Cholesterol Feeds Breast Cancer Cells

One in eight American women will be diagnosed with breast cancer in their lifetimes. There are a number of compounds in plant foods that may protect against breast cancer by a variety of mechanisms. I’ve talked about the benefits of broccoli, flaxseeds and soy foods, but this recent study out of Germany reported something new. Evidence for reduced breast cancer risk associated with consumption of sunflower and pumpkin seeds. Sunflower and pumpkin seeds were associated with reduced breast cancer risk, which they initially chalked up to the lignans in the seeds, something else I’ve talked about, but their lignan lead didn’t pan out. Maybe it’s the phytosterols found concentrated in seeds.

There is evidence phytosterols may be anticancer nutrients that may play a role in reducing breast cancer risk. I thought phytosterols just lowered cholesterol? What does cancer have to do with cholesterol?

Well, increasing evidence demonstrates the role that cholesterol may play in the development and progression of breast cancer. Cancer feeds on cholesterol. Transformed cells take up LDL, so-called bad cholesterol, and are capable of stimulating the growth of human breast cancer cells in a petri dish. See all these little red dots, that’s fat that the breast cancer cells are gobbling up.

The ability to accumulate fat and cholesterol may enable cancer cells to take advantage of people eating high fat and high cholesterol diets. Increased dietary cholesterol intake may result in increased breast cancer risk, and may at least partially explain the benefit of a low-fat diet on lowering human breast cancer recurrence.

Though data has been mixed, the largest study to date found a 17% increased risk in women who had cholesterol over 240, compared to women whose cholesterol was under 160, though they cannot rule out that there may be something else in cholesterol-raising foods that’s raising breast cancer risk.

Tumors suck up so much cholesterol that LDL has been considered a vehicle for targeting antitumor drugs to cancer cells. Since cancer feeds on cholesterol, maybe we could stuff some chemo into it as like a poison pill. That’s probably why people’s cholesterol levels drop so low after they get cancer—the tumor is eating it up.

In fact, patient survival may be lowest when cholesterol uptake is highest. High LDL receptor content in breast cancer tissue seems to indicate a poor prognosis, suggesting that breast tumors rich in LDL receptors may grow rapidly in the body. We’ve known about this for decades. You can tell this is an old study: back in the 80’s only 1 in 11 American women got it.
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Starving Cancer with Methionine Restriction

In designing an antibiotic, you couldn't create a drug that destroyed DNA, for example, because that's something that both humans and bacteria share in common. It would kill bacteria, all right, but it might kill us, too. Instead, many antibiotics work by attacking bacterial cell walls, which is something bacteria have that we don't.

Antifungals can attack the unique cell walls of fungus. Pesticides can work by attacking the special exoskeleton of insects. But fighting cancer is harder, because cancer cells are our own cells. So fighting cancer comes down to trying to find and exploit differences between cancer cells and normal cells.

Forty years ago, a landmark paper was published showing for the first time that many human cancers have what's called absolute methionine dependency, meaning that if you grow normal cells in a Petri dish without given them the amino acid methionine, then normal cells thrive; but without methionine, cancer cells die. Normal breast cells, for example, grow no matter what, with or without, but leukemia cells—they need that extra added methionine to grow.

What does cancer do with the methionine? Well, tumors generate gaseous sulfur-containing compounds with it – that, interestingly, specially trained dogs can actually detect. There are mole sniffing dogs that can pick out skin cancer. There are breath-sniffing dogs that can pick out people with lung cancer. Pee-sniffing dogs that can diagnose bladder cancer and, yes, you guessed it, fart-sniffing dogs for colorectal cancer. Doctors can now bring their lab to the lab…

Gives a whole new meaning to the term "pet scan."

Anyway, methionine dependency is not just present in cancer cell lines in a Petri dish. Fresh tumors taken from patients show that many cancers appear to have a biochemical defect that makes them dependent on methionine, including some tumors of the colon, breast, ovary, prostate, and skin. Pharmaceutical companies are fighting to be the first to come out with a drug that decreases methionine levels, but since methionine is sourced mainly from food, a better strategy may be to lower methionine levels by lowering methionine intake, eliminating high methionine foods, or both, to help control cancer growth.

