It’s hard for me to hear about Omega-3′s (EPA and DHA) and not think of Alice and Fred Ottoboni’s work in this domain. They’ve done more to help me understand the importance of these substances than anyone else, and it’s hard to consider their book, Modern Nutritional Diseases as anything less than brilliant.
So it was with great interest that I read this article:
Fatty Acid Metabolite Shows Promise Against Cancer In Mice. I know…I know…another rodent study. And another study touting a cancer cure. How many of these do we have to endure?
Well, probably many. There’s something about this that I find intriguing:
A team of UC Davis scientists has found that a product resulting from a metabolized omega-3 fatty acid helps combat cancer by cutting off the supply of oxygen and nutrients that fuel tumor growth and spread of the disease. [...] The metabolite is epoxy docosapentaenoic acid (EDP), an endogenous compound produced by the human body from the omega-3 fatty acid named docosahexaenoic acid (DHA), which is found in fish oil and breast milk. In animal studies, the UC Davis scientists found that EDP inhibits angiogenesis, the formation of new blood vessels in the body.
[…]
The researchers also found that a metabolite of arachidonic acid (ARA), an omega-6 fatty acid, has the opposite effect of EDP. The ARA metabolite, epoxyeicosatrienoic acids (EETs), slightly increases angiogenesis and tumor progression in mice.
That we should seek out ways to ensure our diets are high in Omega-3′s and low in Omega-6′s won’t be news to most of us. There are many potential health benefits from doing each. However, what intrigues me about this research is that it postulates a precise mechanism by which DHA is protective against (certain types of?) cancer, and how Arachadonic Acid is tumogenic…this is the type of thing that excites me. This, at least, is something testable.
And what of the Ottobonis? And of a ketogenic diet? Well, I’m reminded of their fantastic exploration of fatty acid metabolism in Modern Nutritional Diseases (1st. Edition), where, after a fascinating review of the biochemical pathways of essential fatty acids, eicosanoids, prostaglandins and arachadonic acid (Cox-2 and lipoxygenase pathways) they write:
The tremendous importance of blood glucose in influencing what the biochemistry of the body does with major nutrients (carbohydrates, proteins, and fats) cannot be overemphasized. Blood glucose, the ultimate metabolic product of most carbohydrates, exerts this influence by prompting the pancreas to release the hormone insulin. Insulin, in turn, stimulates the enzymes that cause the sythesis of body fat and cholesterol (Figure 5-1). Insulin also stimulates the production of arachidonic acid (Figure 203), precursor of harmful eicosanoids. As such, insulin is a major contributor to diseases that range from heart disease and stroke to type-2 diabetes and cancer. (MND, 53)
It’s worth noting the date in my edition of Modern Nutritional Diseases: 2002. Chances are, Alice and Fred Ottoboni were on to this even before then.
Resources
- Epoxy metabolites of docosahexaenoic acid (DHA) inhibit angiogenesis, tumor growth, and metastasis, Zhang, Panigrahy, et al. Proceedings of the National Academy of Sciences (PNAS), April 3, 2013, doi: 10.1073/pnas.1304321110.
- Fatty Acid Metabolite Shows Promise Against Cancer in Mice, Headlines and Global News, April 2, 2013.
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The keto brain, coming soon to a disorder near you!
There was a commenter on this page that mentioned the lack of articles on epilepsy and keto on this site. This is a good point! The ketogenic diet has been used for many many years for epilepsy- it is extremely well documented and known. Why have I avoided talking about it?
For one, I would say I perceived a lack of interest in the topic. More people are interested in using this diet for dieting purposes. I would say more people have extra weight to lose than a seizure disorder.
Secondly, I’ve always held a little extra room in my heart for endocrinology, which obesity studies tend to focus heavily on (no pun intended).
This is ironic because I am on the diet myself for my crippling rare migraine syndrome. I was tired of medications and was looking for alternatives. There are some migraine alternative treatments that sound rather horrifying- cauterizing blood vessels and Botox shots to the neck- so I started to think outside of the box. Migraines are in the same class of disorders as epilepsy, and I had often had some success with anticonvulsants. Alternative epilepsy treatments? Yep. Now here I am, migraine free, medication free.
So let’s talk keto and the brain!
Let’s start with the history: In 1911 in France the first patients were treated with diet for their epilepsy. And by diet I mean fasting and low calorie vegetarian diets. When starved, patients had a lot fewer seizures. They also were hungry and adherence to a diet that involved not eating became extremely difficult. So in 1921 Dr. Wilder came up with an alternative: the ketogenic diet. The classic ketogenic diet is a 4:1 ratio of fats:protein and carbs. This diet fell to the skirts of medicine once anticonvulsants hit the market in 1938, but has seen a resurgence of use to treat intractable epilepsy- epilepsy that doesn’t respond to medications, and for people who are interested in being medication free.
