Thursday, January 22, 2015

Diet Soda Changes Gut Bacteria

Diet Soda Changes Gut Bacteria

Many people, including, I'm guessing, most weight loss doctors, have an instinct that diet sodas are a bad idea, but it's been hard to find research that would back this up. While it's true that diet soda and obesity are associated, it seems reasonable to suspect that people turn toward diet drinks because they are getting heavier, rather thinking the weight gain is in any way due to the soda. A previous myth was that the brain-gut-pancreas system couldn't distinguish artificial sweeteners from the real thing, so that drinking diet soda would cause insulin spikes, that over time would lead to obesity. That's been disproved. However, a scientifically sound reason to avoid diet soda has been found.

In this thoughtful series of experiments reported in Nature last fall, the researchers show that diet drinks may sabotage weight loss efforts and hasten diabetes onset through encouraging the growth of unwanted species of bacteria.  Suez and colleagues studied whether saccharin, sucralose and aspartame would alter the composition of the bacteria that live in 10 week old, lean mice.  They compared the artificial sweetener group to controls drinking water, water + sucrose and water + glucose. The mice drinking water, sucrose or glucose had similar glucose tolerance curves falling in the normal range. They continued to handle blood sugar well, so would be low risk for diabetes. All three of the artificial sweetener groups developed glucose intolerance within weeks. When they combined the saccharin feeding with a high fat diet, they produced obese, insulin resistant mice. They went on to examine the composition of microbiota in the feces of the mice and found that the artificial sweetener groups had overgrowth of unnatural bacterial species of many types. They then demonstrated that they were able to transfer the glucose intolerance from the sweetener group to the healthy lean group by fecal transplantation. The researchers then went on to treat the mice with antibiotics (ciprofloxacin and metronidazole) and found that the changes in tolerance to glucose were reversible with antibiotics.

This is a remarkable series of findings which strings together several proposals:

            1. Artificial sweeteners cause glucose intolerance
            2. The glucose intolerance is mediated by gut bacteria
            3. Glucose intolerance is "infectious" through fecal transfer
            4. It is reversible by antibiotic treatment.

So which comes first, obesity or diet soda drinking? This study didn't directly address that, but it gives a biologically plausible explanation for ill effects of artificial sweeteners on our metabolism. With regard to obesity specifically, the experiments have been fairly convincing that bacteria play a role (for example: V.K. Ridaura et al., Science 341, 6 September 2013)  In mice, there is evidence that fulfills roughly all of Koch's postulates: fecal transplants from lean and obese humans will produce lean and obese mice with differing intestinal flora. If you take a lean mouse and have him live with the obese mice, he will not grow heavy, but if you take an obese mouse and put him to live in the cage with the lean mice, he will lose weight. This bodes well for the pressing problem of mouse obesity.

In humans, the prospect of fecal transplant is being tried experimentally and when it becomes accepted, I will try to be one of the first to open a walk-in Eat S*#T! clinic on a busy urban street. Until that time, we are stuck trying to guess which dietary factors to manipulate in order to change the bacteria from "obesity prone" to "obesity resistant" colonies. This paper lends support to the idea that bacteria affect our weight and glucose handling and that it may be worth actively searching out certain microorganisms to aid our metabolism.

Still, It's a long way from there to an obesity cure. I've always been sort of amazed at people's willingness to ingest yogurt because it has active cultures of bacteria in it. I think a bit of skepticism is warranted by consumer. If it is a good bacteria in the yogurt, good for what? And shouldn't one get a stool sample to see what one's levels are before trying to add an organism to the mix? What would be the right dose? Can we just hope that the bacteria will duke it out and that some magical balance will occur with more "good" bacteria than "bad"? Are you sure that you are in need of more L. delbrueckii subsp. bulgaricus in your diet? Do you trust the yogurt makers to decide that?

Don't get me wrong, I like yogurt, but not for the bacteria included.

If there were to be clinics which specialized in fecal transplant, before and after tests would likely be routine, so maybe over time, we would find the answers to the above questions. For now, we will have to wait for some human trials to reproduce the mouse proof of concept studies.

Wednesday, January 21, 2015

Can Sugar Free Red Bull Aid in Weight Loss?

