-ribose) polymerase 1 (PARP-1). 
5. Regulate multiple cell signaling pathways including cell proliferation pathway (cyclin D1, c-myc), cell survival pathway (Bcl-2, Bcl-x, cFLIP, XIAP, c-IAP1), caspase activation pathway (caspase-8, 3, 9), tumor suppressor pathway (p53, p21), death receptor pathway (DR4, DR5), mitochondrial pathways, and protein kinase pathway (JNK, Akt, and AMPK).
6. Inhibit p65 and cell invasion by down-regulation of COX-2 and MMP-2 expression
7. Suppress gene expression of EGFR and modulation of Akt/mTOR signaling, and inhibition of cell growth.
8. Attenuate the benzo[a]pyrene-7,8-diol-9,10-epoxide-induced activation of AP-1 and NF-κB and phosphorylation of MEK, MKK4, Akt, and MAPKs.
9. Block the activation of the Fyn kinase signaling pathway
10. Block the ethanol-induced activation of the ErbB2/cSrc/FAK pathway 
11. Modulate the receptor tyrosine kinase/PI3K/Akt signaling pathway
12. Transduce signaling via the aryl hydrocarbon (Ah) receptor, NF-κB/Wnt/Akt/mTOR pathways, impinging on cell cycle arrest, modulating key CYP enzymes, altering angiogenesis, invasion, metastasis and epigenetic behavior of cancer cells.
13. Inhibit the anti-apoptotic protein Bcl-xl 
14. Interfere with EGFR signaling
15. Inhibit hepatocyte growth factor-induced cell proliferation
16. Inhibit mitogen-activated protein kinases (MAPK), cyclin-dependent kinases and growth factor-related cell signaling
17. Activate activator protein 1 and NF-κB, topoisomerase I and matrix metalloproteinases.
18. Modulate 671 Nrf2-dependent and 256 Nrf2-independent genes
19. Inhibit Wnt signaling through the modulation of beta-catenin expression, transcriptional activity and the subsequent expression of Wnt target genes
20. Decrease cell viability with G1-phase arrest and disrupted Wnt/β-catenin signaling
21. Inhibit the abilities of adhesion, migration, and invasion, and significantly decrease the nuclear levels of nuclear factor kappa B (NF-κB) and activator protein-1 (AP-1)
22. Overcome the multidrug resistance caused by the high expression of the plasma membrane drug transporter P-glycoprotein (P-gp)
23. Increase the expression of death receptors DR4 and DR5, cleaving caspase-3, inducing caspase-8 and truncating BID
24. Down-regulate ERK1/2 and MEK phosphorylation while maintaining the expression of JNK and phospho-p38 MAPK
25. Induce apoptosis mediated by the activation of caspase-8, -9, and -3-dependent pathways
26. Induce cleavage and degradation of PARP, accompanied by the caspase-independent down-regulation of Mcl-1, Akt inactivation, and activation of JNK
27. Increase AP-1-luciferase activity

This list is, to be honest, a jumble. It is incomplete, there is some overlap, and I do not fully understand any of the anti-cancer links although I do have a broad understanding of some of them. But what I can see is that if you eat a diet containing a rich diversity of phytonutrients with all of the above properties, and cancer cells that do form in your body, they will have nowhere to go. They will die quickly, silently, and never become a clinical problem. 

This explains the near-immunity of the mid-Victorians to cancer, and our astonishing vulnerability. And it explains why, if you go to the extreme of our shoddy feed chain and progress to a diet of ultra-processed foods, your cancer risk goes up by yet another 10% (3). 

These processed and ultra-processed  foods are defective and dangerous. Their content of phytonutrients is effectively zero. They replace cancer-protective phytonutrients with cancer-promoting chemicals such as AGE’s and ALE’s, and cancer-enabling compounds such as sugar and saturated fat. They make us fat, diabetic and inflamed. And they give us cancer. 

The fact that this diet does not drive cancer incidence up to 100% is a testimony, I think, to the exquisite, evolution-honed balances and counter-balances inside us that give us life. But increasingly, those balances are being overwhelmed.

The multinational food companies are killing us en masse. 

If you want to do something about this, here is a simple 5-step route to better health and less cancer.

Step 1. Stop eating ultra-processed foods.

Step 2. Learn how to cook.

Step 3. Eat more fresh vegetables and fruits. The more variety, the better.

Step 4. Add large amounts of spices, because spices are among the richest sources of phytonutrients. If these taste too strong for your Western taste buds, do as the Indians do; mute the spices with ground nuts, flours and/or yoghurts.

Step 5. Add sprouted grains and pulses to your diet. These are another rich source of phytonutrients. 

How to make sprouted grains and pulses

1. Soak the whole grains (or the peas, beans or lentils) in water
2. Rinse, drain and keep moist inside a jar for 1-5 days until the sprouts appear.  
3. Enjoy! 

References:

1. https://www.cancer.gov/about-cancer/understanding/statistics
2. http://canceratlas.cancer.org/the-burden/cancer-in-europe/
3. Fiolet T, Srour B, Sellem L, Kesse-Guyot E, Allès B, Méjean C, Deschasaux M, Fassier P, Latino-Martel P, Beslay M, Hercberg S, Lavalette C, Monteiro CA, Julia C, Touvier M. Consumption of ultra processed foods and cancer risk: results from NutriNet-Santé prospective cohort. BMJ. 2018 Feb 14;360:k322.