There are 4 different forms used to treat epilepsy- the classic, MCT, MAD, and low glycemic index diets. The MCT (medium chain triglyercide) incorporates large amounts of MCT oil- which is most readily turned to ketones by the body. The MAD (modified Atkins diet) is the most common one used for weight loss: 5% carb, 65% fat, 30% protein. The low glycemic index diet maintains similar ratios with only slightly more carbs but focuses on carbs that are low on the glycemic index. All types of these diets seem to have similar efficacy (possibly still slightly better on the classic), despite differing amounts of ketosis produced. The degree of ketosis seems not to be terribly important.
Awesome! Well then, how does it work? What makes ketosis magic?
“The exact mechanism of action of the diet is still unknown
though there are a number of theories and ongoing research.”Maybe another article has the answer?
“The mechanism(s) through which the KD exerts its anticonvulsant effects remains elusive. Although there is an abundance of data regarding the physiologic effects a KD exerts on humans and rodents, how these effects contribute to seizure protection is unclear. The diet has both anticonvulsant (ie, stopping a discrete seizure) properties and antiepileptic (ie, stopping the propensity to develop recurrent unprovoked seizures, or epilepsy) effects.”
Nope. It appears to be a mystery. There’s a whole host of potential suitors, though, and article after article advocating for a particular reason. Here’s a small list:
- antioxidant effects and lowering free radials
- protection against cell death
- anti-inflammatory effects
- GABA vs glutamate, where glutamate is the catnip toy to a bunch of cats and GABA is the morning sunlight and open cardboard boxes (excitatory vs inhibitory neurotransmitters, see this journal article if desiring a less feline version).
Well these things all seem highly nonspecific to epilepsy, actually. They sound like a good combination for a lot of issues (or just normal brains in general). What other brain disorders/diseases get benefit from keto?
Apparently it’s not just me: keto is good for migraines. I’m not in love with this article because it is the briefest of summaries, but there it is.
On autism:
“In this study, the application of a ketogenic diet was highly successful for the two patients with mild autistic behavior, whereas minor or moderate improvement was established in patients with severe autistic behavior.”
A study on ALS in mice showed significant slowing in motor deterioration and protected motor neurons.
Brain cancer may see some benefit from keto.
There are some rumblings about Parkinson’s and Alzheimer’s, the evidence is shaky at best right now.
ADHD mice and depressed mice seemed to do better, more studies needed for sure.
The one that hasn’t been done that I’m waiting on bated breath for is bipolar disorder. Bipolar disorder is the third sibling of epilepsy and migraines, and is treated with anticonvulants as well. So will someone pleeaaaase just do the study already!
Resources
- A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis, Zhao, Lange et al. BMC Neuroscience 2006, 7:29. doi:10.1186/1471-2202-7-29.
- Application of a Ketogenic Diet in Children With Autistic Behavior: Pilot Study, Evangeliou, Vlachonikolis et al. Journal of Child Neurology, 2003 18: 113. DOI: 10.1177/08830738030180020501.
- Ketogenic Diet, Dhamija, Eckert et al. Canadian Journal of Neurological Science, 2013; 40: 158-167.
- Neuroprotective and disease-modifying effects of the ketogenic diet, Gasior, Rogawski et al. Behavioral Pharmacology. 2006 September; 17(5-6): 431–439.
- Short term improvement of migraine headaches during ketogenic diet: a prospective observational study in a dietician clinical setting, Lorenzo, Coppola et al. The Journal of Headache and Pain. 2013 1(Suppl 1):P219. doi:10.1186/1129-2377-1-S1-P219.
- The antidepressant properties of the ketogenic diet, Murphy, Likhodii et al. Bioligcal Psychiatry. 2004 Dec 15;56(12):981-3. Abstract.
- The calorically restricted ketogenic diet, an effective alternative therapy for malignant brain cancer, Zhou, Mukherjee et al. Nutrition and Metabolism, 2007, 4:5 doi:10.1186/1743-7075-4-5.
- The ketogenic diet: metabolic influences on brain excitability and epilepsy, Lutas and Yellen. Trends in Neurosciences, Volume 36, Issue 1, 32-40, 10 December 2012.
- The Ketogenic Diet: One Decade Later, Freeman, Kossof et al. Pediatrics, Vol. 119 No. 3 March 1, 2007. pp 535-543. (doi: 10.1542/peds.2006-2447).
