Cancer and the Immune System

My understanding of cancer has changed radically over the past few months. I used to think of it as an inevitable consequence of aging, a stochastic certainty. The human body is made of about 50 trillion cells, many of which replicate their DNA and divide regularly. It's only a matter of time until one of those cells randomly accumulates the wrong set of mutations, and loses the molecular brakes that restrict uncontrolled growth.

Strictly speaking, the idea is correct. That is how cancer begins. However, there's another check in place that operates outside the cancer cell itself: the immune system. A properly functioning immune system can recognize and destroy cancerous cells before they become dangerous to the organism. In fact, your immune system has probably already controlled or destroyed a number of them in your lifetime.

I recently read a fascinating account of some preliminary findings from the lab of Dr. Zheng Cui at Wake Forest university. His group took blood samples from 100 people and purified a type of immune cell called the granulocyte. They then evaluated the granulocytes' ability to kill cervical cancer cells in a cell culture dish. They found that it varied dramatically from one individual to another. One person's granulocytes killed 97% of the cancer cells in 24 hours, while another person's killed 2%.

They found some important trends. Granulocytes from people over 50 years old had a reduced ability to kill cancer cells, as did granulocytes from people with cancer. This raises the possibility that cancer is not simply the result of getting too old, but a very specific weakening of the immune system.

The most important finding, however, was that the granulocytes' kung-fu grip declined dramatically during the winter months. Here's Dr. Cui:

Nobody seems to have any cancer-killing ability during the
winter months from November to April.

Hmm, I wonder why that could be?? Vitamin D anyone??

Celiac and Fat-Soluble Vitamins

One of the things I've been thinking about lately is the possibility that intestinal damage due to gluten grains (primarily wheat) contributes to the diseases of civilization by inhibiting the absorption of fat-soluble vitamins. If it were a contributing factor, we would expect to see a higher incidence of the common chronic diseases in newly-diagnosed celiac patients, who are often deficient in fat-soluble vitamins. We might also see a resolution of chronic disease in celiac patients who have been adhering faithfully to a long-term, gluten-free diet.

One thing that definitely associates with celiac disease is bone and tooth problems. Celiac patients often present with osteoporosis, osteopenia (thin bones), cavities or tooth enamel abnormalities (thanks Peter).

An Italian study showed that among 642 heart transplant candidates, 1.9% had anti-endomyosal antibodies (a feature of celiac), compared with 0.35% of controls. That's more than a 5-fold enrichment! The majority of those patients were presumably unaware of their celiac disease, so they were not eating a gluten-free diet.

Interestingly, celiac doesn't seem to cause obesity; to the contrary. That's one facet of modern health problems that it definitely does not cause.

The relationship between cancer and celiac disease is very interesting. The largest study I came across was conducted in Sweden using retrospective data from 12,000 celiac patients. They found that adult celiac patients have a higher overall risk of cancer, but that the extra risk disappears with age. The drop in cancer incidence may reflect dropping gluten following a celiac diagnosis. Here's another study showing that the elevated cancer risk occurs mostly in the first year after diagnosis, suggesting that eliminating gluten solves the problem. Interestingly, celiac patients have a greatly elevated risk of lymphoma, but a lower risk of breast cancer.

There's a very strong link between celiac and type I diabetes. In a large study, 1 in 8 type I diabetic children had celiac disease. This doesn't necessarily tell us much since celiac and type I diabetes are both autoimmune disorders.

One last study to add a nail to the coffin. Up to this point, all the studies I've mentioned have been purely observational, not able to establish a causal relationship. I came across a small study recently which examined the effect of a high-fiber diet on vitamin D metabolism in healthy (presumably non-celiac) adults. They broke the cohort up into two groups, and fed one group 20g of bran in addition to their normal diet. The other group got nothing extra. The bran-fed group had a vitamin D elimination half-life of 19.5 days, compared to 27.5 for the control group. In other words, for whatever reason, the group eating extra bran was burning through their vitamin D reserves 30% faster than the control group.

Unfortunately, the paper doesn't say what kind of bran it was, but it was probably wheat or oat (**Update- it's wheat bran**). This is important because it would determine if gluten was involved. Either way, it shows that something in grains can interfere with fat-soluble vitamin status, which is consistent with the staggering negative effect of refined wheat products on healthy non-industrialized cultures.

Add to this the possibility that many people may have some degree of gluten sensitivity, and you start to see a big problem. All together, the data are consistent with gluten grains interfering with fat-soluble vitamin status in a subset of people. As I discussed earlier, this could contribute to the diseases of civilization. These data don't prove anything conclusively, but I do find them thought-provoking.

Thanks to Dudua for the CC photo

Real Food VIII: Ghee

All this talk about butter is making me hungry. Richard mentioned in the comments that he bought some ghee recently and has been enjoying it, so I thought I'd post a recipe. Ghee is the Hindi word for clarified butter. It's butter that has had everything removed but the fat. Rich in fat-soluble vitamins and lacking the sometimes problematic lactose and casein, ghee has rightfully been considered a health food in India since ancient times.

