10
May
2008

Metabolic Fingerprinting3

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fingerprint

Identification

Yes, it’s oh-so-middle-school, but we called it! Following the first ever metabolome-wide association study conducted across four countries, researchers are affirming the promise of metabolic fingerprinting in studying the links diet and other lifestyle factors have with specific disease risk. Once again, the focus is on gene expression, the resulting phenotype rather than our initial genetic “text.” Researchers compared levels of several metabolites (particles produced by the metabolic process) that were present in 4,630 subjects, who hailed from the U.S., the United Kingdom, China and Japan.

For the study, researchers took urine samples from volunteers aged between 40 and 59 and analysed these for over several thousand metabolite signals, using NMR spectroscopy and advanced statistics. The volunteers were participating in the INTERMAP study, an epidemiological study investigating the links between diet and blood pressure.

via Science Daily

The conclusions? Fingerprinting of subjects in the U.S. and U.K. indicated similar patterns, but these results substantially contrasted with patterns found in China or Japan. Differences were also significant between the profile results of Chinese and Japanese test subjects. To further confirm the lifestyle basis of these differences, researchers analyzed metabolite levels from Japanese and Japanese-American subjects. The comparative results indicated that Japanese-Americans’ metabolic profiles showed more similarity with other Americans’ metabolic patterns than they did with Japanese profiles. These metabolic patterns complement the difference in disease rates.

As Professor Paul Elliott, one of the study’s authors from the Department of Epidemiology and Public Health at Imperial College explains: “… whereas a person can’t alter their DNA, they can change their metabolic profile by changing their diet and lifestyle. This means that as we figure out where the problems lie, we should also be able to show people ways to reduce their risk of certain diseases.” Hmmm. Where have we heard that before?

This study further confirms our ongoing (and evolving) thesis that, from a genetic perspective, we’re very similar, at least when it comes to how we metabolize food and how our genes express themselves as a result of the foods we eat. Our genetic expression, for every single one of us, becomes the metabolic end product of our diet and lifestyle choices.

Given this study and its impact researchers hope it will have on personal disease risk assessment, you can go to a doctor and pay a lot of money to find out you have the metabolites that indicate a higher risk of certain diseases. (We pretty much know what the tests will show if you eat according to CW, right?) Or you can just concede that when you eat and live healthily (the Primal Blueprint way being our humble suggestion) your profile won’t take the shape of those insidious, high risk metabolic fingerprints.

Hmmm. We’d personally suggest saving yourself a few hundred or thousand bucks. We can think of better ways to unload that kind of cash – maybe a quarter grass-fed cattle order or a CSA share? A week-long trip to the mountains or beach, all in the name of stress relief?

Thoughts? Questions? Send ‘em on.

epadilla Flickr Photo (CC)

Further Reading:

Dear Mark: Gene Expression

Gene Expression: Location, Location, Location

Eye on DNA: Stunning Gene Expression Visualization

7
May
2008

Washboard Abs on a High-Fat Diet, No Ab Workouts and No Cardio?46

Mark Sisson

Me (54) in my backyard this morning

Apologies in advance for the self-serving nature of this post, but I felt that it was time to answer more specifically many of your questions about my own program and to use myself as an example of how the Primal Blueprint works if you integrate all the elements.

As many of you know, I am coming off a three month rehab from knee surgery. I’m about 95% healed now and can even do my “Indigenous Peoples Stretch” (a full unloaded squat) – a sure sign that all is well. Throughout this time, I have maintained my usual diet and have done whatever upper-body lifting I could manage that didn’t also require substantial leg involvement (pushups, pull-ups, dips, cable-work, etc). Despite my (or should I say “because of my”) high-fat diet and doing pretty much zero cardio over the past four months (including a fair amount of down time before the knee surgery) my weight, my lean mass and my body fat have all remained steady.