Here's the thinking: look, smoking cessation, consumption of diets rich in plants, and other lifestyle measures can prevent the majority of cancers. Unfortunately, people don't do them, and as a result, each year hundreds of thousands of Americans develop metastatic cancer. Chemotherapy cures only a few types of metastatic cancer…Unfortunately, the vast majority of common metastatic cancers, like breast, prostate, colon, and lung, are lethal. We therefore desperately need novel treatment strategies for metastatic cancer, and dietary methionine restriction may be one such strategy.

So, where is methionine found? Particularly in chicken, and fish. Milk, red meat and eggs have less, but if you really want to stick with lower methionine foods, fruits/nuts/veggies/grains and beans are the best. In other words, "In humans, methionine restriction may be achieved using a predominately vegan diet.”

So why isn't every oncologist doing this? "Despite many promising preclinical and clinical studies in recent years, dietary methionine restriction and other dietary approaches to cancer treatment have not yet gained wide clinical application. Most clinicians and investigators are probably unfamiliar with nutritional approaches to cancer. [That's an understatement.] Many others may consider amino acid restriction as an “old idea,” since it has been examined for several decades. However, many good ideas remain latent for decades if not centuries before they prove valuable in the clinic. With the proper development, dietary methionine restriction, either alone or in combination with other treatments, may prove to have a major impact on patients with cancer.”
V. Agrawal, S. E. J. Alpini, E. M. Stone, E. P. Frenkel, A. E. Frankel. Targeting methionine auxotrophy in cancer: discovery & exploration. Expert Opin Biol Ther 2012 12(1):53 - 61.

M. F. McCarty, J. Barroso-Aranda, F. Contreras. The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med. Hypotheses 2009 72(2):125 - 128.

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M. López-Torres, G. Barja. Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible implications for humans. Biochim. Biophys. Acta 2008 1780(11):1337 - 1347.

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Cancer Reversal Through Diet?


Just like with diabetes, the same diet that prevents heart disease, can be used not just to treat it, but to reverse it. Next year is the 20 year anniversary of Dean Ornish’s landmark research showing that—without drugs—a near vegan diet could reverse atherosclerosis, dissolve the plaque, open up the arteries.
Well, if that’s the case, can’t we just eat whatever we want then just go vegan after our first heart attack to dissolve the plaque away? Unfortunately, there’s a little something called sudden cardiac death. Half of those that die of heart disease just drop dead, so our first heart attack may indeed our last, but not in the way we were hoping.
So what’s Ornish up to these days? Well, he’s still reversing heart disease. Nearly three quarters of patients angina-free without drugs or surgery. But now that he’s conquered the number one killer, he’s moved on to trying to reverse killer number 2, ,,, cancer.

PSA levels are typically what’s used to follow the progression of prostate cancer. In the standard diet group they got worse, in the vegan diet group they got better. No surgery, no chemotherapy, no radiation—they just started getting better. Here’s an MR spectrograph showing the drop in cancer activity on the plant-based diet.

To figure out what was going on, they took blood from each group and dripped their blood on prostate cancer cells in a petri dish to see what affect the dietary change had. The blood of the standard diet patients did reduce the cancer cell growth rates by about 10%. Their bodies, their immune systems were doing what they could to beat back the cancer. The blood of people on a vegan diet, though, knocked the cancer growth down 70%. Eating a plant based diet made their bloodstream eight times less hospitable to cancer.

Now this is after a year. Subsequent studies have shown that one can see a significant cancer-fighting effect after just two weeks on a plant-based diet with exercise.
What’s happening, it seems, is that the vegan diet reprogrammed gene expression within the prostate gland itself. Ornish took biopsies before and after the dietary change, and you can see the subtle shift in gene regulation from more red to more green—the green denotes genes that are being downregulated by the lifestyle changes. Before, and after.

Ornish’s two year followup was just published last year. A significant number of the standard diet group were forced to go into surgery for what’s called a radical prostatectomy, which often leads to urinary incontinence and impotence in 60% of men coming out of surgery. , But not a single one of the men on the plant-based diet had to go to surgery.

