A Paleo Pregnancy Pitfall?

Posted by on September 22, 2011 29 comments

On Saturday’s Around the Web I linked to a study [1] that tied low-carb dieting early in pregnancy to obesity in the child at age 9. This made Ana concerned:

I’m somewhat worried about the pregnancy diet study. Actually I am trying to conceive, 3 months ago my husbund and I changed my diet to Paleo.

Now I see this study and even though I feel great, better than before, I’m not sure, how much credibility would you give it?

I presume that perhaps there could be too little fat, and with that too low calorie intake for a pregnant woman, perhaps that could be the case, opinions please!!!

We certainly don’t want Ana to be stressed out, and it’s hard to turn down three exclamation marks, so I thought I’d interrupt the cancer discussion to address her concerns.

The Study

The study [1] claimed two things:

  1. Women who ate less than a thousand carb calories per day during the early part of pregnancy were more likely to give birth to babies with an overly silenced gene for the Vitamin A receptor RXR-alpha.
  2. Babies born with an overly silenced gene for RXR-alpha were more likely to be overweight at age 9.

Let’s look at the second point, which is more solid, first.

RXR-alpha silencing is associated with obesity

Here is the data:

It looks like it’s normal to have about 50% RXR-alpha methylation in this promoter region and if you have 80% methylation, you’re likely to become a pudgy 9-year old.

How solid is the correlation? They replicated it in a second cohort. Their first study produced two epigenetic marks that were strongly associated with childhood obesity, RXR-alpha and eNOS. A replication study confirmed the RXR-alpha but not the eNOS association.

How plausible is it that RXR-alpha silencing would contribute to obesity? Very plausible, because RXR-alpha is the hub of a network of genes regulating most aspects of metabolism and cell activity.

Vitamin A binds to two types of nuclear receptor, RAR and RXR. When it binds to RXR, a vitamin A – RXR complex is imported into the nucleus. This then looks around for a partner. Partners of RXR-alpha include:

  • Vitamin A – RAR complexes.
  • Vitamin D – VDR (vitamin D receptor) complexes.
  • T3 thyroid hormone – TR (thyroid hormone receptor) complexes.
  • LXR (liver X receptor).
  • CLOCK, the circadian rhythm regulation gene.
  • PPAR-gamma (peroxisome proliferator-activated receptor), a regulator of lipids whose deficiency leads to high cholesterol and hyperglycemia.
  • MyoD, a factor that triggers muscle creation.
  • Many others; a list can be found at Wikipedia.

The vitamin A – RXR-alpha complex “dimerizes” with these other nuclear receptors, forming a new complex that acts as a transcription factor to turn on gene expression. Most of those other partners cannot act to turn on DNA transcription unless they dimerize with RXR.

This means that the absence of RXR-alpha would be functionally equivalent to being low in vitamin A, vitamin D, T3 thyroid hormone, CLOCK, and all those other partners. It is like being born a sun-starved hypothyroid with messed up circadian rhythms who can’t form muscle and is hyperglycemic and dyslipidemic.

All of those things are associated with obesity.

RXR-alpha silencing might be a universal component of the metabolic damage in obesity:

[A]n association between increased RXRA methylation and adiposity is consistent with the observation of strongly diminished RXRA expression in visceral white adipose tissue from obese mice (35).

Personally, I think it’s very likely that silencing of RXR-alpha promotes obesity. This is the most solid part of the paper. They have data, and the mechanism makes sense.

Conclusion: some babies are getting off to a bum start in life due to epigenetic silencing of an important gene.

Does maternal diet affect RXR-alpha silencing?

This is the really weak part of the paper. Here was their data:

When I say this was their data, this was all of it. No scatter plots, no information about how other characteristics of the diet correlate with RXRA methylation, no information about health or lifestyle characteristics of the various carbohydrate intake cohorts so that we can evaluate the possibility of confounding factors.

