Category Archives: Disease

The Case of the Killer Protein

Earlier this week a paper was released to much fanfare, claiming that diets with over 20% of energy as animal protein might be as life-threatening as smoking.

  • The Huffington Post said, “Atkins aficionados, Paleo enthusiasts, and Dukan devotees, you may want to reconsider what’s on your plate. While high-protein diets have been all the rage over the last few years for their waist-whittling goodness, a new study says they could be as bad for you as smoking.”
  • Scientific American said “People who eat a high-protein diet during middle age are more likely to die of cancer than those who eat less protein, a new study finds.”
  • NPR said, “Americans who ate a diet rich in animal protein during middle age were significantly more likely to die from cancer and other causes.” They added, “In an age when advocates of the Paleo Diet and other low-carb eating plans such as Atkins talk up the virtues of protein because of its satiating effects, expect plenty of people to be skeptical of the new findings.” A sound prognostication!

Ray, Alex, Navy87Guy, Kat, Sam, and others asked for my thoughts.

What the Researchers Did

The article appeared in Cell Metabolism, a high-impact journal which likes long complex papers reporting years of work. [1] A common strategy for getting into such journals is to piece together a great variety of work into one article, weaving a narrative theme to unite them. That’s what this article did, using the theme “high protein diets may shorten lifespan” to link several relatively disconnected projects.

The NHANES Findings

The work that generated most of the buzz was an analysis of data from the National Health and Nutrition Examination Survey (NHANES). They looked at a group of 6,381 NHANES respondents and found, “Respondents aged 50–65 reporting high protein intake had a 75% increase in overall mortality and a 4-fold increase in cancer death risk during the following 18 years. These associations were either abolished or attenuated if the proteins were plant derived.”

Here’s their Figure 1:

Longo et al Figure 1

Two oddities in this result raise red flags:

  • First, protein appears harmful at age 50, neutral at age 65, and beneficial at age 80. This reversal of effects is incompatible with most mechanisms by which protein could affect aging or disease risk. In animal studies, we see the opposite: protein restriction extends maximum lifespan, which means that at high ages, mortality is lower, but increases risk of early death, which means that in middle age mortality is higher.
  • Second, they report that the effect was specific to animal protein: “[W]hen the percent calories from animal protein was controlled for, the association between total protein and all-cause or cancer mortality was eliminated or significantly reduced, respectively, suggesting animal proteins are responsible for a significant portion of these relationships. When we controlled for the effect of plant-based protein, there was no change in the association between protein intake and mortality, indicating that high levels of animal proteins promote mortality.” Yet, plant and animal proteins are biologically similar.

These two oddities strongly suggest that the appearance of negative health outcomes from protein is due to confounding factors – behaviors or foods associated with animal protein consumption in middle age, rather than effects caused by the protein itself.

When we look at how the analysis was performed, we find more reasons to doubt that protein is at fault. All of this data was found using a model which adjusted for the following covariates:

Model 1 (baseline model): Adjusted for age, sex, race/ethnicity, education, waist circumference, smoking, chronic conditions (diabetes, cancer, myocardial infarction), trying to lose weight in the last year, diet changed in the last year, reported intake representative of typical diet, and total calories.

Adjustment for a host of health-related conditions – waist circumference, diabetes, cancer, myocardian infarction, and even total calories which is effectively a proxy for obesity – can radically distort results, and even transform effects from positive to negative. I’ve discussed this issue previously in The Case of the Killer Vitamins.

In practice, many factors are highly correlated. The variables being studied – protein intake, waist circumference, total calorie intake, and others – are beset by the problem of collinearity. Attempting multiple regression analysis on collinear variables can generate very peculiar results. The more the number of adjustment factors grows, the more strange things tend to happen to data.

If they wanted us to understand whether their results are trustworthy, authors would present raw data, and then a sensitivity analysis that shows how introducing each covariate individually affects the results, then showing how including combinations of two covariates affects the results, and so forth. This would help us judge how robust the results are to alternative methods of analysis.

