Yes, I know A New Hope was episode 4, but I could not think of a catchy but Germaine line that sounds like “Revenge of The Sith”, and this thing was only supposed to be two parts as it is! Call it artistic license I guess.

If you missed part 1 and part 2 make sure to check those out.

I want to look at some of the specific claims, misconceptions, and actual benefits surrounding low carb. I think I’ve said this a few times now, but I’ll make the point again: I see many important uses for LC/ketogenic diets. I had more than a few comment that Keto was the “only” way they could control their autoimmune condition. Bully for them, and this is precisely why we need to not only research LC, but be willing to pull it out of the tool box and give it a whirl. While we are doing that though, let’s remember we have other tools, and situations in which LC simply is not going to be appropriate. No need to get poopy pants over all that, better to just learn and grow.

Is ketosis the “natural” state for humans?

I must throw myself under the bus on this one. I do not think it’d be tough to do some google searching and find some circa 2003-2004 era comments on my part stating ketosis was THE natural metabolic state for humans. I based this off the observation that ketosis was effective for a host of ills and might hold some promise for an extended lifespan (I’ll get to that mistake in a bit). Something I had not considered in all this was that the efficacy of ketosis had nothing to do with it being the natural metabolic state for humans, and everything to do with limiting the ingestion of too many calories and reducing pro-inflammatory gut irritants. When I started looking at the animal models of ketosis, it was interesting that we were not seeing therapeutic benefit of ketosis Vs. the animals natural diet, but rather a protective effect of not feeding critters diets that were KNOWN to cause metabolic problems. I talked at length about that in my post “Of Mice and Morons.” Said another way: We do not see metabolic problems in free-living animals such as mice, nor do we see these issues in contemporarily studied hunter gatherers. And, with the exception of the Inuit, none of these humans or critters are consistently in ketosis.

That LC can be used as a powerful therapeutic tool is without a doubt, but it has tricked more than just me into mistaking the effect of a therapeutic intervention for a cause. For more than 100 years medical practitioners recommended a LC approach for weight loss, but for the reasons related to specific individual insulin resistance AND satiety. Some folks do well on higher carb, some better on lower. We can do theory and internet flame wars all day and never get to a point that helps people. Or, we can take general guidelines, encourage folks to tinker, and actually see some results for our efforts.

One of the best explanations I have seen to date on both the important role of dietary carbohydrate in human health, and a credible mechanistic explanation of the pathogenesis of insulin resistance, is encapsulated in Chris Masterjohn’s talk at AHS 2012. I have seen similar proposed mechanisms of insulin resistance and fat gain being an adaptation to reduce oxidative stress since perhaps 2008, but Chris nails this.

Please watch the entire video and ponder upon it’s implications a bit, especially if you are leaning towards the Insulin hypothesis crowd.

Chris Masterjohn — Oxidative Stress & Carbohydrate Intolerance: An Ancestral Perspective from Ancestral Health Society on Vimeo.

We have a mechanism whereby excess calories can be either pushed through the mitochondria, causing severe oxidative stress, or we have fat gain and insulin resistance occurring in an effort to “lock up” excess calories and glucose, which can both pose significant metabolic problems. Let me say this again, as it’s important that folks get this: Insulin resistance is likely an effort to prevent cellular death due to free-radical production. This is facilitated by pushing substrates (primarily fat and carbs) into adipose tissue, which is RELATIVELY inert (aside from the hormonal messengers that adipose tissue produces). We also see elevated lipoproteins, triglycerides, and blood glucose as the body is trying to put nutrients ANYWHERE other than through the mitochondria. I’m working on a future post that will look at instances of insulin resistance not related to a caloric excess. What we see is another example of the body responding to stress. Stay tuned for that.

We can actually see a nice pharmaceutically induced version of this mitochondrial substrate overload from the drug 2.4-dinitrophenol (DNP). DNP causes uncoupling proteins to essentially “leak” electrons/protons out of the electron transport system. The effect is a lot of heat, and a lot of waste. The electron transport chain is designed to create a potential energy cascade to be utilized to build molecules like ATP and it’s intermediaries. If we are cold, we see these uncoupling proteins become more active in an attempt to boost our temperature. If we are eating an antioxidant rich paleo diet, not too much to worry about in all this. If we are nutrient deficient, this can be problematic due to the reactive oxygen species (ROS) which damage everything from proteins to organelles to DNA. This is what we see in the case of DNP, as many people have died from using the drug due to multiple organ failures as a result of ROS overwhelming the bodies ability to buffer this oxidative activity. An individual who overeats tends to be ‘warm.” This is a mild level of uncoupling protein activity attempting to “burn off” the excess cals. The body knows that too much of this will kill it immediately, so substrates are pushed into adipose tissue where it will kill one a bit more slowly.

