Starvation Based Chemotherapy: A Novel Approach for Cancer Treatment [pdf]
omjournal.org
omjournal.org
Abstract
Cancer patients undergoing chemotherapy treatment are advised to increase food intake to overcome the therapy-induced side effects, and weight loss. Dietary restriction is known to slow down the aging process and hence reduce age-related diseases such as cancer. Fasting or short-term starvation is more effective than dietary restriction to prevent cancer growth since starved cells switch off signals for growth and reproduction and enter a protective mode, while cancer cells, being mutated, are not sensitized by any external growth signals and are not protected against any stress. This phenomenon is known as differential stress resistance (DSR). Nutrient signaling pathways involving growth hormone/insulin-like growth factor-1 axis and its downstream effectors, play a key role in DSR in response to starvation controlling the other cell maintenance systems, such as autophagy and apoptosis, that are related to the tumorigenesis. Yeast cells lacking these effectors are better protected against oxidative stress compared to normal cells. In the same way, starvation protects many cell lines and mice against high-dose chemotherapeutic drugs. According to a series of studies, fasting results in overall reduction in chemotherapy side effects in cancer patients. Data shows that starvation-dependent differential chemotherapy is safe, feasible and effective in cancer treatment, but the possible side effects of starvation limit its efficacy. However, further studies and clinical trials may result in its implementation in cancer treatment.
Keywords: Starvation; Dietary restriction; Differential stress resistance; Differential chemotherapy; Nutrient-signaling pathways.
Isn't this, uh, wrong? My understanding was that calorie restriction was very promising in some animals, but that the studies were never positive for humans or large primates.
I'm actually trying out an intermittent fasting diet right now for weight loss. I'm just always skeptical of new fad diets when they start claiming all sorts of health benefits beyond weight loss.
Weightloss. To me, still means in < out. I tried everything (keto, atkins, low carb, high carb, paleo) and intermittent fasting just seems to work for me.
I fast (skip breakfast/lunch and drink coffee) and start eating when I get back home out of work. I love it because I build up a 'caloric buffer', for when something unexpected happens (random cake/donuts/birthday). IF allows me to adjust my calories at the end of the day as I see fit.
I figure I can stick to a diet better when it's only 1 day in 4 when I have to cut calories. Whereas if I was any good at cutting a moderate amount of calories every day, I probably wouldn't need to be dieting in the first place! ;)
That's why I'm hopeful IF might help.
Yes, it will help.
Then I rebalanced slightly by adding more green vegetables (I was eating virtually none), and reduced the portions of each other category by around %30-%50, bringing me about 500 calories below my basal metabolic rate. One slice of pizza, not two, half a sandwich rather than a whole, a salad once every couple days. Even without removing snack foods, changing the amount I put on a plate radically altered my caloric consumption without me really noticing. Now that I'm at a healthy weight (I should note I'm very tall so a healthy weight is 190-205ish for me), I brought consumption levels back up to slightly above BMR, and will probably increase more as I start weight training.
On a side note, soda and Doritos were regular staples in my diet. When I stopped I noticed that there's a sort of "withdrawal" when you stop eating these hyper-engineered processed foods. Might be the brain not receiving the expected jolt of positive feedback from a high caloric treat. Either that or something in processed foods really affects my body chemistry. All I know is that for weeks in the middle the sight of a bowl of Lays made me feel both tempted and queasy.
Also this NPR article [1] seemed to imply 12 hours of fasting per 24 hours would be enough. That's actually simply skipping breakfast which is really easy.
[1] http://www.sciencefriday.com/segment/12/05/2014/you-are-when...
People get fat because they eat the wrong food, of which the effect of making them hungry and eat even more is only one of the many detrimental effects of unsuitable food for us or other animals.
I don't write this to change your mind, but hope that if someone else reads this, at least this might give them some encouragement, so that they might persist through to read about the issue themselves. It really is not easy to swim against the current.
Our bodies are far more than a simple caloric furnace. But luckily fatness, cancer and a myriad of other metabolic diseases resolve themselves once and for all without calorie counting when one starts to eat correctly. That is, plenty of animal fats, meat, eggs and fish, and very little carbohydrates of any kind. Large portions and infrequently. This makes and keeps you healthy, and you cannot overeat even if you try. Simple and elegant, which is always a prerequisite for any correct theory about nature.