Of course, authors do not do this. Instead, they ask us to trust the analysis they have chosen to present – which is only one of billions they could have done. (This study adjusted for 13 covariates. The NHANES survey may have gathered data on, say, 40 variables. There are 40 choose 13, or 12 billion, possible multivariate regression analyses that could be performed using 13 covariates on this data set. Each of the 12 billion analyses would generate different outcomes.)

Are the authors trustworthy? Unfortunately, most academics today are not. Career and funding pressures are severe, and by and large those who are good at gaming the funding and publishing processes have triumphed professionally over careful, diligent truth seekers. It is much easier to construct a narrative that will garner attention and publicity and interest, than to carefully exclude non-robust results and publish only those results that are solidly supported.

Frankly, I give little credence to their NHANES analysis. And, judging by comments in the press, other epidemiologists don’t seem to give it much credence either. From the NPR article:

But could eating meat and cheese really be as bad for you as smoking, as the university news release describing the new Cell Metabolism paper suggested?

Well, that may be an exaggeration, according to Dr. Frank Hu, a researcher at the Harvard School of Public Health who studies the links between health, diet and lifestyle.

“The harmful effects of smoking on cancer and mortality are well-established to be substantial, while the harmful effects of red meat consumption are modest in comparison,” Hu wrote to us in an email.

The Mouse Experiments

So let’s turn to the next part of the study, the mouse experiments:

Eighteen-week-old male C57BL/6 mice were fed continuously for 39 days with experimental, isocaloric diets designed to provide either a high (18%) or a low (4%–7%) amount of calories derived from protein …

The low protein diets are really starvation diets, in terms of protein intake. The reason the low protein diets were sometimes 4% and sometimes 7% was because mice will often lose weight on 4% protein diets due to starvation (in the paper’s experiments on BALB/c mice, “the mice had to be switched from a 4% to a 7% kcal from protein diet within the first week in order to prevent weight loss.”). Animal control officers do not allow experiments to continue if the mice are obviously starving.

[B]oth groups were implanted subcutaneously with 20,000 syngeneic murine melanoma cells (B16).

This is an unusually small number of cells. Typically, cancer researchers implant a million cells to create a syngeneic tumor. Presumably they used this small number of cells in order to ensure that some mice would not develop tumors during the 39 day experiment. As it happened, this was a lucky (canny?) choice of cell quantity: while 10 of 10 mice on the high-protein diet developed tumors during the experiment, only 9 of 10 mice on the low-protein diet did. If they had used more cells, all mice on both diets would have developed tumors; if they had used fewer cells, some mice on the high protein diet would have failed to develop tumors. Either way, the results would appear less damning for the high protein diet.

The outcomes:

Longo et al Figure 3
Due to the small number of cells injected, it takes at least two weeks before tumors are detectable in size (normally they would be visible in ten days). They seem to be similar in size at about two weeks after implantation.

However, when the tumors reach larger sizes, growth is impaired on the low protein diets. A mouse weighs 20 grams, and a 2000 mm3 tumor weighs 2 grams, or 10% of body weight – equivalent to a 15-pound tumor in humans. Growing a tumor of this size requires building a large amount of tissue — blood vessels, extracellular matrix, and more. The ability to construct new tissue is constrained on a protein-starved diet, so it’s not surprising that tumor growth is slower when the tumor is large and protein is severely restricted.

Animal protocols generally require that mice be sacrificed when tumors reach 2000 mm3. Extrapolating the tumor growth curves, it looks like the mice in experiment (B) would be sacrificed 5 weeks after implantation on the high protein diet, or 8 weeks after implantation on the low protein diet; in experiment (G), mice on the high protein diet would be sacrificed about 9 weeks after implantation, while mice on low protein diets would have been sacrificed about 11 weeks after implantation.

In other words, tumors still kill you, just a bit more slowly if you are starving yourself.

It’s important to note a couple of things. First, the word “starving” is appropriate. 4% to 7% protein intakes are starvation levels for mice. In a nice blog post closely relevant to this topic, Chris Masterjohn notes that a 5% protein intake completely stunts the growth of young rats:

Chris rhetorically asks: “How many of us would deliberately feed a two-year old a diet that would cause them to stop growing altogether?”