That was a bit of an important side-road, let’s get back to Chris’ talk: This adaptation to excess calories fits the data much better than the insulin hypothesis, but again, does not diminish the therapeutic benefit of LC for specific populations. In his talk, Chris also discusses the gene frequency of amylase in both humans and primates. Even the least “carb adapted” humans have several more copies of the amylase gene than do chimpanzees, which implies a significant selection pressure to both maintain and propagate this selective advantage. Amylase is the enzyme used to digest STARCH.

If you follow the work of Richard Wrangham, you will understand that cooking is an important feature in all this, as amylase activity is best on starch which has been gelatinized via cooking. You can wrap the Expensive Tissue hypothesis right into this…humans started cooking both meat and starch, gut got smaller, brains got bigger. We appear to have strongly selected for the genes to assist in starch digestion. This wraps back around to the question of whether or not ketosis is the default metabolic state for humans. It seems a stretch when you consider the significant genetic and digestive machinery that has been allocated to dealing with starch. What I found particularly interesting in the talk is that we do not only see improved starch digestion with increasing numbers of these genes, but a lock-step improvement in insulin signaling Those people with the best ability to digest starch also have the best ability to handle the associated glycemic load.

One final point in this line: ketosis is the metabolic state of starvation OR significant carbohydrate restriction+ moderate to low protein intake. There are many good primers on the specifics of ketosis, including specific substrates produced, as well as the protein sparing effects of ketosis during starvation. I’m not going to reinvent the wheel on that, so if you want some specifics on ketosis, exercise your Google-Fu. What is intriguing to me is that if one consumes just a few too many carbs, or protein, one is bounced OUT of ketosis. I could easily imagine a system in which excess carbs or protein would be shuttled to storage activities, leaving ketosis humming along…as the “natural metabolic state.” Interestingly however, we see the exact opposite, the body seems to leap out of ketosis at any opportunity. I’d wager the default metabolic state is actually one of “metabolic plasticity.” We see pathology when folks can metabolize limited amounts of any of the macronutrients, with associated pathology and decreased health and longevity. Diabetes is a prime example in which folks lose the ability to properly handle carbs. One of my all time favorite papers, Secrets of the Lac-Operon describes exactly this. Aging cells are those which lose the ability to use fat as a fuel source due to mitochondrial damage. INTERESTINGLY however, transient carb exposure (cyclic low carb?) seems to offer both the metabolic flexibility of maintaining mitochondrial fat utilization, but also the hormetic stress response associated with transient elevated glucose levels. What this means in practical terms is cells show a more youthful profile while we also have systemic mechanisms which help to reduce the advanced glycation end products (AGE’s) which are inevitable with circulating blood glucose. If you are a fan of Art Devany, fractals, and punctuated equilibrium, this is in that wheelhouse.

Sorry about the diversion into uncoupling proteins, it just seemed to “fit” there. Hopefully this gave you some gristle to chew on regarding the claim that ketosis is the “natural” state for humans. The “natural” state for healthy humans is clearly not a static location but is typified by metabolic plasticity. We see pathology at those margins where ANY substrate starts creating problems. We see this in a host of genetic diseases, like various fatty acid metabolism diseases in which certain chain length fats cannot be metabolized (and can build up and kill the person). We see this with amino acid metabolism issues in the form of phenylketonuria (PKU) (the amino acid phenylalanine is not well metabolized, and can again, build up in the system and cause problems). We also see this in garden variety diabetes in which blood glucose is not easily disposed, and can subsequently wreak havoc via advanced glycation end-products. This fuel-storage/excess model is compelling to me due to the mechanistic robustness…it’s just kind of bad ass, but it also offers up an evolutionary survival story in that this process has been conserved due to it’s survival potential. Something I’m going to do is look at the proposed evolutionary advantage of various metabolic diseases such as PKU. It might be interesting to know WHY these diseases have stuck with the population.

What about longevity?