I went on FitDay.com a few days ago (great site to reveal the truth about what you eat) and entered what was a typical full day of eating for me. The results were pretty much as I expected: 2,458 calories, 58% of which was from fat; 165 grams of protein (1 gram per pound of body weight) and 114 grams of carbs. Now some might say that eating less than 2500 calories is too low for a moderately active man, but there are two points to make here. First, I am never really hungry. On this Primal Blueprint eating style, I eat when I want to and stop when I no longer feel hungry. Pretty simple. If I skip meals, I don’t get light-headed or famished. I don’t ever feel like I need more calories or that I am missing out on anything or “sacrificing” some guilty pleasure. I get plenty of protein to spare muscle and add to protein turnover. I get plenty of fat for fuel – sometimes 65% of daily calories. Second - and this goes to the heart of the Primal concept – when you eat fewer carbs, your body readily accesses dietary and stored fat for fuel. Even at 8% body fat, I still have 46,000 calories of stored fat, at least 25,000 of which is available to use as fuel at any time. Theoretically, you could walk 250 miles on that. It’s a beautiful thing when you direct gene expression to “want” to burn fat instead of always storing it. You certainly don’t need cardio to produce the full effect (you can if you want, within guidelines). As we often say here “80% of your results come from how you eat.” Conversely, eating more carbs drives up insulin, drives carbs towards fat storage, decreases fat-burning by prompting fat cells to hold on to stored fat and makes you hungrier for more carbs. I could burn some or most of all that off again by doing tons of cardio, but that only makes me hungrier for more carbs and perpetuates the cycle. It’s like digging a hole to put the ladder in to wash the basement windows.

The other point I want to make is that I don’t do abs. By that I mean I don’t specifically do an ab routine or ab classes as any part of my workouts. On the other hand, I pretty much work my abs all day long without specifically focusing on them. And that’s an important distinction. Grok probably had a wicked set of abs. He had to. Abs are the center of the human movement universe. They are part of today’s “core”, the fulcrum, the key in Chi. But you don’t necessarily need to do endless crunches, sit-ups, roman chairs, leg raises or other isolation moves to strengthen them. Sure, you can if you want, but I think the best way to work your abs is involve them in almost every other movement you do. Every time you do it. When you do pushups, you should tighten your abs hard, likewise when you do pull-ups, squats, lunges, curls - you name it. And working your abs doesn’t stop in the gym. When you sit at your desk, you should take that opportunity to tighten your abs (and by abs, we mean the whole complex: rectis and transverse abdominus, internal and external obliques, and pyrimidalis).

Tighten that belly as if you are going to be punched in the gut while blowing out the candles on your birthday cake. Hold it for 10, 20 or more seconds a few times every hour. Now do it while slightly tilted to one side. Now the other. For even better results and a stronger core, you would simultaneously contract your buttock muscles like you are trying to hold in the bean dinner you had at Barry’s last night. Do these short exercise bursts while you are driving to pick up the kids or when stuck in traffic. Hell, I do some of my best ab work bent over doing sprint work on the stationary bike. It’s really all about squeezing, tightening and trying to shorten the distance between your sternum and you pubic bone. This is all considered isometric work, but the abs respond extremely well to it. Eat right and those well-worked abs will show!

High-fat diet, no cardio, no ab workouts. Talk about thumbing your nose at Conventional Wisdom!

Further Reading:

What is the Primal Blueprint?

My Knee is Killing Me… No, Really.

My Daily Salad

Are There Any Good Carbs?

What I Eat in a Day

My Weekly Workout Routine

My Sprint Routine Video

Chronic Cardio

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29
April
2008

10 Ways to “Get Primal”26

Here at Mark’s Daily Apple, we advocate the Primal Blueprint Lifestyle, that is, a health philosophy that in large part acts to mimic the diet and physical activity of our pre-agricultural ancestors.

And, while we’ve explained in the past what it means to “Get Primal,” we figured what’s not to love about a bulleted list that reminds us how to incorporate these methods into our everyday lives.

Read on to learn how you can get primal on every level on every occasion:

Hike:

Whether it was searching for food, shelter or just greener pastures, our ancestors spent a lot of time taking the heel-toe express! (Though, it wasn’t exactly heel-toe in those days.) These days, of course, we have planes, trains and automobiles to get us from A to B, which means hoofing it has become our least likely mode of transport. To get back to the Primal Blueprint, set aside some time every week to participate in sustained activity as a way to return your body to its natural state (that is, being in a constant state of motion). And, although hiking was the primary modality for sustained exercise for our predecessors, feel free to substitute it for biking or any other low-level physical activity you can do for a long period with little interruption.

Sprint:

Although eat or be eaten is no longer really considered a threat in today’s society, for our ancestors, it was a pretty big (and potentially lethal) deal. The solution? Run fast, run hard, and run for your life! You can incorporate these same theories by adding a series of short sprints into your exercise routine (see Mark explain his sprint routine here). The idea here isn’t necessarily to be the fastest kid on the block (although that would be awesome), but rather to give all you’ve got for a brief period of time. Also, bear in mind that this concept of going hard and fast for a few seconds isn’t limited to the act of sprinting; you could try water sprints, power cycling, jump rope intervals or any other activity that requires short, intense bursts of energy.