Second, as Chris also points out in the same post, such low protein intakes actually make cancer more likely in the context of exposure to mutagens. For instance, aflatoxin exposure leads to cancer (or pre-cancerous neoplasms) much more frequently in rats on low-protein diets than in rats on high-protein diets:

In this experiment, there were two diets, 5% protein and 20% protein, and two diet periods, one during exposure to aflatoxin and one afterward. Rats exposed to aflatoxin while on a 5% protein diet were far more likely to develop neoplasms than rats exposed to aflatoxin on a higher protein diet. That is, the “20-5” rats had far fewer cancers than the “5-5” rats, and the “20-20” rats had far fewer cancers than the “5-20” rats. High protein for the win!

However, once the rats had neoplasms, the tumors grew more slowly on the low-protein diet. Just as the new study found.

So, if your goal is to avoid getting cancer, it is better to eat adequate protein. If you already have cancer, or if researchers have injected you with highly metastatic melanoma cells, you can buy yourself slightly slower tumor growth by starving yourself of protein. In laboratory mice, this extends lifespan a few weeks because they are not allowed to die from cancer, but are sacrificed when tumors reach a specific size. In humans, however, cancer death commonly follows from cachexia, or wasting of lean tissue. A low protein diet might promote cachexia and accelerate cancer death in humans. It is not possible to infer from this study that there would be a clinical benefit to a low protein diet in human cancer patients.

Other Negative Effects of Low-Protein Diets

The study noted a significant negative effect of low protein diets in older mice. While young mice (18 weeks, equivalent to young adults) lost only a few percent of body weight on the starvation low protein diets, elderly mice (2 years old) wasted away on low protein diets. The data:

Longo et al Figure 4

Both young and old mice managed to gain a bit of weight on the high protein diets, and both young and old mice lost weight on the low protein diets. The weight loss was much more severe in elderly than young mice.

Considering that wasting away commonly precedes death in the elderly, this is not a good sign for the low protein diets. The authors themselves argue that this is consistent with the NHANES finding that high protein diets become beneficial after age 65: “old but not young mice on a low protein diet lost 10% of their weight by day 15, in agreement with the effect of aging on turning the beneficial effects of protein restriction on mortality into negative effects.”

However, while I think it is clear that the dramatic weight loss in the elderly mice fed low protein is harmful, it is far from clear that the slight weight loss of the younger mice was harmless. Though they maintained their weight better than elderly mice, they may have been starving as well. To actually support the NHANES survey, the researchers should have maintained the mice on low or high protein diets for several years, and seen which group lived longer. They did not do this.

If they had, I speculate that the high protein mice would have lived longer.

Conclusion

This is a study in the line of T. Colin Campbell and other vegetarians who have tried to show that animal protein promotes cancer and mortality. These studies are unconvincing. They simply do not prove the conclusions they purport to draw.

The Perfect Health Diet takes a middle ground in regard to protein: We recommend eating about 15% protein, and argue that both high protein and low protein diets are likely to be harmful; high protein diets by accelerating aging or by making protein available to gut bacteria for fermentation, producing a less beneficial gut flora and generating nitrogenous toxins; low protein diets by starving the body of a key nutrient needed to maintain bodily functions, especially liver, kidney, and immune function.

Nothing in this study persuades me that those recommendations need revision.

References

[1] Levine ME et al. Low Protein Intake Is Associated with a Major Reduction in IGF-1, Cancer, and Overall Mortality in the 65 and Younger but Not Older Population. Cell Metabolism 19, 407–417, March 4, 2014. http://www.cell.com/cell-metabolism/retrieve/pii/S155041311400062X.

Curing Ankylosing Spondylitis

Ankylosing spondylitis is a fearsome disease. The Mayo Clinic states:

Ankylosing spondylitis is an inflammatory disease that can cause some of the vertebrae in your spine to fuse together. This fusing makes the spine less flexible and can result in a hunched-forward posture. A severe case of ankylosing spondylitis can make it impossible for you to lift your head high enough to see forward….

Inflammation also can occur in other parts of your body — such as your eyes and bowels.