It is unlikely that low carbohydrate intake was causing the problem. Aside from the fact that dietary carbohydrate intake is only weakly correlated to any factors seen by the baby in the womb (eg blood glucose, insulin, etc), 261 g/day is a substantial amount of carbohydrate – well above physiological needs. So the low-carb quartile included women in glucose deficiency, glucose moderation, and glucose excess; the other quartiles only women in glucose excess. If a glucose deficiency caused RXRA hypermethylation and glucose excess caused RXRA, there would have been a much larger scatter in RXRA methylation levels among the low-carb quartile compared to the 3 higher-carb quartiles. But we can see from the graph that the standard deviations are the same in every quartile.

So there is likely to be some other factor besides carbohydrate intake that was responsible for the RXRA hypermethylation. What are the possibilities?

One possibility alluded to in the paper is that the women had low carbohydrate intake because they were starving. The paper notes that “famine during pregnancy is associated with obesity in the adult offspring (5).” However, I am unaware of recent famines in Southampton UK.

Another possibility is an excess of some other macronutrient. Those mothers who ate fewer carbs were eating more fat and possibly more protein. Given the ubiquity of vegetable oils in modern fats, the increased fat was probably largely omega-6. This raises two possibilities:

  • High maternal omega-6 intake causes RXRA methylation.
  • High maternal protein intake causes RXRA methylation.

Both possibilities have support from studies in rodents: maternal high protein intake and maternal omega-6 fat intake are both associated with obesity in offspring. For more on the risks of high protein, see The Danger of Protein During Pregnancy, Jul 12, 2010.

Another possibility is that the low-carb high-fat diet produced a vitamin A excess. As we discuss in the book, this is a common problem, especially among people taking a multivitamin; probably due to widespread vitamin D and vitamin K2 deficiencies, large numbers of people exhibit evidence of impaired health with vitamin A intake above 10,000 IU/day. As a fat-soluble vitamin, vitamin A intake is more or less proportional to fat intake.

If a balance between vitamin D and vitamin A is needed because the vitamin D-VDR complexes and vitamin A-RXR complexes have to be in proper proportion, then the body may respond to an excess of vitamin A and a deficit of vitamin D by upregulating VDR expression and downregulating RXR expression. Such downregulation may be achieved by RXR-alpha methylation.

Another possibility is some confounding factor that happens to be correlated with carbohydrate intake. In the US Nurses Health Study, nurses with the lowest carbohydrate intake were “rebels” who rejected not only the health advice to eat vegetable-rich and whole-grain rich diets, but also every other standard bit of health advice. The low-carb nurses smoked more, exercised less, and drank more alcohol and more coffee.

So it could be maternal smoking, lack of exercise, or drinking too much alcohol or caffeine that causes RXRA hypermethylation and childhood obesity.

Another possibility, raised in the comments by Amber, is that mothers of the obese children were obese themselves, ate low-carb diets for weight control reasons, and passed on their obesity to their children. It is indeed the case that obese mothers tend to have children who are obesity-prone, and it is suspected that epigenetics may be responsible for this “inherited” obesity. If low-carb diets have indeed become popular among the obese mothers of Southampton UK, then this is a possibility that must be considered.

Low-Carb Paleo Pitfalls?

Should Ana modify her diet because of this study?

I think it’s important to avoid a glucose deficiency. But I don’t think it’s necessary to eat 1,000 calories per day of carbs to achieve that.

I think it’s important to eat a moderate amount of protein, neither too much nor too little; and to limit the amount of omega-6 fats eaten.

I think it’s a good idea to avoid alcohol or excessive consumption of bioactive beverages like coffee during pregnancy. Also to avoid smoking, and to get some exercise and sun exposure.

If you’re doing all these things, I don’t think you need to be concerned. Ana says, “I feel great, better than before”; that’s good evidence that she’s well prepared for a healthy pregnancy.

Conclusion

The paper presents solid evidence that hypermethylation of RXR-alpha in the womb predisposes children to become obese at age 9.