I was likely one of the most vocal advocates of LC for anti-aging purposes, and I do think the concept has merit…but within constraints. I know intermittent fasting is quite popular these days. I do not toot my own horn too often, but I’ll take credit for a big chunk of that, as I wrote about it back in 2005, and had been talking about it on the CrossFit message board as early as 2003. Studies, looking at mice to fruit flies to macaques, seemed to indicate ketosis, as associated with calorie restriction or intermittent fasting, could dramatically extend life. The data on the short-lived critters was crystal clear: one could expect an almost doubling of average lifespan from intermittent fasting or CRAN (calorie restriction adequate nutrition). Early work in primates looked promising. I thought we had a method that might dramatically improve health and lifespan. Well, unfortunately, humans are not fruit fly’s, nor rodents. In humans the genetic reaction norms are such that we do not allocate significant amounts of energy rearing our young RELATIVE to many other species.

This is a long but outstanding piece on genetic reaction norms. If you want to comment on the POTENTIAL of CRAN/IF/ketosis to extend human life, you need to be articulate in this material. I’m always game to entertain questions. I know I’m going to get some peanut gallery commentary on this, even if it is simply directed to other folks sites or inboxes. Instead of running around asking folks what their “opinion” is on this stuff, dig in and get comfortable with the material, and you will have a better chance of understanding it for yourself.

Evolutionary pressures dictate how a species may deal with scarcity. In certain cases, like mice or laying eggs for fruit flies, the energy input for offspring is significant enough that if calories are too limited, the organism will go into a state of dramatically slowed aging in the hopes of making it through the lean times, and then making babies like crazy. Humans, do not operate this way. We do experience decreased fertility when under caloric stress, but we do not see the longevity effects. One could live barely above starvation level, and the max increase in lifespan is estimated to be about 6-7 years, not several decades. Here are two papers from longevity expert Michael Rose, talking about all of this.

Paper 1 “Why Dietary restriction substantially increases longevity in animal models but won’t in humans”

Paper 2 “Caloric restriction does not enhance longevity in all species and is unlikely to do so in humans”

I mention this as some folks in the LC camp point to ketosis as mimicking the effects of CRAN or IF. That is completely true AND almost pointless as an argument for improving longevity when we consider genetic reaction norms and the work of Michael Rose. We are mimicking a metabolic state which is now understood to be ineffective at increasing longevity in humans to any significant degree. Six years appears to be the estimated increased lifespan of severe calorie restriction and/or intermittent fasting (eating one week, not eating the next). Prof. Thomas Seyfried has done work indicating if we want to see a solid therapeutic benefit from ketosis/CRAN/IF, we need to do them in a very severe manner. Likely worth it to battle cancer, not sure that it is worth it to gain an extra 6 years of life, especially when one considers how dramatically a calorie restricted ketogenic protocol, or eat one week, skip the next week, would impact our quality of life. This all seems really dubious when we overlay the fact exercise seems to increase lifespan by about three years. We get 50% of the benefit of the most severe CRAN/ketogenic protocol, yet can be jacked, and have a life.

When I first started reading the literature on IF, I had an idea that perhaps an alternate day fasting protocol could give one a nice boost in longevity, while maintaining good performance and quality of life. This was back in 2002 when the only data we had was in small animals. As data has come in regarding larger primates, the benefit of these protocols is simply not there. The genetic reaction norms of mice and men are too different to see these same benefits in any type of a livable protocol.

So, Low Carb is bad, right?

As sure as the night follows day, some folks will read this and the take-away will be that LC is bad. DESPITE my description of LC as a valuable therapeutic tool for a variety of conditions. Folks just want a black/white world. If your takeaway from this post is that I think LC is bad I will pray that you are circumcised by 1,000 desert fleas. (I wrote this piece BEFORE all the gnashing of teeth that led to my Part 2 scree. Prescient, I’d say!)

So, what Are some situations in which LC is valuable?

1-Insulin resistance/diabetes both type 1 and 2.

Lowering glycemic load can be incredibly powerful in reducing inflammation and metabolic derangement. One could likely get as much benefit from a moderate LC approach (75-100g/day) as a strict ketogenic approach. The study by Staffan Lindeberg looking at a paleo diet in Type 2 diabetic heart patients had carb levels even higher, and folks saw remarkable improvement in insulin sensitivity. In addition to our knowledge that overeating is likely the impetus for insulin resistance, Mat Lalonde has made the point that nutrient deficiencies are also a big factor in all this. If we have inadequate substrates for antioxidant production, ROS species increase inflammation, which itself deranges metabolism and insulin sensitivity, regardless of calorie intake.