There is no cure for ankylosing spondylitis, but treatments can decrease your pain and lessen your symptoms.

But the “no cure” part is probably mistaken. Yesterday I received an email from Steven Morgan:

Hey Paul,

Your website and book saved my ass and gave me a chance to recover from Ankylosing Spondylitis, no small feat.  I made a video about it here:  http://www.youtube.com/watch?v=qvgjJTLrM3M

There was a thread on your site about high cholesterol and possible causes when going Paleo.  That thread was HUGE in my recovery….  My cholesterol fell over 200 points in two months!

Anyhow, you’re the best.  Thank you!

Cheers,

Steven

Here’s Steven’s story:

In a follow-up email, Steven elaborated:

My health is fantastic lately!  I’m still able to push the edges of what I can tolerate, and am enjoying eating butter, some white-rice based gluten-free breads, some vegetables, and occasionally cheddar cheese.  Sure beats just the 5 foods I took on my trip!  Well, to be honest, after several months of just eating coconut, cacao, pemmican, fish, and white rice, I grew quite fond of it all.  It’s amazing how your palate can change.

I gave Steven a few suggestions that I think would help anyone with AS:

  • Nutrition:
    • Vitamin A (1/4 to 1/3 lb liver per week plus spinach, sweet potatoes, yams, carrots, persimmons)
    • Vitamin D from sun and supplements.
    • Vitamin C
    • Collagen from soups and stews with joints, bones, tendons, and tripe.
    • Zinc and iodine.
  • Circadian rhythm entrainment
  • Intermittent fasting

Steven wants to share experiences with other ankylosing spondylitis sufferers; he asked me to “let folks know I’d be happy to connect; I’m especially interested in connecting with other people who have AS!” You can reach Steven by email at stevenmorganjr@gmail.com.

Conclusion

The Mayo Clinic is correct that medicine offers no cure for ankylosing spondylitis; but diet and lifestyle may do better. AS is probably an infectious condition caused by a pathogenic gut flora. Improved immune function and remodeling of the gut microbiome ought to be able to work a cure.

Steven experimented with a no-starch diet, but had better results on something more PHD like. As we’ve discussed, eating carbs is important for formation of the intestinal mucosal barrier and for proper immune function. A very low-carb diet often delivers short-term relief by starving pathogens, but it doesn’t support a probiotic gut flora and can bring long-term problems from suppressed immunity and impaired gut barrier integrity. That often leads to food sensitivities like those Steven suffered from. It’s better to obtain sufficient dietary carbohydrates to support a healthy gut. White rice is often one of the easier carbs to start with.

Thanks for writing, Steven! Your experiences and video should give hope to AS sufferers everywhere!

Autoimmune Panel: Wahls, Ballantyne, Jaminet, & Gray

This is probably the most important and interesting podcast I’ve had the privilege of being part of: an expert panel on Recovering from Autoimmune and Neurodegenerative Diseases.

The panel was arranged by Whitney Ross Gray of Nutrisclerosis, who has recovered from Multiple Sclerosis with an ancestral diet rich in animal foods.

The expert panelists were:

  • Terry Wahls, M.D., who has famously recovered from Multiple Sclerosis on an ancestral diet rich in plant foods, and is now leading a clinical trial studying ancestral diets as treatments for M.S.
  • Sarah Ballantyne, Ph.D., who blogs at The Paleo Mom. Sarah suffered from an autoimmune disease, lichen planus, as well as other ailments, and healed them (and lost 120 pounds) with an ancestral diet.
  • Paul Jaminet, Ph.D. I had a chronic disease with neurological symptoms that overlapped with M.S., but it turned out to be an infectious disease and cleared with antibiotics. However, this could not be diagnosed until after I’d made considerable progress addressing it through an ancestral diet, which became the Perfect Health Diet.

Questions were solicited beforehand from patients suffering from autoimmune and neurodegenerative diseases, and in an hour and forty minutes we covered many fascinating topics.

I think the combination of personal experience recovering from chronic diseases, and scientific and medical expertise, made for an exceptionally useful conversation. If you are interested in these diseases – or just in how to be healthy, since the methods that address these conditions are generally beneficial for anyone’s health – take a listen.