Ornish D, Scherwitz LW, Billings JH, Brown SE, Gould KL, Merritt TA, Sparler S, Armstrong WT, Ports TA, Kirkeeide RL, Hogeboom C, Brand RJ. Intensive lifestyle changes for reversal of coronary heart disease. JAMA.16;280(23):2001-7, 1998.

Chugh SS, Reinier K, Teodorescu C, Evanado A, Kehr E, Al Samara M, Mariani R, Gunson K, Jui J. Epidemiology of sudden cardiac death: clinical and research implications. Prog Cardiovasc Dis. 51(3):213-28, 2008.

J. Frattaroli, G. Weidner, T. A. Merritt-Worden, S. Frenda, and D. Ornish. Angina pectoris and atherosclerotic risk factors in the multisite cardiac lifestyle intervention program. Am. J. Cardiol., 101(7):911-918, 2008.

Ornish D, Weidner G, Fair WR, Marlin R, Pettengill EB, Raisin CJ, Dunn-Emke S, Crutchfield L, Jacobs FN, Barnard RJ, Aronson WJ, McCormac P, McKnight DJ, Fein JD, Dnistrian AM, Weinstein J, Ngo TH, Mendell NR, Carroll PR. Intensive lifestyle changes may affect the progression of prostate cancer. J Urol., 174(3):1065-9; discussion 1069-70, 2005.

R. J. Barnard, N. Kobayashi, and W. J. Aronson. Effect of diet and exercise intervention on the growth of prostate epithelial cells. Prostate Cancer Prostatic Dis., 11(4):362-366, 2008.

Ornish D, Magbanua MJ, Weidner G, Weinberg V, Kemp C, Green C, Mattie MD, Marlin R, Simko J, Shinohara K, Haqq CM, Carroll PR. Changes in prostate gene expression in men undergoing an intensive nutrition and lifestyle intervention. Proc Natl Acad Sci U S A. 17;105(24):8369-74, 2008.

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Atkins Diet: Trouble Keeping It Up

Remember the Atkins Diet? I wrote a book about it a few years ago.  The Atkins Corporation threatened to sue me, but I kind of won by default, because they declared bankruptcy six months later. You can read the whole book and my rather amusing back-and-forth with Atkins' lawyers at http://atkinsexposed.org/.

Here's an illustrative case report of what can happen when you go on such a diet, reported recently in the Journal of the American Dietetic Association: "Development of symptomatic cardiovascular disease after self-reported adherence to the Atkins diet".

Started out healthy, 51-year-old man; pretty good cholesterol, no chest pain, and a working penis. He was gaining a few pounds, though, so he decided to go on a low-carb diet. One month in, his cholesterol shot through the roof, but hey, he lost five pounds, so, he kept it up. And after two years more on the diet, he lost three pounds, but he also lost the ability to have an erection.  And he started having chest pains. But hey, that's what drugs are for, so he started taking Viagra, one of the wonders of modern medicine, which also came in handy when he landed in the emergency room with crushing chest pain.

He got a cardiac catheterization which found a 99% blockage of one of his coronary arteries supplying blood to his heart. Luckily, they found it in time. He got a drug-eluding stent placed.

He was eventually discharged from the hospital and finally decided, maybe this Atkins thing isn't such a great idea, so he switched to a low-fat diet with greens, whole grains, beans, vegetables, nuts, and even (gasp!) the inclusion of vegetarian entrees. Two months on the new diet, his weight was down, his cholesterol was down, and he stopped taking the Viagra.

Now, a skeptic might suggest that he had clogged arteries before he even started the low-carb diet. But no, he actually got a coronary artery scan right before starting on Atkins and there was no measurable plaque in his coronary arteries. And then just 29 months later, after the initiation of the low-carb diet, 99% blockage. Now they were able to open that surgically with a stent, but it took his changing to a more healthy diet to open up blood flow to other parts of his body.

Barnett TD, Barnard ND, Radak TL. Development of symptomatic cardiovascular disease after self-reported adherence to the Atkins diet. J Am Diet Assoc. 2009 Jul;109(7):1263-5.