The paper gives us essentially no evidence at all as to what causes hypermethylation of RXR-alpha in the womb, except that it correlates with low carbohydrate consumption in the women of Southampton UK.

I hate it when journals do this. If you’re going to link carb intake to RXRA methylation, give some real data and analysis. Probably the authors are saving their dietary analysis for a future paper. The carb graph was included as a “teaser” to make the work seem more interesting.

There are many known health dangers which are known risk factors for obesity and which correlate with low carbohydrate consumption in the general population. So until more evidence emerges, I think there’s little here for low-carb Paleo dieters to be concerned about.

References

[1] Godfrey KM et al. Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes. 2011 May;60(5):1528-34. http://pmid.us/21471513.

Chicken Wings

Posted by on September 19, 2011 38 comments

A little while back on the recipes thread Gabrielle asked for breakfast ideas that provided protein and worked around some allergies:

Breakfast has become a source of stress for me. Here is why. I have celiac disease so gluten and actually all grains are out for me (except a little white rice which is why this program appeals to me so much). I really need quality protein in the morning to feel good all day but since my diagnosis I over ate eggs and am now allergic to them as well. I have tried bacon and sausage but no matter how organic they are they just don’t sit well in my system. And, whey protein is out for me since I am also allergic to dairy (so just in case you were keeping score I am allergic to gluten, grains, eggs, and dairy).

So, does anyone know of any recipe that might work for me in the mornings?

I suggested chicken wings. These are easy to make in large batches, last a long time, can be eaten cold or microwaves, and make a great party or lunch box food.

It seems only fair to provide our recipe.

Preparing the Chicken

Chicken wings can be purchased either pre-cut or whole. We used to buy them whole, but cutting whole wings into drumettes, wingettes, and tips with kitchen shears tripled the amount of work, so now we buy pre-cut drumettes and wingettes.

After they’re cut, the next step is to rinse the drumettes and wingettes and strain the water, letting them drip-dry for 5 to 10 minutes until they are just moist enough to hold a rice flour coatingpat the wings dry with a paper towel and then let them air dry for ~20 minutes.

The next step is to coat them with a layer of starch, plus salt and pepper also if you haven’t already done that. We do this by putting ¼ cup (4 tablespoons, 60 ml) rice flour in a ZipLoc bag with 25 wing pieces and salt and pepper to taste. Shake the bag until the wing pieces are evenly coated.

Rice flour works better than tapioca starch or potato starch, as it is the least likely to stick to the cooking pan.

Spread the coated wing pieces on an aluminum foil covered cookie sheet:

If you used potato starch or tapioca starch, the aluminum foil will need to be greased with butter to prevent sticking.

Put the cookie sheet in an oven pre-heated to 400ºF (200ºC) for 20-25 minutes. At this point they should look like this:

Flip each wing piece over and return to the oven for another 20-25 minutes. At that point the chicken will be fully cooked:

UPDATE (February 2013): We’ve continued our experiments with chicken wing preparation and have come up with a few refinements:

  1. Using gluten-free flour composed of a mix of rice flour, potato starch, and tapioca starch works better than any single flour or starch.
  2. Because of concerns over aluminum contamination, we’ve experimented with other cooking surfaces. We’ve had excellent results with Pyrex baking dishes:
  3. In cases when the chicken wings seem not as fresh, we’ve taken the precaution of boiling the wings in water flavored with ginger-root and salt (both antimicrobial):

    They can be boiled for 5 minutes and then transferred to a baking dish to resume the above recipe:

    Or they can be boiled for 20 minutes and then pan-fried briefly with the sauce to brown them. This cuts the preparation time in half. This batch used a Chinese sauce (garlic, scallion, ginger, and soy sauce):

Dressings

We made several flavors:

  • Garlic, parmesan, and mustard.
  • Buffalo style.
  • Pacific sweet and sour.