My thanks to Whitney for organizing the discussion, Carl for hosting it, and Terry and Sarah for making a great panel.

Circus, Swim, and Nails: Three Cancer Stories

Last weekend we want to see Cavalia Odysséo, a circus of horses, acrobats, and aerialists. It is a magnificent show.

Our trip to the circus began, in a way, many months ago. In March 2012, I got an email that began, “My mother has terminal cancer.”

PHD and Laurette Charron’s Cancer

The email was from Michel Charron, an aerialist with Cavalia Odysséo. Here is what he wrote:

I rushed home from Miami … to New Brunswick, Canada, to see what I could do for Mom.  The doctors say there is nothing they can do for her now….  The doctors have already decided that she is dead, and that there is nothing to be done but to keep her as comfortable as possible to the end.

She has cancer of the liver and of the colon.  They have found lesions on her lungs, which they believe are also cancerous….

When I arrived ten days ago, my mother was totally unrecognizable.  She was taking six pain pills a day, had no tone in her facial expressions, could not pronounce the letter ‘s’ properly, had severely restricted mobility, as well as difficulty concentrating and following regular conversation….

We are all alone here and would greatly appreciate some friendly advice.

I gave my cancer suggestions. The gist of my dietary advice for cancer can be found in these two posts: An Anti-Cancer Diet, September 28, 2011, and Toward an Anti-Cancer Diet, September 15, 2011. Extracellular matrix is very important, so soups and stews with connective tissue are important. Good, balanced nutrition is crucial; many nutrient deficiencies, excesses, and imbalances promote cancer. Lifestyle is very important too: circadian rhythm entrainment may be the single most important factor determining cancer prognosis.

I didn’t hear from Michel for seventeen months. Last Friday, Michel sent another email:

I contacted you last year regarding my mother, Laurette, who was diagnosed with generalized cancer and given very little time to live.  You proved a light in very, very dark times.  My mother not only lived nine months longer than predicted, but the quality of her life improved dramatically.  Thank you for that.

Cancer is a terrible disease, and had Laurette’s cancer been caught earlier there would have been hope of recovery, but Michel was grateful for the extra time he had with his mom. She got off most of her prescription medications, dropping from 22 drugs to 5, and became physically and mentally able to enjoy what remained of her life. Michel and Laurette were able to spend time together, share their love for each other, and say farewell.

It happens that Cavalia Odysséo is playing in Boston right now, and Michel invited us to the show. If you ever have a chance, it is well worth a trip. The horses – there are 63 horses in the show – are a pleasure to watch; the scenery is magnificent; and the performers superb. This trailer will give you an idea of the show:

Here is the circus tent:

cavalia 01

Michel invited us back stage after the show. Here we are with some of the performers – Michel is holding our book:

cavalia 03

With Michel and his wife and co-performer Tomoko:

cavalia 03b

Some of the horses, exhausted by the show, turn their backs to visitors:

cavalia 02

And here I am getting a lesson in aerialism from Michel:

cavalia 04

Thank you, Michel! It was a magical night.

The Big Swim

If you’ve read the jacket of our book, you’ll know that Court Wing, head trainer at CrossFit NYC, says in his blurb, “One of my best friends was on the diet while undergoing chemo and his bloodwork numbers were so good that they would have been considered average … for a person without cancer.”

I haven’t yet told the story of Court’s friend, D. Kirk MacLeod. Kirk discovered he had cancer when his colon ruptured in August 2010. He’s had multiple surgeries and chemotherapies since.

Kirk has now done something remarkable. On August 4, he swam the Northumberland Strait between New Brunswick and Prince Edward Island – an 11 mile swim. He wrote beforehand:

I really do feel like I am accomplishing the impossible… I have gone from less than 160 pounds, weak and worn from chemotherapy before Christmas (less than I weighed in high school!) and two major surgeries in February and March…to 185 pounds, fit, strong and ready to swim over 14 kilometres on Sunday, August 4th!!! I started slowly training at the beginning of June!