Another advantage of ghee is its high smoke point, which is higher than butter because it doesn't contain any protein or sugars. Consequently, food sauteed in ghee has a clean, rich taste.

The recipe is simple but touchy. I recommend using the best butter you can get your hands on. 100% grass-fed, unsalted cultured butter is the best.

Ingredient and materials

• Butter (1 lb minimum)
• Wide-mouth glass jars
• Cheesecloth
• Rubber bands
  

Recipe

1. Place the butter in a saucepan and turn the heat to medium until it's melted.
   
2. Once it begins to boil, turn the heat down to low. It's very important to calibrate the heat correctly. Typically, you will want the burner on its lowest setting. The idea is to evaporate the water without burning the oil. It should boil, but slowly.
3. The melted butter starts out cloudy but gradually clears up as the water evaporates. At the same time, a crust will form on the surface of the ghee and the bottom of the pan. Keep the heat very low.
   
4. Push a portion of the top crust to the side with a spoon to see inside of the saucepan. When the butter looks clear and bubbles only rise from the bottom every few seconds, it's done. You have to be very careful because once the water has evaporated, the fat heats up quickly and burns the crust. This gives the ghee an acrid flavor and color. Make sure to handle the pot cautiously, because hot oil can give severe burns.
   
5. Allow the ghee to cool until it's warm but not hot. Place a piece of cheesecloth over the lid of your jar. Secure it with a rubber band. Pour the ghee through the cheesecloth, into the jar.
   
6. Store ghee in the refrigerator or at room temperature. It keeps much longer than butter.

The picture above is of my last batch of ghee.

Vitamin K2, menatetrenone (MK-4)

Weston Price established the importance of the MK-4 isoform of vitamin K2 (hereafter, K2) with a series of interesting experiments. He showed in chickens that blood levels of calcium and phosphorus depended both on vitamin A and K2, and that the two had synergistic effects on mineral absorption. He also showed that chickens preferred eating butter that was rich in K2 over butter low in K2, even when the investigators couldn't distinguish between them. Young turkeys fed K2-containing butter oil along with cod liver oil (A and D) also grew at a much faster rate than turkeys fed cod liver oil alone.

He hypothesized that vitamin A, vitamin D and vitamin K2 were synergistic and essential for proper growth and subsequent health. He particularly felt that the combination was important for proper mineral absorption and metabolism. He used a combination of high-vitamin cod liver oil and high-vitamin butter oil to heal cavities, reduce oral bacteria counts, and cure numerous other afflictions in his patients. He also showed that the healthy non-industrial groups he studied had a much higher intake of these fat-soluble, animal-derived vitamins than more modern cultures.

Price found an inverse correlation between the levels of K2 in butter and mortality from cardiovascular disease and pneumonia in a number of different regions. A recent study examined the relationship between K2 (MK-4 through 10) consumption and heart attack risk in 4,600 Dutch men. They found a strong inverse association between K2 consumption and heart attack mortality risk. Men with the highest K2 consumption had a whopping 51% lower risk of heart attack mortality and a 26% lower risk of death from all causes compared to men eating the least K2! Their sources of K2 MK-4 were eggs, meats and dairy. They obtained MK-5 through MK-10 from fermented foods and fish. The investigators found no association with K1, the form found in plants.

Perigord, France is the world's capital of foie gras, or fatty goose liver. Good news for the bon vivants: foie gras turns out to be the richest known source of K2. Perigord also has the lowest rate of cardiovascular mortality in France, a country already noted for its low CVD mortality.

Rats fed warfarin, a drug that inhibits K2 recycling, develop arterial calcification. Feeding the rats K2 completely inhibits this effect. Mice lacking matrix Gla protein (MGP), a vitamin K-dependent protein that guards against arterial calcification, develop heavily calcified aortas and die prematurely. So the link between K2 and cardiovascular disease is a very strong one.

Mammals can synthesize K2 MK-4 from K1 to some degree, so dietary K1 and other forms of vitamin K may contribute to K2 MK-4 status. 

The synergism Weston Price observed between vitamins A, D and K2 now has a solid mechanism. In a nutshell, vitamins A and D signal the production of some very important proteins, and K2 is required to activate them once they are made. Many of these proteins are involved in mineral metabolism, thus the effects Price saw in his experiments and observations in non-industrialized cultures. For example, osteocalcin is a protein that organizes calcium and phosphorus deposition in the bones and teeth. It's produced by cells in response to vitamins A and D, but requires K2 to perform its function. This suggests that the effects of vitamin D on bone health could be amplified greatly if it were administered along with K2. By itself, K2 is already highly protective against fractures in the elderly. It works out perfectly, since K2 also protects against vitamin D toxicity.

I'm not going to go through all the other data on K2 in detail, but suffice it to say it's very very important. I believe that K2 is a 'missing link' that explains many of our modern ills, just as Weston Price wrote. Here are a few more tidbits to whet your appetite: K2 may affect glucose control and insulin release (1, 2). It's concentrated in the brain, serving an as yet unknown function.

Hunter-gatherers didn't have multivitamins, they had nutrient-dense food. As long as you eat a natural diet containing some vegetables and some animal products, and lay off the processed grains, sugar and vegetable oil, the micronutrients will take care of themselves.