For garlic, parmesan and mustard wings, we mixed 2 cloves diced garlic, 3 tbsp butter, and 1 tbsp mustard at very low heat in a wok. Then we added 1 tbsp brown rice syrup, salt and pepper. When the chicken wing pieces were fully cooked, we added them to the wok, mixed everything thoroughly, and sprinkled parmesan cheese on top. They looked like:

For buffalo style, we combined 4 tbsp butter, chili powder and paprika to taste, garlic, salt, pepper, ¼ cup rice vinegar (or another vinegar), and 1 tbsp brown rice syrup. It looks like:

For Pacific sweet and sour sauce, see Pacific Sweet&Sour Salmon, Apr 10, 2011.

Conclusion

Chicken wings can be a bit time-consuming due to the 45 minutes of oven-cooking, but they are really easy. The chicken wings taste great and they make great finger-food and leftovers.

We typically prepare about 75 and eat them for dinner once and then for snacks over the course of the following week.

Around the Web; Return of the Carbs Edition

Posted by on September 17, 2011 48 comments

A reminder: Shou-Ching and I will be at the Locavore Dinner, hosted by Denny and Aimee Perrin at the Wrap-Around Cottage, 254 Cider Hill Road, York, Maine, later today (September 17). Contact information may be found here. A pot-luck dinner starts at 5 pm; bring “a dish to share consisting of locally-sourced ingredients of animal and/or vegetable origins.” After dinner, I’ll give a talk describing our diet and the logic behind it. All are welcome.

[1] Interesting posts this week: Dr. Kurt Harris was interviewed on the Robb Wolf show. Kurt reports that he got healthier when he went from VLC to 15% carbs, and that lately he’s been eating 40% carbs from safe starches, and doing fine. Some interesting observations: Kurt thinks that problems with legumes are more commonly due to FODMAPs than toxins (and thus problems are gut flora dependent). He says that peaches give him problems due to polyalcohol sugars such as sorbitol.

Remember when Sean at Prague Stepchild was “taking on” Stephan Guyenet?  He’s surrendered.

Pål Jåbekk had a nice post on Carbs and cancer – a good primer for our cancer series.

Lucas Tafur has moved to a new site, plans to broaden his scope, and begins with a nice post: The “Old Friends” Hypothesis.

Craig Newmark reminds us that no one appreciates your health as much as you do, so you should try to take care of it yourself. Bruce Charlton says that science has gone from maximum to minimum honesty.

Eggs or chickens: which poisoned us first? Dr. Michael Greger, a vegetarian, argues that eggs are bad for us, and that eating chicken may lead to a smaller penis. But Dr. Oz says that eating eggs will extend your life.

Bon Appetit says gluten-free is the hottest new health trend: “Physicians are swearing that their own fatigue and brain fog lifted” after they gave up gluten, says Peter H. R. Green, M.D., director of the Celiac Disease Center at Columbia University. “We don’t know the mechanisms for this. It’s fascinating.”

A new blog about living Paleo on little money: A Slim Winter. “[T]his is borne from desperation, frustration and anger…. We have used up all of our savings and now are living just on our unemployment check.  Those checks stop in seven more weeks.  It’s crunch time.”

[2] No, it’s not love: Sea otters hold hands to keep from drifting apart while sleeping.

Via Yves Smith.

[3] A surprising cure for tinnitus?: Todd Hargrove (How to Do Joint Mobility Drills, July 26, 2011) taught us about brain maps, and how a re-mapping the brain can cure phantom pain and improve mobility.

Well, it turns out the brain has maps for sounds also, and tinnitus is “phantom hearing.” Re-mapping the brain may cure tinnitus:

“We argue that reorganizing the cortical map should be the goal, so that the nerves get some input and stop their tinnitus activity,” he said. “You don’t want to leave these cells without sensory input.”

“We changed our (brain training) strategy from one where we completely avoided the tinnitus domain to one where we directly engage it and try to redifferentiate or reactivate it, and we seem to be seeing improvement,” Merzenich said.