"This makes and keeps you healthy, and you cannot overeat even if you try. "
implies that you can make food choices which prevent you from gaining weight, regardless of quantity.
That just happens to be the topic of the article we're commenting on here. It's also the topic of the book Tripping Over the Truth: The Metabolic Theory of Cancer by Travis Christofferson.
I'm not going to argue about the issue here, but I recommend that book for everyone. If nothing else, it's an interesting read for the history of cancer research and the development of chemotherapeutic drugs.
The body is not immune to the law of conservation of energy. If you think you can eat a caloric surplus of any food type and lose weight then you've resigned yourself to not think rationally.
" Large portions and infrequently. This makes and keeps you healthy, and you cannot overeat even if you try. "
the fact is that you can 'overeat' with ANY meal timing frequency or food choice. caloric balance takes precedence over everything else, even macronutrient breakdown is secondary.
You suggest otherwise and you couldn't be further from the truth.
" That is, plenty of animal fats, meat, eggs and fish, and very little carbohydrates of any kind. Large portions and infrequently. This makes and keeps you healthy, and you cannot overeat even if you try. "
Making the claim that it's impossible to overeat on specific foods is absolutely ridiculous.
Counter anecdote: I "got fat" eating slightly too much relatively healthy, mostly home prepared food over a long period of time. I lost weight by noting how much I ate and reducing intake while continuing to eat the same food. I know some people who eat only fast food and maintain a healthy weight because they have a good sense of how many calories they require.
It's probably true that some people eat diets that condition them to eat too much, but you can't simply claim something as broad as "people get fat because they eat the wrong food" and be done with it.
The parent's "in < out" generalization may be broad, but at least it's true.
I'm just too used to seeing extraordinary dietary benefits being promoted for all sorts of fad foods/diets like blueberries, grapefruit, atkins diet, paleo diet, etc... So I felt like pointing out that there was very little in the way of experimental evidence in that paper (I'm from a physics background, love my data).
With any luck this won't be another one of those papers that gets perverted in the press to "Fasting cures cancer!"
And also people confuse normal variations with treatment consequences, so perhaps the persons in the treatment group classify that as an improvement and the persons in the control group classify that as normal. [2]
In this case, perhaps the comparison is worse because fasting has some side effects and you can get answers like: "I fell a little dizzy, but not as dizzy as the previous week while I was fasting." Should you classify that as an improvement?
[1] Is it possible to do a double blind experiment for this?
[2] Do they have control group?
In studies like this, there is no proof, there is only evidence for different arguments.
In terms of your intermittent fasting diet. Meal timing won't really affect weight loss, what will affect weight loss is your overall energy balance (deficit or surplus), and to a lesser extent macronutrient intake (possible slight fat burn from thermic effect of feeding with higher protein).
There is a guy who did a nice work summarising the scientific findings.
http://www.lift-heavy.com/intermittent-fasting/
Many studies are on animal subjects, but there are human studies too which show more than just weight loss
Calorie restriction in humans is associated with weight loss, reduced inflammation and improved markers for cardiovascular and metabolic health in obese (9,10) as well as non-obese (11,12) subjects
In another study, fasting healthy men and women were compared to a matched non-fasting group with regard to inflammation markers and blood lipid status (61). No differences were observed in body weight, total cholesterol, triglycerides or LDL levels. There was however an increase in HDL levels and decreased inflammation – proposing a beneficial effect in the fasted subjects.
In obese subjects, a modified 8-10 week alternate-day fasting regimen resulted in weight loss, reduced blood pressure and heart rate, and improved markers for cardiovascular health, such as decreased total cholesterol, decreased LDL and triglycerides, increased HDL concentrations and decreased oxidative stress and systemic inflammation, suggesting that alternate-day fasting might be a novel strategy for decreasing body weight and improving cardiovascular health in the obese population (64,68).
eight healthy men were maintained on a 20h modified alternate-day fast for two weeks. Despite unaltered body weight and habitual physical activity, insulin dependent glucose uptake increased, and increased adiponectin levels were observed (65).
In another trial, the insulin sensitizing effect of true alternate-day fasting was observed through reduced insulin response to a standardized meal in men, but not women – suggesting a potential sex difference in the effect of alternate-day fasting on glucose metabolism (66).