Lift Hard:

Think Cavemen killed time pounding weights in a dingy gym? Think again! Our ancestors tested their strength only in real-life situations (as opposed to having a pose-off with the meathead in the cut-off shirt!) and grew strong by doing, for the most part, weight bearing exercises. Naturally, they focused on activities that would help them carry out real life functions. Want to work out like your primal ancestors? Try weight bearing activities such as squats or dead lifts, which our ancestors did when lifting a heavy rock or log for building; lunges, which mimic the action of transversing steep terrain or stepping into a throw; pull-ups and standing rows to mimic the movement of pulling a heavy object towards the body; pushing, to mimic the motion of… well, pushing things; and twisting motions such as medicine ball throws or cable woodchoppers, which our ancestors did when throwing spears or hoisting objects. For a new challenge (and an exercise that combines just about all of the above motions, try the Turkish get-up:

Ditch Grains and Sugar:

With the tagline “so simple even a caveman could do it,” the commercial suggests that our ancestors were, well, not the sharpest tools in the shed. But, clearly they were smart enough to shun grains and sugar (a feat that the majority of current day Americans have yet to accomplish). In fact, according to some anthropologists, our ancestors only consumed about 80 g of carbohydrates per day, largely because sources of carbohydrates – such as grains, beans and potatoes – are toxic in raw form. To keep it primal, avoid all grains, including bread, pasta, rice and noodles, and all refined sugar. It should also probably be noted that the majority (if not all) of processed foods are packed with carbs - either in the form of a grain, sugar, or both - so it’s best to cut those out too!

Eat Meat and Fish:

When dinner time rolled around for our ancestors, they weren’t exactly reaching for the yellow pages! Instead, they were reaching for a spear, ax or some other weapon to catch their meal. While we’re certainly not advocating that you begin hunting for your own entrees (people might talk!) we do recommend that you begin thinking about your diet in a way that resembles their dietary habits. That is, if you can’t catch it or find it in nature, you can’t eat it. In short, opt for meat and fish and don’t get hung up on the fat content. Not only is fat integral to health, it will also help keep you feeling satiated longer!

Eat Berries, Nuts and Unbridled Amounts of Veggies:

Again, when selecting foods, remember that you’re playing the role of the hunter and gatherer, so feel free to indulge in foods you would find in nature. Specifically, the Primal diet recommends berries, which are low in sugar and packed with vitamins, antioxidants and other beneficial nutrients, and nuts, including walnuts, brazil nuts, macadamias and almonds (but not peanuts which are a legume and should also be avoided for fear of aflatoxins). When it comes to vegetables, seek out root vegetables including carrots, turnips, parsnips, rutabagas and Swede (but not potatoes or other starchy, high-carb varieties), leafy greens, tomatoes and other brightly-hued vegetables (which not only add color to dishes, but also seriously improve the nutrition value).

Drink Water:

Although there is some back and forth about how much water our early ancestors actually consumed (with some anthropologists suggesting that early man got most of his water from the vegetables he consumed as opposed to risking his life standing in line with the other predators and prey at the local waterhole), the reality is that even if early man didn’t consume that much pure water, he certainly wasn’t reaching for a Coke. Get back to your primal roots by ditching the Gatorade, the soda (including the diet ones – they’re nearly as bad!) and especially the juice. All you really need is water, and lucky for you, it’s as easy as turning on the tap.

Sleep Smart:

When the sun went down, early man started prepping for bed. When the sun sets today, most men (and women) will do the dishes, watch Grey’s Anatomy, finish up paperwork, pay bills and check their email before falling asleep with the television blaring Conan O’Brien. No offense to Mr. O’Brien, but when nature starts heading to bed, so too should you. To catch Zzzs like our ancestors, remove all electronics from the bedroom and focus on creating an environment that is dark, quiet and serene. Also, while it might seem counterintuitive to not close the blinds, allowing natural light to be your wake-up call is far more refreshing (and natural) then waking to the shrills of an alarm clock.

Relax:

As much as we harp on about how hard early man had it (what with having to work hard to survive and all that), make no mistake, early man liked his downtime too! Unlike our ancestors, however, many of us tend to spend our downtime plunked in front of the TV or computer engaged(?) in mindless activity for hours on end. To get back to our primal roots, select an activity that will clear your mind and help you recharge and refocus. And don’t forget that part of this getting up and moving around a bit.