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Low Carb Diets and Coronary Blood Flow

People going on low carb diets may not see a rise in their cholesterol levels. How is that possible? Because weight loss by any means can drop your cholesterol. You could go on an all-Twinkie diet and lower your cholesterol if you were unable to eat the dozen daily Twinkies necessary to maintain your weight. That’s why a good cocaine habit could end up lowering your cholesterol. Chemotherapy, can drop your cholesterol like a rock. Tuberculosis can work wonders on your waistline. Anything that drops your weight can drop your cholesterol, but the goal isn’t to fit into a skinnier casket, the reason we care about cardiovascular risk factors like cholesterol is because we care about cardiovascular risk, the health of our arteries.

Well now we have studies that have measured the impact of low carb diets on arteries directly, and a review of all the best studies to date found that low carb diets impair arterial function, as evidenced by a decrease in flow-mediated dilation, meaning low carb diets effectively stiffen people’s arteries, And since that meta-analysis was published a new study found the same thing. A dietary pattern characterized by high protein and fat, but low carbohydrate was associated with poorer peripheral small artery function, again measuring blood flow into people’s limbs. But peripheral circulation is not as important as the circulation in the coronary arteries that feed our heart.

There has only been one study ever done measuring actual blood flow to the heart muscles of people eating low carb diets and this is it. Dr. Richard Fleming, an accomplished nuclear cardiologist, enrolled 26 people into a comprehensive study of the effects of diet on cardiac function using the latest in nuclear imaging technology--so-called SPECT scans, enabling him to actually directly measure the blood flow within the coronary arteries.

He then put them all on a healthy vegetarian diet, and a year later the scans were repeated. By that time, however, 10 of the patients had jumped ship onto the low carb bandwagon. At first I bet he was pissed, but surely soon realized he had an unparalleled research opportunity dropped into his lap. Here he had extensive imaging of 10 people following a low carb diet and 16 following a high carb diet. What would their hearts look like at the end of the year? We can talk about risk factors all we want, but compared to the veg group, did the coronary heart disease of the patients following the Atkins-like diets improve, worsen, or stay the same?

Those sticking to the vegetarian diet showed a reversal of their heart disease as expected. Their partially clogged arteries literally got cleaned out. They had 20% less atherosclerotic plaque in their arteries at the end of the year than at the beginning. What happened to those who abandoned the treatment diet, and switched over to the low carb diet? Their condition significantly worsened. 40 to 50% more artery clogging at the end of the year. Thanks to the kind generosity of Dr. Fleming we see the changes in blood flow for ourselves.

Here are some representative heart scans. The yellow and particularly red represent blood flow through the coronary arteries to the heart muscle. This patient went on a plant-based diet and their arteries opened right up increasing the blood flow. This person, however, started out with good flow, but after a year on a low carb diet, they significantly clogged down their arterial blood flow.

So this is the best science we have, demonstrating the threat of low carb diets, not just measuring risk factors, but actual blood flow in people’s hearts on different diets. Of course the reason we care about cardiac blood flow, is we don’t want to die, and a meta-analysis was recently published that finally went ahead and measured the ultimate end-point, death, and low-carb diets were associated with a significantly higher risk of all-cause mortality, meaning living a significantly shorter lifespan.

H. Noto, A. Goto, T. Tsujimoto, M. Noda. Low-carbohydrate diets and all-cause mortality: A systematic review and meta-analysis of observational studies. PLoS ONE 2013 8(1):e55030.

J. Merino, R. Kones, R. Ferré, N. Plana, J. Girona, G. Aragonés, D. Ibarretxe, M. Heras, L. Masana. Negative effect of a low-carbohydrate, high-protein, high-fat diet on small peripheral artery reactivity in patients with increased cardiovascular risk. Br. J. Nutr. 2013 109(7):1241 - 1247.

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L. Schwingshackl, G. Hoffmann. Low-carbohydrate diets impair flow-mediated dilatation: Evidence from a systematic review and meta-analysis. Br. J. Nutr. 2013 110(5):969 - 970.

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