Vitamin K2, MK-4 is only found in animal products. The best sources known are grass-fed butter from cows eating rapidly growing grass, and foie gras. K2 tends to associate with beta-carotene in butter, so the darker the color, the more K2 it contains (also, the better it tastes). Fish eggs, other grass-fed dairy, shellfish, insects and other organ meats are also good sources. Chris Masterjohn compiled a list of food sources in his excellent article on the Weston Price foundation website. I highly recommend reading it if you want more detail. K2 MK-7 is found abundantly in natto, a type of fermented soybean, and it may be partially converted to MK-4.

Finally, you can also buy K2 supplements. The best one is butter oil, the very same stuff Price used to treat his patients. I have used this one personally, and I noticed positive effects on my skin overnight. Thorne research makes a synthetic liquid K2 MK-4 supplement that is easy to dose drop-wise to get natural amounts of it. Other K2 MK-4 supplements are much more concentrated than what you could get from food so I recommend avoiding them. I am generally against supplements, but I've ordered the Thorne product for a little self-experimentation. I want to see if it has the same effect on my skin as the butter oil (update- it does).

Activator X

Activator X, the almost-mythical vitamin discovered and characterized by Weston Price, has been identified! For those of you who are familiar with Weston Price's book 'Nutrition and Physical Degeneration', you know what I'm talking about. For the rest of you, allow me to explain.

Weston Price was a dentist and scientist in the early part of the 20th century. Practicing dentistry in Cleveland, he was amazed at the poor state of his patients' teeth and the suffering it inflicted. At the time, dental health was even worse than it is today, with some children in their teens already being fitted for dentures. Being a religious man, he could not bring himself to believe that 'physical degeneration' was what God intended for mankind. He traveled throughout the world looking for cultures that did not have crooked teeth or dental decay, and that also exhibited general health and well-being. And he found them. A lot of them.

These cultures were all considered 'primitive' at the time, and were not subject to the lifestyles or food choices of the Western world. He documented, numerically and with photographs, the near-absence of dental cavities and crooked teeth in a number of different cultures throughout the world. He showed that like all animals, humans are healthy and robust when occupying the right ecological niche. Price had a deep respect for the nutritional knowledge these cultures curated.

He also documented the result when these same cultures were exposed to Western diets of white flour, sugar and other industrially processed foods: they developed rampant cavities, their children grew with crooked teeth due to narrow dental arches, as well as a number of other strikingly familiar health problems. I think it's worth mentioning that Price's findings were universally corroborated by doctors in contact with the same cultures at the time. They are also corroborated by the archaeological record. Many of his findings were published in respected peer-reviewed journals. 'Nutrition and Physical Degeneration' is required reading for anyone interested in the relationship between nutrition and health.

Naturally, Price wanted to understand what healthy diets had in common besides the absence of white flour and sugar. Having studied cultures as diverse as the carnivorous Inuit, the dairy-eating Masai and agricultural groups in the Andes, he realized that humans are capable of thriving on very diverse foods. However, he did find one thing in common: they all ate some amount of fat-soluble, animal-derived vitamins. Even the near-vegetarian groups ate insects or small animals that were rich in these vitamins. He looked for, but did not find, a single group that was entirely vegetarian and had the teeth and health of the groups he described in 'Nutrition and Physical Degeneration'.

There were three vitamins he found abundantly in the diets of healthy non-industrialized people: A, D, and an unknown substance he called 'activator X'. He considered them all to be synergistic and critical for proper mineral metabolism (tooth and bone formation and maintenance) and general health. He had a chemical test for activator X, but he didn't know its chemical structure and so it remained unidentified. He found activator X most abundantly in grass-fed butter (but not grain fed!), organ meats, shellfish, insects, and fish eggs. Many of these foods were fed preferentially to pregnant or reproductive-age women in the groups he studied.

Price used extracts from grass-fed butter (activator X), in combination with high-vitamin cod liver oil (A and D), to prevent and reverse dental cavities in many of his patients. 'Nutrition and Physical Degeneration' contains X-rays of case studies showing re-calcification of severe cavities using this combination.

After reading his book, I wasn't sure what to make of activator X. If it's so important, why hasn't it been identified in the 60+ years since he described it? I'm happy to say, it finally has. In the summer of 2007, Chris Masterjohn wrote an article for the Weston Price foundation website, in which he identified Weston Price's mystery vitamin: it's vitamin K2, specifically the MK-4 isoform (menatetrenone).

It occurs exactly where Weston Price described it, and research is beginning to find that it's also critical for mineral metabolism, bone and tooth formation and maintenance. Its function is synergistic with vitamins A and D. To illustrate the point, where do A, D and K2 MK-4 all occur together in nature? Eggs and milk, the very foods that are designed to feed a growing animal. This is true from sea urchins to humans, confirming the ubiquitous and critical role of these nutrients. K2 has not yet been recognized as such by the mainstream, but it is every bit as important to health as A and D. The scientific cutting edge is beginning to catch on, however, due to some very tantalizing studies.

In the next post, I'll go into more detail about K2, what the science is telling us and where to get it.