People seem to have one of two opinions regarding Red Bull: either you hate it, because it tastes like someone added carbonated water to a fistful of SweetTarts, or you love it, because it tastes like someone added carbonated water to a fistful of SweetTarts. I myself fall in the second camp, but don't drink Red Bull regularly because it sends my heart rate up enough that I fear it contains something illegal, or at least dangerous. The non-caffeine stimulants in the drink are what give me pause: taurine, glucuronolactone and B vitamins. These are what distinguishes the "energy drink" beverages sector from the soda sector. The presumed increase in energy from the alternative stimulants is their appeal. That combined with the fact that people base jump with Red Bull parachutes, so the brand is undoubtedly "cool."

With regard to diet drinks, the hypothesis is that taking in caffeine without any sugar should lead to weight loss. While normal high sugar sodas contain enough calories to more than counterbalance the benefits of the caffeine, sugar free sodas should, theoretically, provide a net calorie burn. Caffeine increases metabolic rate, so a calorie free caffeinated beverage should help weight loss (It doesn't, but that's discussed in the next post). What we are discussing here is whether Red Bull's other ingredients do anything in addition to the caffeine.

The authors took healthy young men who were daily caffeine drinkers and gave them either sugar free Red Bull or the same amount of caffeine in simple water. This was designed to test whether there was anything else, besides caffeine, changing metabolic rate. What they found is that the Red Bull drinkers and the water + caffeine drinkers experienced an equivalent rise in resting energy expenditure of 4 percent that lasted about two hours. There was no difference between the two groups, so the researchers concluded that the taurine, B vitamins and glucuronolactone did not have an effect on energy. 

Red Bull, Monster, Rock Star and 5 Hour Energy are all utilizing caffeine to give an energy boost, or even a "rush" that we will view positively or negatively based on our view of how it feels to be artificially sped up.  They are different from sodas not due to the fact that they contain a collection of other purported stimulants, like Taurine or Guarana, but simply because they contain the equivalent of three or four sodas in each serving. Instead of a soda, you are getting something that tastes sweet but has the caffeine of a double espresso.

Getting back to weight loss, are sugar free energy drinks a good idea? The 4% increase in resting energy expenditure seems promising, but we need to recall that our resting energy accounts for roughly 60% of total energy. If we raise that 60% by 4% for two hours, we would likely not make a dent in the overall daily numbers. If we were to drink the Red Bull every two hours while awake, a 4% change in energy would certainly be significant, but then we'd run into an unpleasant side effect profile that most coffee drinkers know well: irritability, lack of focus, racing heart, impulsive online purchases (that may just be me) poor sleep, etc. 

It's worth noting that majority of over the counter weight loss products use caffeine  as the main active ingredient, including many that the FDA has banned due to cardiac side effects. But assuming one is only going to have one or two Red Bulls or other energy drinks per day, I doubt there's any harm. If you like the taste, go ahead. Just don't expect to see a major change in your weight when switching from the sugared to the sugar free version.

Friday, June 27, 2014

Ketosis Does Not Improve Weight Loss

This is part 2 for "Adherence predicts weight loss."

Almost every physician believes that weight loss is about "calories in/calories out." We learned in med school that the ATP cycle can be driven by fat, carbohydrate or protein and that, as far as our mitochondria are concerned, "a calorie is a calorie." As a physician trying to uncover the mysteries underlying weight gain, over the last ten years, I've searched far and wide for other explanations for obesity and found many leads, many interesting side stories and many dead ends. I've learned that the macronutrients (carbs/fats/proteins) are processed differently in the gut, have differential efficiencies for creating energy and may serve different roles in health. I've been inclined to discount the pure mathematical truth I learned in medical school and to espouse a philosophy a little bit outside of pure science: Carbohydrates are the cause of obesity.

For many readers this may seem obvious. For trainers and weight loss doctors, this is a statement of fact. Most assume you can't be lean unless you cut carbs. But for physicians, who read randomized controlled trials, meta-analyses and evidence-based guidelines...the low carb-diet trend is unsound, a fad, not scientifically validated and perhaps, quackery, sold by doctors who want to get famous (Atkins, anyone?). It was with great trepidation that I slowly adopted a "carbs are evil" message in my obesity clinic. A little sheepishly, I began to suggest to patients that their weight problem stemmed not from how much they ate, but what they ate instead. I initially was quite embarrassed to espouse these views as they flew in the face of most randomized trials which showed results that seemed to never back up low carb claims.