2-Neurodegenerative diseases. Parkinson’s, Alzheimer’s and other conditions seem to really respond to a very LC/ketogenic approach. It looks like we might actually get some studies in this area, which is good considering the growth of these conditions. Ketosis seems to stabilize calcium homeostasis in the brain (important for mitigating oxidative stress), and provide an alternate fuel source for glycation damaged neurons. We have seen some reports of simply adding a ketogenic dose of MCT oil in the form of coconut products, without carb restriction, actually improving some of these conditions. We have great data indicating a ketone-ringers solution could greatly benefit traumatic brain injuries (TBI), likely for the reasons mentioned above: stabilizing calcium homeostasis and providing an alternative fuel to glucose.

3-Certain cancers.

Breast, colon, prostate, and certain brain tumors http://robbwolf.com/2007/09/23/cancer-ketosis/ appear to respond very favorably to a ketogenic diet due to limiting glucose for these tissues. Unfortunately not all cancers respond favorably to ketosis, some in fact become more aggressive as the cancer is “stressed” and appears to start shuffling it’s genetics to become more adaptable. Again, an important area of research that hopefully gets more attention. AND I’ll make the point that if we want research in these areas (certainly makes sense), LC proponents might consider not acting like religious zealots, conducting personal attacks, etc.

4-Hormetic stress

I do not think that prolonged ketosis/CRAN/IF is going to dramatically extend human life. I DO think that dropping into ketosis (via a cyclic low carb diet) or occasional 16-18 hour fasting is a great way to maintain metabolic flexibility and perhaps forestall some cellular aging. My problem in saying this however, is the people who should do it (reasonably sedentary desk-jockeys with low stress) will not be the folks doing this. It will be the 2 a day Crossfit games people, or SEALS who are so type-A they cannot see the forest for the trees. If you have a high demand training schedule, you are getting all the hormetic stress you need via exercise. You are likely training at a level that is already beyond the genetic norms for health and longevity. LC, fasting, etc is NOT a smart addition to your game plan unless tanked adrenals are a personal goal.

What are Some wanker moves with regards to LC?

1- CrossFit or very hard training while LC or ketogenic. Crossfit burns through glycogen like nothing else I can imagine. If you are going to do it, you need carbs, quite a few of them. If you are trying to be competitive I’d get at least 1.5-2.5g/lb of BW most days. Obviously with the normal caveats of trying to get those carbs mainly in the PWO when/if possible. I know most folks know Peter Attia, and have likely followed his ketogenic training program. Peter is a good friend and about 15x smarter than I am. He is tinkering and experimenting, but even he has noticed he must supplement with carbs or he has no “low gear “ (glycolysis). Tinker if you want to, but my gut sense is that we will not find a magical fuel source in LC unless your activity is ultra running, or similar very long but low intensity activities. If you do MMA, CrossFit, etc, I do not think LC will work. If you are a strength athlete, I think CLC is the bee’s knees. If I was not doing BJJ and just lifting and doing gymnastics, I’d be all over this. (I wrote all this prior to part 2. It’s a bit redundant at this point, but hey, electrons are cheap.)

2-Not realizing LC is a tool. This should have actually been #1. Please, don’t shit the bed on this.

What about ME!? What about MY needs? Or the Unique Snowflake Section

A couple months back we did a series of flow charts to help folks navigate specific issues like fat loss, muscle gain and optimizing athletic performance. You can grab those here, you just need to sign up for the newsletter. Those flow-charts actually are short hand for this entire series in that they will help you dial in your macros for your given goals. In reading the comment of Pat (from part 1) however, I see folks making some consistent mistakes with regards to FAT loss. They are focusing on the scale and not on measurements and performance goals. I talk about that here and here. Read, ponder! The Truth is Out There.

Even though I cover damn near every contingency in the flow charts and two posts I linked to, I’ll cover some specific macro considerations here:

1-Regardless of your goal, shooting for ~1g of protein per Lb of bodyweight is a solid place to be. If your goal is fat loss you will find this very satiating and anabolic enough to prevent most muscle loss under calorie restriction, especially if you are doing resistance training (you better be!)

2-Carbs: if you are insulin resistant (TG/HDL >1.0), doughy through the mid-section, under severe sleep debt, you should keep a handle on your carbs IMO. 50-110g per day should be plenty, try to get this from low-ish glycemic load sources such as onions and carrots (just suggestions, use whatever you like).