[4] Cook your food gently: By testing the hearts of old mice for oxidative agents in mitochondria, researchers found that acrolein, which is generated when glycerol is heated to 280ºC, was responsible for most of the aging damage.

Chavez JD et al. Site-specific proteomic analysis of lipoxidation adducts in cardiac mitochondria reveals chemical diversity of 2-alkenal adduction. J Proteomics. 2011 Apr 13. [Epub ahead of print] http://pmid.us/21513823.

[5] Pretty: Jack Brauer of WideRange.org photographs Plitvicka Jezera National Park in Croatia:

Via the Daily Mail.

[6] Do maternal low-carb diets make children fat?: In mice, mothers eating low-carb high-protein diets give birth to offspring prone to obesity. Some evidence has emerged indicating that something similar may happen in humans.

In a new study, women who ate a “low-carb” diet – 1,000 calories per day or less – early in pregnancy were more likely to give birth to children with hypermethylation (epigenetic silencing) of the retinoid X receptor-alpha (RXRA) gene. This is the most important receptor for vitamin A.

The more RXRA was silenced, the more likely children were to become obese. By age 9, children in the highest quartile of RXRA methylation at birth were significantly fatter than children in the lowest quartile of RXRA methylation.

Godfrey KM et al. Epigenetic gene promoter methylation at birth is associated with child’s later adiposity. Diabetes. 2011 May;60(5):1528-34. http://pmid.us/21471513.

See also:

Reynolds RM et al. Maternal BMI, parity, and pregnancy weight gain: influences on offspring adiposity in young adulthood.  J Clin Endocrinol Metab. 2010 Dec;95(12):5365-9. http://pmid.us/20702520.

Pollin TI. Epigenetics and diabetes risk: not just for imprinting anymore? Diabetes. 2011 Jul;60(7):1859-60. http://pmid.us/21709282.

[7] Perfect Health Hummus?: Anyone who wants to eat more carbs is going to need more “safe starches.”

One of the more popular legumes worldwide is chickpeas, the main ingredient in hummus. A number of commenters – Andrea Reina, Ruth of Ruth’s Real Food, and Beezneez – gave us instructions for achieving this. Here are Ruth’s detailed instructions. You need acid, potatoes, overnight soaking, and thorough cooking.

[8] Shou-Ching’s Photo Art:

[9] Video of the week: Catherine Destivelle performs an amazing solo climb in Mali:

Via UKClimbing.com.

Toward an Anti-Cancer Diet

Posted by on September 15, 2011 47 comments

Since starting the blog, I’ve gotten a number of emails from cancer patients or their family members. When the Q&A page started last week, the second question was from Lindsay, asking for a cancer diet:

In the past 3 weeks my partner has been diagnosed with stage 3 breast cancer. She is 28 and there is no family history….

Do you have suggestions aside from vit d and green tea that might be therapeutic?…

In my mind she simply needs to be extremely well nourished, but that is proving tricky due to nausea. I made a batch of chicken broth the other day and the smell alone sidelined her. Any thoughts on a way to sneak in dense nutrients without a strong odor?

I’ve delayed blogging about cancer and diet because of the complexity of the issue. Research has not yet determined the optimal diet for cancer patients, and there is reason to believe that the optimal diet may differ for different cancer patients. It is not easy to balance the many factors that should influence a cancer patient’s diet.

Today I’ll lay out my general perspective on cancer. The goal is to identify aspects of the disease that we can influence through diet. In subsequent posts, I’ll discuss foods, nutrients, and eating strategies. I hope the manner in which I’m addressing the issue will help cancer patients to understand the issues better and to design an effective personal eating strategy.

Cancer as a Progression of Diseases

Cancers often develop over long periods of time – typically decades. They usually cannot be detected or diagnosed at early stages. This is just as well, because most early cancers resolve spontaneously; they disappear or return to a normal state. Perhaps we should have a distinct name for these early and usually harmless cancers – “proto-cancers” perhaps.