When I suggest to patients that they consume a higher protein/lower carb diet, it does, in fact work. It's a good way to eat to lose weight. But we need to ask, is it because you eat fewer calories, or because something changes metabolically to make weight loss easier on this diet. The explanation used by Atkins and most low-carb advocates is that, without carbs, the body must use fat as a source of calories. The brain must have sugar or ketones to function. Protein can't get in there. Generally, it's easier for the body to convert fat to ketones than it is create sugar through disassembling the carbon atoms in protein, so it will go into "ketosis" after a few days after removing carbs from the diet. "Ketosis" is considered the magical land of "fat burning" and is generally the "metabolic switch" that fad diet books talk about.

As a follow up to the previous post on adherence, I now have mathematical support that ketosis does not represent a state of "fat burning" beyond what would be expected from calorie deficit. As I mentioned, we tracked clients on a minimal carb (less than 50g), higher protein (over 100g), low calorie (about 1000) calorie diet and compared their weight loss over various periods with predictions from a purely mathematical model. The model has a slight increase in weight loss for low carb based on the actual weight of glycogen and can account for salt, but the few pounds are a question of water balance, not anything metabolic, like a "faster metabolism." In short, the model doesn't "believe" that ketosis has anything to do weight loss. Weight loss is caused by calorie deficit, period. The model is, basically, a big bummer for weight loss doctors like me, who want to espouse special knowledge.

So, why do I say that ketosis doesn't matter? Because without accounting for any acceleration in fat burning due to a different metabolic process, the model predicted weight loss nearly perfectly for the participants. There was not one patient who had a surprisingly rapid weight loss that would suggest any metabolic magic was causing an increase in fat burning. Using simply "calories in/calories out" math, we were able to predict how the individual bodies would react. The model, knowing nothing of mitochondria, insulin, leptin, ghrelin, CCK, PPY, Agouti-related protein, NPY, hormone sensitive lipase (I could go on) - the model predicted weight loss just using calorie deficit. None of the hormones that interest obesity researchers mattered in this analysis. Knowing calories and some basic facts about the size, age and activity of the clients was enough. Certainly nothing as simple as "turning on ketosis" contributed to the results.

So what are obesity experts talking about?

The researchers aren't trying to figure out "why" we gain weight. They are doing what scientists do. They are working out "how." All those internal hormonal signals certainly are the controllers of our metabolism, but they merely explain "how" it happens. The "why" is still all about calories. The answer, until someone develops a suite of medicines to manipulate the above hormones, will remain calorie restriction.

So, does this mean we just need to reduce calories and forget about trying to find a diet with the right composition? Probably not. Just because a lower carb/higher protein diet doesn't turn on a magical weight loss switch doesn't mean that it isn't helpful for a different reason: this diet makes it easier for many people to eat fewer calories. Getting rid of carbohydrates helps curb cravings. Eating protein makes you feel full. Taken together, those two things can help you eat less. But that's probably the extent of the magic.

This is not a conclusion that makes me happy to realize, nor does it help me advertise my weight loss clinic. Which is why I'm pretty sure it's accurate.

Monday, June 9, 2014

Adherence Predicts Weight Loss, Part 1

I've recently had a very unsettling experience
I've just published, collaborating with Kevin Hall (whom I mentioned in the blog pieces on Obesity Math), an article testing whether simple "calories in/calories out" calculations are useful. The article, "Is Mathematical Modeling Applicable to Obesity Treatment in the Real World?"  is out in the June issue of the journal Obesity. The unsettling aspect of the paper and the analysis of our clients is that when you can assure compliance to a weight loss program, the body acts pretty much like a machine.

We looked at a database of clients participating in a supervised medical weight loss program with meal replacement. This program is terribly strict, supplying most of the food to the clients and asking only that they supplement with two cups of fresh vegetables and a "real" protein source of chicken, lean beef, or fish for dinner. Strict adherence to the diet provides between 900 and 1100 calories. It's a low carb, low fat, low calorie diet, that is, by design, also a higher protein diet...since you cut everything else.