Crack a Coconut, Spear your Dinner and Sleep in a Cave:

Ok, maybe we’re kidding on this last one. But imagine how primal it’d make you feel!

mutbka, Jasmic, hrtmnstrfr, Bern@t, Genista, paurian, Snap, jahdakine, Mai, OnuRoca Flickr Photos (CC) and nightowl27 YouTube Clip

Further Reading:

My Knee is Killing Me… No Really.

Would Grok Chow the Cheese Plate?

What Mark Eats in a Day

28
April
2008

Dear Mark: Gene Expression10

Covering Your Bases

I received tons of emails from last week’s Gene Expression: Location, Location, Location post. Thanks to everybody for their feedback and questions. In the comment section of last week’s post, Ed was interested in other concrete examples of gene expression (the ability of a gene to produce a biologically active protein). In personal emails, others asked for more explanation of the difference between genes and gene expression. Still others wanted to hear more about the interaction between their gene expression and lifestyle choices. Given the range of reader questions this week, I thought I’d reframe this week’s Dear Mark to include more of an overview of this recurring MDA theme. There’s a lot to be said on the subject, and I promise this post won’t be the last word on it. Nonetheless, there’s no time like the present to give a proper introduction and dive right in.

Let me just say that gene expression is one of my favorite areas of interest, and it’s truly at the heart of the Primal Blueprint. In fact, it’s the real beauty of it as well. It confirms that the day-to-day choices we make have incredible impact. And we can influence gene expression to a far greater degree than anyone ever thought possible.

Everyone has the DNA “recipe” to build a human being. The DNA itself is not really so much a “blueprint” (as many people assume) as it is a recipe. As with all recipes, it allows for a little variation to spice things up and even room for improvement. That means that some ingredients can change a little and you still wind up with the intended result. A little more sugar, a little less salt, an added spice, a lower cooking temperature: the end result still resembles the picture in the cookbook.

We often hear about the computer hardware/software analogy. An analogy I like to use is that of a book and its readings. Your genome itself (your DNA) is fixed and can’t be changed. It is the book itself. Once it’s been written (and in this case each of your 60 trillion cells has the exact same copy of your story), you can’t change the words. But a book, even though it’s fixed, can be read differently by different people. (Imagine three different screenwriters taking the same book and coming up with three very different movie versions). The lines themselves are altered in the context of the interpretation.

Similarly, while your genes are “fixed”, the expression of those genes – the amount of proteins they cause to be made, whether or not they are even switched on or off at all – depends on the “environment,” the circumstances surrounding those genes. Diet, exercise, exposure to toxic chemicals (or fresh air), medicines, even the thoughts you think (which generate actual chemical signals) all influence gene expression – positively and/or negatively, depending on the choice. Eat a diet that is high in sugar, and gene expression moves in a direction that produces more insulin, that shuts off insulin receptors, that down-regulates lipase and other enzymes involved in fat-burning, that increases pro-inflammatory cytokines, etc. When you change to a diet low in sugars and rich in healthy fats, those or other genes are directed to reduce inflammatory expression, down-regulate insulin-producing metabolic machinery, up-regulate insulin receptors and rebuild cell membranes to reflect the presence of better building materials (omega 3 fatty acids, etc.). Research in gene expression is exploding right now and is examining both the impact of environmental factors and the promise of epigenetic therapies. The connection between insulin resistance and genetic expression (particularly in relation to exercise) was raised in last week’s comments. Diet and toxin exposure have been shown to influence gene expression in laboratory studies. Here are a few study abstracts to pique your interest: PubMed 1, 2, 3.

The interaction between lifestyle choices and gene expression goes on every second of every day you’re alive. You are literally rebuilding yourself all the time. That’s the message of hope that the Primal Blueprint offers. Even if you have so-called markers for “defective” genes, that doesn’t mean they will be expressed. Gene interaction is such that environmental factors can potentially allow for someone with BRCA1 and BRCA2 (associated with a very high risk for breast cancer) to never get breast cancer if those and related genes are properly controlled through environment. On the other hand, a woman with no risk factors can still get breast cancer if she directs gene expression towards pro-inflammatory pathways, then down-regulates other parts of her immune system.