Proto-cancers develop through a series of stages into life-threatening cancers. At each stage, the character of the disease changes. The purpose, and perhaps the nature, of dietary interventions may change with it.

Origins of Cancer

What characterizes these proto-cancers is that one or more cells develop an abnormal state of gene expression that I’ll call the cancer phenotype.

What causes a cell to develop the cancer phenotype? I believe the most common are:

  1. Infections, especially viral infections (since viruses are good at modifying gene expression).
  2. Toxins, especially DNA-modifying toxins such as those generated by peroxidation of polyunsaturated fats.
  3. Malnutrition, especially nutrient deficiencies that impair the ability to maintain epigenetic regulation of DNA.

The Wikipedia page “Infectious Causes of Cancer” says that 18% of human cancers are known to have infectious causes, but I suspect the fraction will get much larger. Read through our story of XMRV and chronic fatigue syndrome (“Retroviruses and Chronic Fatigue Syndrome, Aug 24, 2010) for an example of how difficult it is to identify the viruses that cause cancers. In this instance, a new human retrovirus may (it is still disputed) have been discovered because men with genetic impairments to anti-viral immunity have much higher rates of prostate cancer, and scientists searched prostate tumors of men with this genetic impairment for viruses. If finding the cancer-causing virus is so difficult when we know it is present in the tested tissue, you can easily imagine how many other viruses may have escaped scientific notice.

Interventions to prevent the original causes of cancer are great for cancer prevention, but they may also be therapeutic. Removing cancer-causing viruses may enable the body to defeat a cancer it otherwise could not.

Proto-Cancers and the Evolution of Cancer Cells

The cancer phenotype has various characteristics, but at early stages important characteristics may include:

  • Suppression of mitochondrial activity, especially apoptosis (programmed cell death).
  • Metabolic changes toward metabolism of glucose and away from metabolism of fatty acids or ketones.
  • Isolation of the cell from the rest of the body. Normal human cells closely coordinate their activities with the rest of the body, especially with neighboring cells, and respond to hormonal and other signals. Cancer cells tend to be more “individualistic,” less responsive to the body and to their neighbors.

Every once in a while one of these cells with a cancer phenotype will divide, creating two daughter cells. Perhaps in part because after metabolic impairment the cell has difficulty providing sufficient ATP to handle the complex motor tasks involved in cell division, these cancer cells often fail to divide properly, resulting in daughter cells with altered genetic state. Common changes include:

  • Aneuploidy. Most genes have two copies, one inherited from the mother and one from the father. In cell division, genes are first duplicated, and then divided among two daughter cells, so that each cell gets two copies. In aneuploidy, chromosomes are improperly separated so that one cell gets three copies of a chromosomal strand, the other one. Genes on that strand then become expressed 1.5-fold in the cell with three copies, half-fold in the cell with one copy.
  • Translocations. Chromosomes have a certain gene order. However, they can be re-assembled in an improper order, with one segment translocated to another place. This changes gene expression.
  • Epigenetic modifications. DNA comes with a protein scaffold that packages and organizes it, and can be modified so that gene expression is silenced (via methylation) or enhanced (via acetylation). Epigenetic modifications are usually inherited by daughter cells – but dividing cancer cells may experience less stability in the epigenome.

These changes mean that cell division causes cells with a cancer phenotype to evolve. Let’s say aneuploidy occurs affecting a gene that stimulates cell division. One daughter cell gets 3 copies and becomes more likely to proliferate; the other cell gets only 1 copy and becomes less likely to proliferate. Of course, every time a cell divides it creates two daughters, so a decade later the first cell may have thousands of descendants while the first cell has few. A proliferative phenotype has become more common in the “tumor.”

The Middle Stages of Cancer Development

As a result of cellular evolution, the early cancer phenotype becomes a later cancer phenotype with new traits, such as:

  • A tendency to proliferate. This is the trait people most commonly associate with cancer cells.
  • A tendency to stay alive indefinitely. Some cancer cells become “immortal.” For instance, HeLa cells are immortal cells taken from the cervical cancer of Henrietta Lacks, who died in 1951. So resistant to death were these cells, they were the first human cells ever to survive in vitro.