In July I started training “hard” under the guidance of Court Wing (my Crossfit coach from Crossfit NYC) and Max Wunderle (my swim coach of TriMax Fitness). I also had invaluable eating advice from Paul Jaminet (The Perfect Health Diet). Their help and direction has been phenomenal – I couldn’t have done it without them!

After the swim, Kirk wrote:

It was brilliant… It was hard as hell…and it was an accomplishment I never imagined….

I finished in 6 hours and 25 minutes. We figure I swam about 17 km … maybe more.

I was only cleared to train at the end of May and started training in June…I began at zero. I couldn’t even do basic exercises with weights. I wasn’t a swimmer. I had never trained in swimming.

It’s an incredible story and an incredible accomplishment. Here’s Kirk:

cavalia 05

Kirk did his “Big Swim” to benefit the Brigadoon Children’s Camp Society, a charity for chronically ill kids. If you’d like to reward his hard work, donate here through Canada Helps.

Cancer and Nailbiting

Reports from other cancer patients suggest that cancer therapies are much less toxic when patients are eating PHD. Here, for example, is Bill Rafter:

About 6 months ago I learned that I had metastatic prostate cancer. The treatment recommended was hormone therapy and targeted radiation…. The effects are a total suppression of sexual drive, hot flashes similar to those experienced by menopausal women, and the feeling that one is an old, old man…. I found the last one particularly brutal, and questioned whether I wanted treatment at all.

A friend gave me a good book on cancer, recommending an all-out approach rather than the sequential attempts favored by most oncologists. Nutrition was a major part of the approach. I then trolled my friends for books on nutrition and one commented that PHD was the best he had ever read. I am overwhelmed by what it has done for me.

After reading PHD, I immediately adopted the recommendations in full, with the exception of fasting. I then went thru 44 radiation treatments, and never felt fatigue, a common symptom. No more old man feelings, and no thoughts of quitting treatment. Hot flashes are completely gone, which really puzzles the oncologists. Everyone wants to know what stopped the hot flashes.

Of course breezing through therapy is not the same as recovering, but it is a good start. If therapies have fewer side effects, higher doses can be utilized, and treatments might be more effective.

Bill continued:

But that’s not all. Ever since grade school I have been a nailbiter. I knew the habit was caused by a chemical imbalance, rather than behavioral, but could never figure out what. But since adopting PHD, my fingernails have grown to the extent that filing them is annoying. That makes me wonder that if PHD brought my system into balance, how many other imbalanced people could also benefit.

I think a lot of people can benefit from PHD. Similar to Bill’s case, it’s rare for only one health condition to improve when diet and lifestyle are improved. Usually all or nearly all health problems improve. This suggests that poor diet and lifestyle are contributors to many diseases.

Invitation to Perfect Health Retreats

A few recent events have increased my interest in how PHD, or ancestral diet and lifestyle generally, affect cancer:

  • Shou-Ching and I have recently been asked to assist in developing the dietary and lifestyle advice for a cancer clinical trial.
  • Our Perfect Health Retreats provide a fairly controlled environment where we might be able to see and measure the effect of PHD on cancer patients. Michel told us that when he put his mother on PHD, he saw notable improvements after two weeks. So a thirty day program may be long enough to generate observable results.
  • The launch of the Journal of Evolution and Health gives a scholarly forum for communicating observations and exploring hypotheses.

As readers know, my mother died of cancer, so this is of special interest to me. I suspect that diet and lifestyle have a much bigger impact on cancer than most realize. There is shockingly little research underway into this aspect of cancer management.

To gain more insight into how diet and lifestyle may affect cancer outcomes, I’d like to invite cancer patients to come to our Perfect Health Retreats. Perfect Health Retreats are not a medical program, there is no medical treatment or advice available – just great food, an environment designed for optimal healthfulness, and an educational program teaching how to live for optimal health. So the program will not be suitable for severely ill patients.

If you’re interested in participating, please contact me at 617-576-1753 or paul@perfecthealthretreat.com, or Whitney Ross Gray at 910-763-8530 or whitney@perfecthealthretreat.com.

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