As I mentioned last week, most of today’s genome investigation centers on SNPs (single nucleotide polymorphisms) that predispose the possessor to a particular condition (cancer, heart disease, obesity, diabetes, arthritis, etc). I’ve always said that a predisposition is not your final destiny. Even aging itself is highly influenced by gene expression over time. In the course of a lifetime, stem cells divide to repair injury (e.g. inflammation). In doing so, the cells are continually aged. The more the cells have to repair, the faster a person ages. This, of course, is a manifestation of gene expression.

The whole idea behind my Primal Blueprint is this: we know that we can influence gene expression, but – more than that – we know HOW to influence it in a direction of health, fitness, productivity, happiness, etc. The “blueprint” is not the DNA but a set of lifestyle and behavioral guidelines that, if followed, allows you to recast yourself as a healthy, fit person using “controlled gene expression”. The “primal” part comes from the recognition that our basic human DNA is relatively unchanged from the past 10,000 years. As long as we understand what it took to evolve to that point, we can find ways to continue to influence gene expression that are in alignment with that pre-agricultural DNA.

Thanks again for your comments and questions, and please keep them coming.

Dollar Bin, ott1mo Flickr Photos (CC)

Further Reading:

More Primal Blueprint posts

Gotta Love that Genome

24
April
2008

Gene Expression: Location, Location, Location10

Blue Genes

Geneticists at North Carolina State University have revealed an interesting lesson in gene expression: where you live can have significant impact on how your genes are expressed.

The scientists focused on a sample of 46 Moroccan Amazighs, a relatively homogenous group genetically-speaking. The subjects included desert nomads, mountain agrarians and coastal urban residents. The researchers analyzed the white blood cells of the group “to study the impact of the transition from traditional to urbanized lifestyles on the human immune system.” The results surprised even the scientists themselves: gene expression in the group varied by up to one-third based on geographic location and corresponding lifestyle.

They used the latest tools for characterizing the sequence and expression of all 23,000 human genes to compare the three Moroccan Amazigh groups. These groups were chosen because they have a similar genetic makeup but lead distinct ways of life and occupy different geographic domains. Thus, differences in gene expression profiles between the three groups would likely be due to environmental and not genetic factors. The team uncovered specific genes and pathways that are affected by lifestyle and geography. For example, they found respiratory genes were upregulated, or turned on, more frequently in the urban population than in the nomadic or agrarian populations.

via Science Daily

To confirm that differences were environmentally related, the scientists reviewed the genetic profile of random subjects in the three groups and found very little genetic variance. As they had expected, the significant difference in gene expression was initiated by environmental factors.

The differences they found in genetic expression logically fit with the environments’ corresponding challenges. The urban dwellers dealt with the city’s manufacturing-associated air pollution and higher level of viral pathogens on a daily basis. The upregulation observed in their respiratory genes, the scientists submit, is a response to the compromises present in their urban environment. And pollution was only one piece of the environmental picture and the impact of modern urban living. According to the scientists, the striking differences in gene expression were the likely result of a “combination” of lifestyle factors, including “nutrition, history of immune exposure, and psychological stress.”

This study, along with other research that examines the impact of environment on gene expression, affirms the message we try to offer on a regular basis: we are not at the mercy of our genes. How we play our genetic hand can matter as much as the cards we hold. Where we live, what we eat, what we’re exposed to and how we’re medically cared for, how active we are, and what levels of stress we deal with influence the expression of our genes. In keeping with this principle, the scientists who conducted the study offer this recommendation for future medical research and care:

Insight gained from this study highlights the impact transitions from traditional to modern lifestyles likely have on human disease susceptibility and further warrant the need to incorporate gene expression profiling alongside genetic association studies for the prediction of disease susceptibility.

Our modern lifestyles, as we say in the Primal Blueprint, create a deep chasm between our genetic expression and that of our ancestors. This study of populations in Morocco gives us a hint of that gap. It’s no coincidence that the Blueprint incorporates diet and physical activity similar to that of our primal history. (With good old Grok as our distinguished guide.) Likewise, the Primal Blueprint includes understanding and mitigating the damage created by the compromises of modern circumstance. Our bodies are remarkably adaptable, and genetic expression is evidence of this. However, this adaptability, constantly challenged and finally overstrained, cannot by itself compensate for the many modern burdens we impose. Our day to day choices matter, and knowledge is key.

Thoughts? Check back for more along the lines of lifestyle choices and gene expression in the future.

gabyigl, freckle m Flickr Photos (CC)

Further Reading:

More Primal Blueprint talk

Primal Blueprint Success Story

Nature Tops Nurture? Scientists Wrong Again…