Both traits are promoted by infections. Viruses and other germs want to stay alive, and to do that they need to keep their host cell alive, since cell death typically kills any germs in the cell (thus programmed cell death is a major part of human immune defense). Viruses also want to replicate, and to do that they often piggyback on human DNA replication. So viruses have evolved ways to promote proliferation and immortality of host cells. Cancers caused by viruses, therefore, often have a head start on acquiring these traits. Cancers that appear at young ages are probably almost always viral in origin.

Once these traits are acquired, the cancer cells proliferate and form a tiny tumor. These micro-tumors can reach a size of about 0.5 mm in diameter. At that point, growth stalls for lack of oxygen and nutrients. Cells inside the tumor cannot get enough resources to continue their growth.

Often this is the end of the cancer; it never develops beyond this point. It’s been estimated that most adults have thousands of these microtumors, and most never go on to develop clinical cancer. It is generally impossible to diagnose the presence of these microtumors.

However, cells in the microtumor are still evolving. Cells, when nutrients are available, divide, and one daughter cell survives to divide again while another cell in the tumor dies to make room. There is a “survival of the fittest” contest in which cells become more adapted to the environment of the tumor.

Progression to Diagnosable Disease

At some point, one or more cells may gain the ability to manipulate neighboring cells to their own benefit. This is a crucial stage in the development of cancer: when the cancer phenotype extends to give the tumor new abilities to exploit its human host. A key capability is:

  • the ability to induce the formation of blood vessels. This process is called angiogenesis.

This process involves manipulation of the immune system, which is responsible for wound healing as well as defense against foreign bodies. Angiogenesis is part of the normal wound healing process, and when it becomes angiogenic, a tumor (in the famous phrase of Hal Dvorak) becomes a “wound that never heals.” That is, it acts like a wound to call forth the blood vessel generation process, but it never allows the wound healing process to terminate.

Once cancer cells can call forth new blood vessels from surrounding tissue, they have access to all the body’s nutrient and oxygen resources. There is no longer any limit to the tumor’s growth. This evolution of an angiogenic capability could be said to create the disease of cancer.

One of the interesting findings of recent research is that foods can significantly influence the likelihood that tumors will develop an angiogenic capability. A number of plant compounds from foods such as garlic, tomato, green tea, and turmeric have been shown to inhibit angiogenesis. If you read the excellent book Anti-Cancer by David Servan-Schreiber, you’ll find that these anti-angiogenic foods form the essence of his dietary advice.

Once tumors can induce angiogenesis, they can grow quite large. But even large single tumors are usually not deadly.

Progression to Deadly Disease

Cancers become deadly when another change evolves:

  • Some cancer cells become metastatic.

Metastatic cells migrate away from the tumor, interact with non-cancer cells, and may travel through the blood to distant sites where they establish new tumors. When cancer metastasizes, many tumors can develop and the cancer can become a devastating drain on the host.

Immune Suppression and Co-Infections

Other new cancer capabilities may also evolve. For instance:

  • Suppression of anti-cancer immunity.

When the immune system successfully attacks and destroys cancers, it is usually through an innate immune response involving natural killer cells and macrophages. Interestingly, this is also the same immune response which defends against fungal infections.

One of the interesting aspects of the evolution of cancer cells is that they often end up with many genes silenced, such that they lose many distinctively “human” genes and probably come to resemble our primitive evolutionary ancestors. In other words, cancer cells evolve to look more like fungal cells, so that a tumor may biologically resemble a mold colony.

Suppose cancer cells evolve a capability to suppress the NK cell and macrophage immune response. Then the tumor will flourish more readily – but so also will fungal infections.

It happens that late-stage cancer patients commonly develop systemic fungal infections.