If you are training hard and insulin sensitive (not carrying fat at the midsection, no wacky blood work with skewed triglyceride/HDL ratio, you should be doing anywhere from 1-3g of carbs/lb of BW. Obviously the 3g is for folks who are training at a very high level, we want this to be “paleo” carbs more often than not. White rice is likely fine but it sucks compared to sweet potatoes. Just saying. I’m doing grappling 3-4 days per week, 2-3 days per week of lifting and I’m likely getting 250-300g of carbs per day and I weigh about 175lbs. Some days less, occasionally perhaps even more. I tend to only have a bit of carbs with breakfast, then I hammer down at my post jits meal, same at dinner time. If I travel, get sick, or miss training, I just dial the carbs down a bit.

3-Fat: I mainly use it for flavor at this point. Most sweet potatoes get a healthy slab of grass fed butter, and I use grass fed cream in my coffee. Given my very glycolyticly demanding sport however, I consume less of my cals as fat than when I was just lifting and doing gymnastics. This is where the tinkering comes in…If you are not recovering you likely need more carbs (and to look at periodization, intensity, and sleep!); if you are porking out, perhaps you need to dial all the cals back, while trying to maintain protein levels.

What about Calories?

Jamie Scott (That Paleo Guy) did a great 2 part series: Calorie Rants and Ketosis Part 1 and Part 2. Give those a read, they are very good. Jamie takes me to task on an important point. In Part 1 of this series, I made a statement to the effect “Calories matter.” Jamie is/was concerned that the focus on good old calories would push some people into calorie COUNTING instead of focusing on whole, unprocessed foods. They will avoid meat and nuts entirely for fear of the calorie costs of these food, missing entirely the satiating properties, to say nothing of the superior nutrient densities. I wish I could just sweep this under the rug and say “Ah, that won’t happen, people are generally smart…” but I’d be fooling myself, and ignoring the obvious lack of reading comprehension in part 1. Some people WILL read what I said and take that in the entirely wrong direction. I try to mitigate this by relying on VERY general guidelines (you see this in my book, the Quick Start guide, and the recommendations I’ve made above). As a coach I like basic food logs, especially if they are nothing more than a photo of each meal. With a quick look at a meal photo I can tell a person to “dial back” or “add some more” and we can get remarkably good results form this. No magic 40/30/30 numerology or food scales necessary. Which is why a comment in Part 1 of my piece AND in Jamies part 1 is troubling for me:

“I agree, there must be a limit somewhere. I think the only way to really answer it is by experiment. The other thing that seems to be conflated in this discussion (not you, just in general) is whether that limit would ever be reached by a person eating ad libitum, but under the constraint that they have to stay ketogenic (not just what they think is ketogenic, but what is measureably so). It is one thing to say you can eat endless amounts of fat, and quite another to say that there is no amount of fat that you will want to eat that would make you fat. It’s possible that the latter is true even if the former is not.”

What I take from this is “If one TRULY stays in ketosis, is it IMPOSSIBLE to over eat?” My gut instinct is to say “No, I can find you people who can over eat, even in “nutritional ketosis.” But this is an opinion, I have no RCT to back this up. What I find intriguing from the simple interface of coaching/helping people is: How is this ANY easier/better than the basic eyeball method I have outlined in, again, my book, quick start guides etc. How much DETAIL will be necessary to guarantee we remain in nutritional ketosis? I hear the food scale getting pulled out, right along with the measuring cups. This seems neither easier nor better, and as I’ve said elsewhere, food neurosis REALLY kicks in when folks start scrutinizing their food as is typical in the CrossFit world of the Zone, or in what would be necessary to fit the standards here of ensuring nutritional ketosis. This feels vaguely of trying to make some kind of religious ritual produce a measurably beneficial effect in the real world…perhaps I’m missing something, but this line of inquiry seems to be valiantly trying to find a way to make ketosis magic.

I hope this helps clear up some of the drama around LC and Paleo. I see the evolutionary template as a means of making informed decisions about how we eat and live to optimize performance, health, and longevity. I see LC as a tool to be used for specific situations, and to achieve specific goals. Hopefully, a day will come when NONE of this is controversial or still adhered to with religious dogmatism. Someday ketone-ringer solution will be the go-to IV for folks with TBI. Ketogenic diets will be used in conjunction with standard chemo and radiation to not only fight cancer, but protect normal tissue from the damage these blunt force tools offer. Primary care physicians will recognize the therapeutic value of LC for insulin resistance. World champion athletes will still, for the most part, be carb fueled.

Remember, hammers are just as important and valuable as screw drivers. It just depends on what the project is and what we are trying to do.