Whether the clients are adhering to the diet is pretty simple: if they lose a ton of weight, they are adherent. This is way too few calories for pretty much everyone, so if your patient comes in having stayed the same for the week, you can be pretty sure there was some deviation from the program. We reviewed records from over 100 patients and found 49 for whom compliance seemed very tight for at least four weeks, based on the clinic notes which review the patients' self assessment on how close to protocol they've been. Then we asked:

If one is extremely compliant to a rigid diet program, does the weight loss match what a mathematical model would predict?

The reason this is even in doubt is that pretty much every mathematical model will over-estimate the weight loss seen in a real, outpatient, free-living subject. Kevin and I wondered if that was due to some inherent flaw in these models, or whether free-living people are simply never compliant with recommendations (actually Kevin probably didn't wonder at all, because he's a scientist, but I'm just a clinician, so I really wondered if there was some mysterious explanation of variable weight loss outcomes). With this very strict regimen and the close follow up, we were able to see how the weight loss of truly compliant patients added up. We plugged patients' height, weight, age and activity level into the NIH body weight simulator and asked the program to predict how individual's weight loss would progress on the reduced diet. We excluded patients who admitted to straying from the diet.

The unsettling part is that the weight loss for patients who were able to be strict with themselves was essentially exactly as predicted. As the paper shows, the correlation between predicted and actual weight loss is remarkably close (R-2 of .816). Basically, for everyone who could maintain this diet (and don't get me wrong, I could never maintain this diet, I've tried and lasted 6 days on my best attempt), the body works in fairly perfect thermodynamic harmony. A calorie, unfortunately, and I say this with great regret, because it breaks my heart so, is actually, a calorie.

Why do I find this unsettling?

Because for me, it's quite a surprise. I've made a career out of weight loss counseling and that involves being able to work with people month after month, whether things are going well or not. I don't demand rigid adherence, but simply a good attitude and the ability to show up for the recheck appointment. I have patients who plateau on weight loss for months and months. I spend a good deal of time speculating on the biological basis of plateaus, since we do in fact, have evidence that many hormonal controls in the body react to counteract weight loss (leptin decreases, ghrelin increases, etc). What the data in the paper tells me is that, regardless of the biology, plateaus and rebound weight gain come through the patient overeating again. When we are consistent, the weight loss will not, cannot, fail. If the data in the study came back all over the map, not in line with the computer model, I would have said, "see, the body is complex, everyone is different, we all need individual solutions relating to our unique biology." But the opposite seems true: the bodies of our subjects behaved almost exactly as expected, with almost no variation.

The question turns from "how do we better understand the biological signalling responsible for weight control?" to simply "how do we get people to follow the rules?"

Monday, October 28, 2013

Yo-Yo Dieting, Is It Bad?

Yo-Yo Dieting, Revisited

There is a bit of folk wisdom in the U.S. that “yo-yo” dieting, wherein a person loses “the same 20 pounds” over and over again is somehow bad for one’s health. I think Oprah taught us this, I’m not sure. There has really never been any scientific data that would support this view, just some guesses about what this might theoretically do to one’s metabolism. Personally, I like to experiment with diets to see what works and what doesn’t and have tried most of the things I suggest to my patients. I lose and regain the same 8-10 pounds a few times per year. After reading a paper I came across about body composition recently, I’m going to stop doing that. I’m worried I might be creating a weight problem, here’s why:
The article,“Is lost lean mass from intentional weight loss recovered during weight regain in postmenopausal women?” was published in the American Journal of Clinical Nutrition in 2011. The authors, (Beavers, et. al) used DEXA scan before and after weight loss to investigate what is lost when patients lose weight. They found that the women were losing about 70% fat mass and 30% lean mass. This is good news, it means we get leaner as we get lighter, which has multiple metabolic benefits, including an improved metabolism (since lean mass uses more calories than fat mass). But, knowing that weight regain is inevitable in most people who lose weight, the authors asked the women to recheck in one year. Sure enough, 3/4th of the participants regained weight after 12 months. Scanning the weight regainers again with DEXA showed that the pounds that came back on were composed of 90% fat mass and only 10% lean.
The regained weight was not “the same 20 pounds” but 20% fattier pounds. Since the participants didn’t, on average regain all 20 pounds, the women were still leaner than before they started. But what if the study was run for two or three years, until ALL of the weight that was lost was regained? What if these women repeated the diet attempts over many years, in typical yo-yo fashion?
********Now we are discussing my speculations, not what’s reported in the paper***********
I  took the numbers from the study, converted them to pounds, rounded up to 200 (from 197) as a starting weight and put a hypothetical average patient through five cycles of weight loss and regain of 20 pounds:

