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Don't let them eat cake

About the author: 
Bryan Hubbard

New research suggests that a diet that drastically restricts carbs could be an effective way to reverse cancer

When it comes to cancer and its causes and treatment, two worlds seem to exist. The first world is the conventional one of chemotherapy and radiotherapy, where cakes and sweets are offered as an energy boost at the end of an arduous treatment—often to prevent life-threatening weakness and weight loss, a condition called cachexia, after chemotherapy.

The second world has noticed a close connection between the disease and the sugar we get from carbohydrates, including the cakes dished out at cancer centres, as well as from starchy foods like bread, pasta and potatoes. This connection was first proposed more than 150 years ago, and it gained traction when scientist Otto Warburg put forward his hypothesis in 1924 that sugar feeds cancer cells.

Although oncologists recognize the 'Warburg effect' as a hallmark of cancer cells, the standard view maintains that all cells need sugar in order to survive, and that a cancer patient doesn't need to follow a low-sugar diet as that could damage the non-cancerous cells. This is borne out by the advice cancer patients are given: the UK's MacMillan Cancer Support provides recipes for sweets like amaretti-stuffed peaches as a pick-me-up treat, while leaflets for cancer patients recommend upping their cake intake to offset weight loss during chemotherapy. One chirpingly states: "Cake is a good thing to eat...it's full of calories too—something you need to have quite a bit of when you are on chemotherapy to try and stop you losing too much weight. Chocolate puddings with sauce can be bought from most supermarkets and are also a great treat." There's even a Facebook page called Cakes Against Cancer with more than 52,000 followers.

Despite the tacit acceptance of Warburg and his theory, it hasn't changed the way Western medicine treats cancer, and this is partly because its compass is set on a drug solution for every disease. Acceptance has also been stalled by the discovery that Warburg wasn't entirely right: different sugars seem to feed various cancers, while others don't, and the whole process may have something to do with inflammation, rather than the way cells respire, or 'breathe', as Warburg suggested.

Now, in breakthrough research, scientists from Trinity College Dublin have squared the circle between the Warburg hypothesis and others who've come to slightly different conclusions. The Dublin research team has discovered that some cells, and crucially the ones in our immune system that fight cancer, are activated when they are starved of sugar.

This suggests that a diet that drastically restricts carbohydrates—such as a ketogenic diet or the Atkins diet—is an effective way to reverse cancer. Now they just have to convince the doctors.

Sugar, sugar

It's previously been established that when many types of immune cells are starved of glucose (blood sugar), they become dysfunctional. But in their new study, the Trinity College researchers discovered that the reverse is true for the immune cells that monitor our body for signs of danger. When these cells, known as dendritic cells, are deprived of glucose, they activate special disease-fighting cells called T-lymphocytes.1

"We have discovered that dendritic cells are actually better at stimulating immune responses when starved of glucose, which is not the case for any of the other immune cells that have been analyzed", said lead researcher David Finlay.

"The discovery that T-cells and dendritic cells compete with each other for glucose offers a new and exciting insight into how glucose can regulate dendritic cell function."

Warburg was seeing another mechanism at play with glucose, and one that was directly affecting the cancer cells. Essentially, cancer cells don't respire the way that healthy cells do; instead, they ferment glucose for energy.

Warburg continued working on the theory—even winning the Nobel Prize in Medicine in 1931—and coming up with more evidence. In a speech to fellow Nobel laureates in 1966, he concluded, "The prime cause of cancer is the replacement of the respiration of oxygen in normal body cells by a fermentation of sugar."

Yes, but . . .

But not all scientists agree with Warburg, at least not entirely. In 2009, researchers at Thomas Jefferson University proposed that the 'Warburg effect' actually occurs in connective tissue cells, and not in the cancer cells themselves. Essentially, cancer isn't a process of glucose fermentation but of energy imbalance. The cancer is able to grow and spread happens because cancer cells have defective mitochondria, which help convert energy in cells, a phenomenon they called the 'Reverse Warburg effect'.2

Other researchers have claimed that it's fructose, the sugar from fruit, that is the real culprit, especially for promoting the growth of breast cancer. A research team from the University of Texas MD Anderson Cancer Center discovered in experiments on laboratory mice that fructose was affecting a metabolic regulator, known as 12-LOX (lipoxygenase), that was helping breast and lung cancer cells to spread.

Half the mice fed extra sugar developed breast tumours, compared to 30 percent of control mice, and there was a direct association between the amount of sugar consumed and the size and spread of the tumours. Although all types of sugars fed to the mice accelerated tumour growth, fructose had the most damaging effect and was worse than glucose.3

But the researchers don't claim that eating fruit helps cancer spread. People get most of their fructose from processed foods and drinks, which are sweetened by high fructose corn syrup (HFCS). Processed foods and drinks have caused annual consumption of high fructose corn syrup in the US to rise from around half a pound (0.22 kg)
in 1970 to 62 lbs (28 kg)
by 1997.

Like breast cancer, other cancers also seem to need sugar more than others. For example, a form of lung cancer known as squamous cell carcinoma (SqCC) is especially reliant on sucrose for its growth. SqCC cells contain exceptionally high levels of a protein called glucose transporter 1 (GLUT1), which, as the name suggests, carries glucose from the blood into the cell, where it can be used as an energy source. By comparison, another type of lung cancer—adenocarcinoma—produced ten times less GLUT1 than SqCC and was far less reliant on sugar for its growth.4

The general theme that sugar feeds cancer isn't new. In 1885, physician Ernst Freund noticed that all of the 70 cancer patients he was treating were suffering from hyperglycaemia, or high blood sugar. Since then, doctors have confirmed that cancer patients have poor glucose tolerance and insulin sensitivity, a similar profile to diabetic patients.

In 1924, two scientists, Handel and Tadenuma, demonstrated that insulin encouraged cancer cell growth in animal tests—and so, conversely, reducing insulin by cutting down on carbohydrates in our diet could also slow or stop tumour growth.

Then along came Warburg, whose insights won him the Nobel Prize—but surprisingly little acceptance by the medical establishment. Every year, new research comes along that fine-tunes the theory, but regardless of the details, just pass on the cake.

Know your sugars

Our body needs sugar to survive, and gets it from carbohydrates, otherwise known as saccharides, which are sugars or starches. The starches include bread, pasta, beans, potatoes, bran, rice and cereals.

The simple sugars, or monosaccharides, are:

Glucose: This is the most important monosaccharide because it's the one that the body uses for energy. Other dietary sugars and carbohydrates are converted to glucose, which, when released into the blood stream, is known as blood sugar. A rise in blood-sugar levels causes the pancreas to release insulin. The one exception is fructose, which is metabolized in the liver, making it the only sugar that diabetics can tolerate.

Fructose: This is a sugar in fruits and vegetables, and it's added to drinks such as sodas and fruit-flavoured drinks. It's also found in high fructose corn syrup (HFCS), which is added to many processed foods. It's metabolized in the liver, and so insulin isn't released to break it down, but it acts more like a fat than a sugar, causing other health problems.

Sucrose: This is also known as table sugar, and it's found in sugar cane and sugar beets. Fruits and vegetables also contain sucrose.

Lactose: This is a sugar found in milk.



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References

References
1 Nature Communications, 2017; 8: 15620
2 Cell Cycle, 2009; 8: 3984-4001
3 Cancer Research, 2017; doi: 10.1158/0008-5472.CAN-14-3432
4 Nature Communications, 2017; 8: 15503

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