- The ketogenic diet causes a reversible decrease in activity level in Long–Evans rats, Murphy and Burnham. Experimental Neurology 201 (2006) 84–89.
Research Finds Link Between Fructose and Pancreatic Cancer
Ashton Kutcher has been in the news a lot recently. Normally this is something well worth ignoring, but in this instance it’s interesting: He’s been promoting the new Steve Jobs movie (in which he plays Steve Jobs) by explaining how he was hospitalized after following Steve Jobs’ diet for some time. Steve Jobs apparently ate nothing but fruit.
So what happened to poor Ashton? Well, the details are quite thin: “I was doubled over in pain [...] my pancreas levels were completely out of wack.” Media reports that he spent time in the hospital. The exact nature of his affliction and the treatment for it remain undisclosed.
Not really much to go on there, but since it’s in the news, I thought it worth mentioning a fructose-pancreatic cancer connection described back in 2010.
In the paper, Fructose Induces Transketolase Flux to Promote Pancreatic Cancer Growth, the lead researchers to state, “fructose provides an alternative substrate to induce pancreatic cancer cell proliferation.” Of course, we’re acutely aware of the connection between cancer and glucose, but this paper suggests that even though glucose and fructose have long been considered interchangeable in terms of cancer cell metabolism (aerobic glycolosis), in actuality they are metabolized quite differently by pancreatic cancer cells:
…our data indicate that the contribution of fructose to nucleic acid synthesis is considerably greater than glucose and that cancer cells preferentially use fructose via TKT-mediated metabolism to synthesize additional nucleic acids to facilitate increased proliferative capacity. Synthesis of nucleic acids and nucleotides is of utmost importance for proliferating tissues and especially cancers.
The authors go on to describe the precise metabolic pathways at play and assert that their findings are critical in understanding the etiology of pancreatic cancer in light of the massive (over)consumption of sucrose and HFCS we’ve undertaken in modern times.
While not as sexy as a sensationalist movie promotion, it’s heady and important stuff to pay attention to. If you don’t feel like wading through the research, you might find this BBC Interview with Dr. Anthony Heaney (one of the authors of the paper) to be an accessible source.
Research
- Fructose Induces Transketolase Flux to Promote Pancreatic Cancer Growth, Nissen, Heany et al. Cancer Research August 1, 2010 70; 6368
- Pancreatic Cancers Use Fructose, Common in a Western Diet, to Fuel Growth, UCLA Jonsson Comprehensive Cancer Center press release.
- BBC Interview With Dr. Anthony Heaney, Audio/MP3
- Ashton Kutcher Suffers Health Scare Prepping for ‘Jobs’, USA Today, Jan 29, 2013
Cancer As A Metabolic Disease – Thomas Seyfried
Cancer As A Metabolic Disease, by Thomas N. Seyfried
Browse on Amazon!Some people lust after cars, or wealth, or beautiful things. Apparently, I’m demented enough to lust after books.
But what a book…
I’ve been following Seyfried for quite a while now. His talk at Ancestral Health Symposium 2013 (AHS13) is renowned. His research, promising. And his interviews, fascinating.
Cancer As A Metabolic Disease is Seyfried’s treatise on the subject, his omnibus on the subject. In it, he builds upon the concepts first articulated by Otto Warburg (of, “The Warburg Effect” fame) and covers insights gleaned from decades of research in his own lab at Boston College.
Unlike other books in the booklist, I haven’t yet read this one. I can’t quite justify the expense at the moment, but it’s definitely on my list and some day, I’ll figure out a way to get a copy. Until then, it’ll remain on the list as a reminder and a resource to those interested in the subject.
Resources
- Cancer As A Metabolic Disease, Thomas Seyfried
- The Calorically Restricted Ketogenic Diet, An Effective Alternative Therapy For Malignant Brain Cancer. Seyfried, Zhou, et al., Nutrition and Metabolism, June 2007.
- Targeting Energy Metabolism in Brain Cancer – Thomas Seyfried (AHS12)
- Google Scholar Search
- Thomas Seyfried on Jimmy Moore’s Low Carb Conversations With Friends (Podcast)
The Connection Between Sugar and Cancer – A Dana-Farber Podcast
Hillary Wright of Dana-Farber Cancer Institute has a brief podcast on the connection between sugar and cancer.
Play Podcast on Cancer and Sugar
Transcript
We now now realize that there is a lot about diet and lifestyle that can influence the chemical hormonal environment of your body that may potentially be more favorable for the growth and development of abnormal cells.
Chronic excessive intake of simple sugar leads to excess production of hormones like insulin and insulin-like growth factor (IGF) that may encourage the growth of cancer cells.
So when you eat any kind of a carbohydrate, within an hour it’s in your blood as glucose (which is blood sugar).