The weight fluctuates up and down through cycles of loss and regain over a few years, let's propose. The person dieting feels stuck, battling what seems to be inevitable biology bring back the same 20 pounds. Most individuals likely assume that it's simply fat that's lost and regained, never stopping to wonder what's the composition of weight in either direction. Hypothetically, the body is losing 70/30 ratio of fat to lean and regaining 90/10 ratio repeatedly, so that over several cycles, the weight seems the same as it always was, 200 pounds, but the ratio of lean to fat mass has been much worsened by the diet attempts:

As the 200 pound person loses lean and fat and regains more fat than lean, after five cycles, the internal composition of the person has gone from being more lean than fat, to more fat than lean. This is totally invisible on the scale and mostly invisible on the body, except that one's shape presumably is a little worse in terms of belly bulge. This process is likely happening to all of us as we age in subtle ways. Whose belly looks the same at 50 as it did at 20? But the accelerated process of "fattening" could be part of the reason that losing weight gets harder after many attempts, rather than easier.

I ran all this by a researcher who is a lot smarter than me on this stuff and he was skeptical that the original DEXA data were accurate enough to build the case I'm making here. The scans are prone to error in terms of hydration. With that caveat in mind, the 70/30 loss, 90/10 regain issue should at least be considered by people wanting to lose weight. It fits my own reasoning that I share with patients: if it takes decades to gain 100 pounds, presumably, one's body built up the muscles that are needed to support the new weight in a fairly predictable pattern. If we suddenly reduce, then suddenly regain, would the body be able to lay on the muscle in an accelerated fashion?

One follow up study that would help to confirm what I'm proposing above, would be to DEXA scan a group of heavy patients and see whether those who report many large weight loss success in their past, with regain of "all the weight and more" have worse lean/fat mass ratio than those who are of same weight, but no previous weight loss attempts.

Monday, August 26, 2013

Book Review: The State of Slim, by J.O. Hill and Holly Wyatt

The authors practice, perform research and teach in Colorado, a state known as a perennial laggard in the race toward 100% obesity rates. The title refers to the fact that Coloradans have some advantages when it comes to staying slim: good weather, a landscape that invites exercise, excellent access to nutritious food and a culture that supports, rather than undermines, healthy choices. They argue that the rest of us can learn from this Mile High state of mind and keep, or regain ,our health by following their clear diet and exercise recommendations.

This is a diet book, written by scientists, for the general public. It’s a quick read and only mentions particular studies in passing. But it doesn’t avoid a quick review of the latest understanding of obesity including that:

  • Obesity is a disease
  • Obesity does have biologic causes that are understood
  • Metabolism is different in the obesity prone
  • Weight regain is inevitable for most, due to hormone responses to dieting
  • The overweight and the normal weight do not eat that differently

All of this is a refreshingly sound introduction to the main purpose of the book which is the diet program. It reads like a very complete handbook you’d receive on starting a medically supervised weight loss program and I suspect that’s where much of the material had its origin. This is to say, it’s an awesome handbook you’d receive if you started an awesome supervised medical weight loss program. I’ve been recommending it to my patients who lack such an awesome handbook in my somewhat-less-awesome weight loss program in Iowa.

The diet is based on the following:

  • Eat six times a day
  • Have breakfast within an hour of waking up
  • Don’t count calories, measure portions
  • Have the right carb and protein mix at every meal
  • Eat a healthy fat twice a day

There are three phases, including an induction phase that is similar to Atkins, in that it’s designed to cause a ketotic state that yields a quick jump start to the program. It’s very low carb (the only carbs come from vegetables) and causes 8-10 pound weight loss in 2 weeks. The second phase adds back grains, but focuses on whole grains, brown rice, barley and quinoa. This is while slowly building up to 70 minutes of exercise daily over 6 weeks. The 3rd phase is where you really don’t have many restrictions, you just eat the healthiest versions of protein, fat and carbs, like you should have been doing your whole life, if you didn’t have a weight problem. Phase 3 in this program is basically where any dietitian would start you on a weight loss journey and it would probably be too slow and you’d stop doing it. In the Colorado diet, you’ve been ushered through the first two phases and have given up enough of junk food that the final reasonable suggestions in phase 3 are probably more likely to be permanent changes.