It also works the other way: fungi that have evolved into obligate parasites of human hosts, like Candida, are good at suppressing human anti-fungal immunity. In doing so they also suppress human anti-cancer immunity. Thus, fungal infections are a risk factor for cancer. I saw a study recently in which a large fraction of people treated for systemic fungal infections were diagnosed with cancer in the following five years.

There is evidence that fungal infections of cancer cells increase the rate of metastasis. So the combination of cancer and fungal infections may be particularly deadly. This suggests that cancer patients might benefit from anti-fungal therapies.

There may be great variability in human immunity against cancer. Biologist Zheng Cui has found such variability in mice, and estimates that 10-15% of humans may be highly resistant to cancer. It is likely that diet can modulate this resistance, which suggests looking for dietary tactics that promote anti-cancer immunity.

Cachexia and Anorexia

Cachexia is the wasting syndrome that afflicts late-stage cancer patients. The tumors become a large drain on resources, their nutrient consumption is not met by diet, and the rest of the body is cannibalized in order to provide resources to the tumors. Muscle and other tissue wastes away until they can no longer sustain life.

Cachexia is often what kills cancer patients.

Now, if the cancer patient could eat sufficient food, even very large tumor burdens might be tolerable. Olympic swimmers eat 12,000 calories a day; pregnant women support 8 pound growths in their abdomen without risk.

Unfortunately, cancer also tends to diminish appetite. One of the consequences of cancer’s interactions with the immune system is that late-stage cancer generates a lot of inflammatory cytokines which can be imported into the brain where they affect the food regulatory systems that Stephan Guyenet has written about, causing anorexia.

Cancer-related anorexia makes food distasteful and causes cancer patients to cease eating. Lindsay mentioned her partner’s anorexia as one of the problems she hoped I could help her address.

Exercise and dietary strategies that promote muscle and tissue growth (“anabolic” strategies) such as those employed by bodybuilders and strength athletes might increase appetite, protect tissue, and delay the negative effects of cachexia. They might also have an anti-cancer effect by depriving the cancer of resources.

Interaction with Chemotherapies

Yet another complexity is that the standard therapies for cancer involve poisoning the body with chemotoxins.

This raises a conundrum. A healthy diet makes the body, and all its cells including cancer cells, more resilient to toxins. So a healthy diet may undermine the effectiveness of chemotherapies.

Some diet-chemotherapy interactions are well documented. Supplementation of vitamin C, glutathione, and omega-3 fats are all known to protect cancer cells against chemotherapies.

If beneficial foods reduce the effectiveness of chemotherapy, it might also be the case that toxic foods could increase their effectiveness. Thus, the optimal diet during chemotherapy might be quite different from the optimal diet when off chemotherapy.

I will not say much about these interactions, other than to advise that before undergoing chemotherapy cancer patients discuss their diet and supplement regimen with the oncologist.

Summary: Our Path to an Anti-Cancer Diet

So, we’ve identified a number of possible levers for attacking cancer. We can look for dietary steps to:

1)      Defeat viral or other infections that originally caused the cancer.

2)      Remove toxins and improve nutrition in order to promote DNA and epigenome stability.

3)      Deprive cancer cells of their favored glycolytic metabolic pathways, slowing their growth.

4)      Restore mitochondrial function, promoting apoptosis (programmed cell death) of cancer cells.

5)      Inhibit angiogenesis.

6)      Inhibit metastasis.

7)      Promote anti-cancer and anti-fungal immunity.

8)      Mitigate anorexia and cachexia.

Those who are trying to prevent cancer will want to focus on (1)-(5); those with early stage cancers on (1)-(7); those with late stage cancers on (1)-(8).

Our mission: understand how diet and nutrition can affect each of these; and then try to integrate various dietary tactics into an optimal anti-cancer strategy.

Conclusion

I think this gives us plenty to work on. Next week, I’ll provide short provisional answers. Over the next year, I’ll examine each type of cancer-diet interaction in detail and see if we can refine and improve our anti-cancer strategy.