So if you’re just eating food and your blood sugar goes up, and then it goes down, and then it goes up, and then it goes down…that’s what’s going on with your insulin levels. They are just rolling…
This is the way human beings were designed. Again, we’re hunter gatherers. We got food, we digested it, hopefully we got some more…
But there’s nothing in nature that represents a 20oz coke, a gigantic serving of whatever kind of junk food you’re going to get at a fast food place that has sugar in it that you never even dreamed would be there. We’re just eating way too much sugar.
So the issue is more that nowadays we have people eating a lot of sugar that causes these big spikes in their blood sugar and their insulin response. We also have a lot of people who are overweight and sedentary, so they are more likely to be resistant to this hormone insulin. So when the pancreas secretes it to clear the sugar out, it gets in the habit of oversecreting it.
So it’s the excess circulating growth hormones, like insulin and insulin-like growth factor and others, that if you have chronic exposure to those things, that’s what we’re worried about having a connection to cancer cell growth.
Resources
Why We All Don’t Get Cancer – Memorial Sloan-Kettering Cancer Center
A fantastic talk at Memorial Sloan Kettering Cancer Center by Craig P. Thompson, President and CEO of Memorial Sloan Kettering.
It starts off with a great overview of cancer in general and the associated metabolic pathways of cancer cells, including the Warburg effect and why cancer cells light up in a PET scan (hint, it’s the glucose!). He also touches on the problems of overconsumption leading to increased IGF-1 stimulation and the resultant increase in glucose uptake by all cells. This, of course, drives tumogenesis.
At this point he comes on strong with the nutrition connection:
“If you overfeed someone with fat, you don’t increase their cancer risk at all. If you overfeed someone with carbohydrates, you dramatically increase their cancer risk. Protein is half way in between.” (Craig Thompson)
If we return now to the title, it seems like Craig Thompson’s answer to his rhetorical question, “Why don’t we all get cancer?” is basically, glucose control.
Well worth the watch if you are interested in cancer, or touched by it personally or via friends/family.
Targeting Energy Metabolism in Brain Cancer – Thomas Seyfried (AHS12)
Thomas Seyfried’s talk at Ancestral Health Symposium 2012 (AHS12) is a deep dive into the origins of cancer, loosely framed around the question, “Is cancer a metabolic disease?” In some ways an extremely provocative talk, but fascinating to watch him step through the science behind assertions like, “Regardless of what you might read, mutations are not the cause of cancer.” (Hint: it’s the mitochondria! “We never find completely normal mitochondria in any cancer cells.”)
Some of the concepts he covers include why it’s important to target glucose and glutamine when fighting cancer. It turns out that cancerous cells can metabolize either of these.
Note: If you have trouble with the video below, try viewing it here. It seems like there are some problems with hosting permissions that Vimeo/AHS needs to work out.
Targeting Energy Metabolism in Brain Cancer by Thomas Seyfried at the 2nd annual Ancestral Health Symposium 2012 (AHS12) from Ancestral Health Society on Vimeo.The Role of a Low Carb Ketogenic Diet in the Treatment and Prevention of Cancer – Dr. Rainer J. Klement (AHS12)
A fantastic lecture by Dr. Rainer J. Klement (Medical Physicist) of Lets Go Paleo on the role of a low carb ketogenic diet in the prevention and treatment of cancer. The actual title of the Ancestral Health Symposium 2012 (AHS12) presentation is, “Is there a role for a paleolithic lifestyle in the treatment and prevention of cancer?”, but most of the talk focuses on how a low carb diet implemented with good food quality choices (as are often found in paleo nutrition) can not only prevent cancer, but can be used as part of treatment.
Dr. Klement provides some fantastic overviews of the mechanisms at play (including the history and function of the Warburg effect). This is well worth watching for anyone touched by cancer in any way.
Note: If you have trouble with the video below, try viewing it here. It seems like there are some problems with hosting permissions that Vimeo/AHS needs to work out.
Is there a role for a paleolithic lifestyle in the treatment and prevention of cancer? by Rainer J. Klement at the 2nd annual Ancestral Health Symposium 2012 (AHS12) from Ancestral Health Society on Vimeo.Dietary Insulin Inhibition as a Metabolic Therapy in Advanced Cancer – Eugene Fine, M.D., (AHS12)
A great video of Dr. Eugene Fine discussing the insulin and cancer connection. Another from Ancestral Health Symposium 2012 (AHS12).
Eugene Fine, M.D.—Dietary Insulin Inhibition as a Metabolic Therapy in Advanced Cancer (AHS12) from Ancestral Health Society on Vimeo.