Some may object to the recommendation of 70 minutes of exercise per day. But the recommendation is based on the observation of real life successful weight losers in the National Weight Control Registry, so it’s difficult to argue with the fact that it seems to be this enormous amount that’s correlated with long term success. The authors point out that the exercise really hasn’t been shown to be the key to weight loss, but that it seems essential for preventing weight re-gain.

I’ll continue to recommend the book as a sound outline, with practical lists of foods to increase in the diet that I would agree will cause weight loss.

Tuesday, August 13, 2013

Blue Zone Proponents Beware: increasing activity doesn't help obesity rates.

Ali Mokdad is the researcher who first turned the mortality rates in the U.S. upside down and sideways by rearranging the normal causes of death to account for risk factors, rather than disease state at time of death. By tracing heart disease, cancer and stroke to their true underlying causes, the top three actual causes of death were determined to be tobacco, obesity and alcohol. 

Instead of this:

We should consider this:

Whether the methods of attributing a death to these risk factors are accurate in a mathematical sense is debatable, but the paper that first presented these numbers got a number of us MDs, including myself, to think about the root causes of disease. In fact, that paper decided my career path. In any case, Dr. Mokdad’s group recently published a paper on the relationship between exercise and obesity that may help people to think differently about this question too. In Prevalence of physical activity and obesity in US counties, 2001-2011: a road map for action, the researchers demonstrate that increasing physical activity, on a population level, is unlikely to lower obesity rates significantly.

They took survey data from the Behavioral Risk Factor Surveillance System (BRFSS) and the National Health and Nutrition Examination Survey (NHANES) to assess how well activity patterns correlate with obesity patterns on a county by county level. This is a closer look than has ever been published previously and combining the two surveys allows them to correlate the behavior data in BRFSS with the measured BMIs in NHANES.

What they found is that there is almost no correlation between rising activity levels in particular counties and improvements in obesity rates in those counties. They conclude that “for every 1 percentage point increase in physical activity prevalence, obesity prevalence was 0.11 percentage points lower.” Unfortunately, they don’t explain, “lower than what,” but by reading the paper three times (once with contacts, once in bifocals and once just taking glasses off altogether) I’ve deciphered that they mean “lower than the rise in obesity that would have been expected.” So they are talking about a very slight decrease in the rate of increase in obesity, for those counties that saw increased activity. And the percents show a 10:1 ratio, so there is actually just about no value, in terms of county level obesity rates, in increasing activity level on a county level. They didn’t say that counties with more exercisers didn’t have a lower baseline obesity rate (they generally do), but simply that the cause and effect you might wish for if you were applying for a grant  (that your program to build bike paths will reduce the county obesity rate) is hard to find in the data. We don’t know if all those people in Douglas County, Colorado are skinny because they hike and bike so much or whether all the skinny hikers and bikers move to Colorado to do that stuff there. What we do know is that the counties that saw the biggest increase in activity did not become skinny and those that decreased activity did not become heavier than expected.

Other things they did not show:
  • Increasing activity does not help individuals lose weight
  • Increasing activity does not lower risk for diabetes, heart disease, stroke
  • Increasing activity does not improve fitness

They are not arguing that exercise is bad for you, or not worth while. But they are saying that simply getting people to follow the public health recommendation to exercise for 150 min per week is unlikely to do anything for population obesity rates. I find this to be totally logical and in line with what I know about obesity on an individual patient level. I don’t walk into a patient room for a weight management visit and say “tell me about your exercise habits, because you’re really heavy, so we need to figure out your exercise problem.” We talk about food and we solve the food problems. But for some reason, people don’t think that way about the public’s weight problem.

It’s a misconception of the 10-20 pound overweight public policy makers that obesity is synonymous with being “out of shape.” Small weight problems can respond quite well to doing a little exercise. But obesity is a disorder of the metabolism. It’s caused by changes in the food environment. It’s not cured by exercise, or anything else that doesn’t address the food environment. When it’s curable, it’s cured by radical changes in diet, or surgery.  Exercise can help a person “get in shape” while they are losing weight, but that is a peripheral issue to weight loss. I have countless patient histories that show this to be true and now I finally have a decent public health study that shows it on a larger level.

I just don’t know why the title wasn’t: A road map for in-action.