I'm also doing intermittent fasting - a 36 hour fast each week - and plan to do longer fasts maybe every 3-4 months - for health reasons.
I'd have to dig in to those specific studies to show that, but don't read an abstract and think that it in any way tells the whole story.
http://www.marksdailyapple.com/fasting-weight-loss/
The above is a good meta-resource on how and why IF helps you eat less.
To get a quick therapeutic effect of starvation, the starvation has to endure several days. During that time the patient drinks water and doesn't ingest any calories at all. There are no exact rules, but after about 4 days the therapeutic effects kick into action, and about 7 days is the maximum. After that the starvation starts to make more harm than good.
This is not easy for a normal person accustomed to a western diet, let alone for someone going through chemotherapy. For someone who already eats correctly (see my other comment in this thread) it's not such a big deal. But then again, you don't see those people on cancer wards as patients too often.
As the saying goes, the best way to beat cancer is not to get one. And for that intermittent fasting is outstanding. In practice it means you eat one or two large portions of food a day. Between the last one of today and the first one of tomorrow should be about 16 hours, give or take. This gives you constant daily beneficial effects of fasting, and once you get accustomed to it and eat the right food, it feels great.
Some recommend a couple of 4-6 days fastings a year on top of this. It's a piece of cake for someone who has practiced such eating habits for some time.
There are plenty of people on cancer wards who had perfectly healthy diets. Most of them are old, because cancer and cardiovascular disease are both primarily diseases of age. There are also cancers like brain cancer, most of which just show up because you were unlucky, not because of any environmental or genetic risk factor. Finally there are plenty of cancers that run in the family like, oh, breast cancer.
So there are tons of people on cancer wards who ate perfectly healthy diets.
Yours, with codial loathing
I also disagree with you that cancer is primarily a disease of age (or ageing). Age is a contributing factor because the longer one lives, the larger the integral of the contributing effects are. Cancer usually takes quite a long time to form and develop so bad that it starts to cause symptoms.
I agree with you that my tone was too harsh. This is a dear subject for me, and I seldom argue about it, because it's so frustrating. I really have no clue why so much hostility arises around this and dieting in general. Maybe because it's so personal and important for all of us. And so, so hard to study by changing only one variable at a time.
So sorry about my harsh tone. Didn't mean to guilt any cancer patients.
This comment makes it seem like you believe the majority, maybe even the large majority, of cancers are caused exclusively by poor diet.
"Exclusively" is a tad too strong, but other than that what you said is exactly what I believe. And it's not only a belief, it's based on research and evidence that's publicly available.
To my best knowledge cancer reasearch by and large is off tracks, and it's the aberrant metabolism of cancer cells (which has been known for decades and is not controversial, even PET scanners operate on that principle) that should be studied more. And that's highly linked to diet as well.
I'm more interested in not getting cancer in the first place, and here I believe diet is the key. I know there are many people who died of cancer and thought the same way, but then again, I operate on the logic I stated in the first paragraph. I expect more evidence starts popping up during the years and decades ahead. The results of mainstream ideology are not at all convincing, and to me it seems hard evidence supports the metabolic theory.
You should probably try reading the article, since the entire thing deals with the science of fasting and starvation and they talk about everything from intermittent fasting to multi-week starvation diets. 72 hour fasts, alternate day fasting, and IF provide the greatest return for the least physiological cost (in that order).
I'm not sure there's anything useful here.
When starved, normal cells 'harden up' so to speak, whereas the cancer cells continue business as usual. When the chemo is administered, normal cells aren't as easily destroyed, but the cancer cells are.
http://en.wikipedia.org/wiki/Heat_shock_protein
As I said before, these proteins are made not just from heat exposure, but from other stress such as fasting and extreme cold exposure. Anyway, I think it is interesting as there is a reasonable amount of ancient literature linking fasting with health(for instance, Isaiah 58:8). Interesting how long science can take to "rediscover" certain basic things the ancients picked up on.
Imagine a TV scene where the hero starts yelling 'get down' in a crowded area before a gunfight breaks out. The 'bad guys' stay upright and the confused civilians duck, so fewer civilians get shot.
IANABiologist
It may be worthwhile to conduct more studies in this direction. I'd be interested to know how soon after the patient stops eating will be the maximum difference in response between normal and cancer cells. And if this is more effective for short chemo treatments, or for the longer ones.