Stephan Guyenet coming on the podcast – submit your questions!

May 4, 2011 in Events, Classes & Groups | 46 comments

picture of stephan guyenetDr. Stephan Guyenet will be joining us again on the podcast to discuss his developing theories on obesity and weight regulation. Stephan is a researcher at the University of Washington studying the neurobiology of fat regulation. He also writes one of my favorite blogs on nutrition and health, Whole Health Source.

If you have not already, I recommend you listen to my first podcast with Stephan. This show will build on material we discussed during the first interview.

Please leave your questions for Stephan about obesity, body fat regulation and weight loss in the comments section. We’ll be recording the interview on 5/13, and it will air on 5/24.

{ 46 comments… read them below or add one }

Hamp May 4, 2011 at 8:44 am

I just love listening to your science!
But so far in all my own research, I have not been able to find definitive answers to a few things. I’d love for your opinions on these:
1. How do you reconcile the different recommendations for a paleo approach of eating high fat (Wolf and others) vs low fat (aka DeVany)?
2. Is the glycemic index truly worthless or is there any merit in their numbering system at all?
3. Does it help to have some protein/fat WITH a fruit to less the sugar absorption or not? (I’m so hoping; I do love an apple with almond butter or a hard cheese)
Thanks for all your work,


Nick May 4, 2011 at 12:54 pm

I could be completely off base here but with regard to your questions about high fat vs low fat….
If you listen to Robb, he isn’t saying to eat a High Protein or a High Fat diet.. or a Low Carb diet for that matter.. I really Depends on your activity level.. If you are a hard charging crossfit athlete who wants to stay low carb, then you will need to increase your fat intake… or the same athelet might go higher carb in the sources of roots, tubers etc and stay at moderate fat and protein levels.. You have to find what works for you and your goals.. Hope that helps


Lstrathm May 4, 2011 at 8:49 am

In his blog, Dr. Guyenet has been teasing a new approach toward weight loss. He says, “I have a simple new idea that I feel confident in. It also neatly explains the results of a variety of weight loss diets.” If he’d like to preview his new idea for your podcast listeners, I’m sure there are many (including me) who would love to hear what he’s thinking!

I love your podcast!


DKM May 4, 2011 at 8:58 am

Why do some people gain weight so easily and struggle so hard to take every pound off? The women in my family are all super active and healthy, but struggle with weight. Like my relatives, my weight went up and down in my teens and 20s, but with diet and exercise, I was able to control it, until I hit 30 when my weight ballooned – I gained 100 pounds in 8 years. I’ve since lost 60, but the remaining 40 is a struggle. A diet centered around protein, veggies and fruit with low starch seems to work but it’s still an incredible struggle! It feels like it’s impossible to keep weight off for the long haul. Oh, and by the way – diabetes is in my family – everyone starts out thin, slowly gets heavy, and then slowly gets Type II diabetes, all while struggling against this progression.


Norcal Mike May 7, 2011 at 11:49 am

related: Please articulate how one’s “adipostat” adjusts the body’s target for fat storage during different stages of life (early growth, puberty, meno/andropause, etc.). Why is it most common that one’s adipostat allows fat gain relatively easy over time, and only puts up a fight when it comes to fat loss?


Stalled May 4, 2011 at 9:06 am

I’ve had great success adopting a Hunter-gather lifestyle: I’ve lost 50lbs and regulated my insulin levels. However, in the last month, I’ve stalled out. No matter how much/little I eat, my weight remains stable. I have about 20 more pounds to go, almost excusively from my waist. I’ve played with higher fat, lower carbs and high carb variations, but to no effect. I think this is likely due to cortisol; but I’m sleeping 8+ hours/night; and eating healthy. Is the remainder simply from over-training (strength 3x/week; conditioning 5x/week). Any suggestions/tips?


ExpertInTraining May 4, 2011 at 9:10 am

Question on liver:
I’ve heard/read about the health benefits of liver from both of you; and have been convinced it needs to be an essential part of my diet. But the taste is awful. Until I acquire a taste for it, I’m using the frozen “pill” suggestion. Here’s my question- How many ounces of liver are needed for the benefit- either per day or week?


KD May 4, 2011 at 7:05 pm

I’d like to second this question. I don’t hate the taste, but I could easily live without trying to incorporate the texture into my food, so knowing the average minimum that would be adequate/beneficial would be helpful.


Kevin May 4, 2011 at 10:33 pm

+1 on liver consumption levels.

I love liver and other organ meats [taste, price, nutrients] and I eat liver one week a month – usually 4-6oz a day over a 3-4 day period. I would definitely eat more offal more often if I had a better understanding of potential risks, upper limits, etc.

Also: I buy grass-fed beef by the side, but that only gets me ~15lbs of organ meats, so I have to supplement this with conventional meat. I know grassfed meat is preferred over grain fed, but is liver from CAFO cows uniquely bad, because of liver storing toxins, etc?


Bob Kaplan May 4, 2011 at 9:15 am

I would like to know what Stephan’s definition of set point is and if he has heard of the settling point hypothesis and if he thinks this is more apt, or not, and why?

He recently posted about water-in/water-out as an absurd solution for edema and how this same inanity is applied to calories-in/calories-out for weight loss.

But are we fighting a hydrostat when we consume too much water, and therefore more is excreted – or – does water get partitioned via hormonal mechanisms and feedback loops where our water volume generally settles at a number that we can generally determine?

Stephan wrote: “For example, if you have edema because your heart isn’t pumping effectively (cardiac insufficiency), the heart is the problem that must be addressed. Any other treatment is purely symptomatic and is not a cure.”

I wouldn’t say that our heart is fighting our hydrostat, rather the cardiac insufficiency is leading to a cascade of feedbacks that ultimately lead to edema. We want to address the problem, i.e, the heart, not the ‘hydrostat.’


Sarah Nickolet May 4, 2011 at 9:27 am

My questions are similar to the comments above, why do some people succumb to large amounts of weight gain on such little food? Which then goes on to trigger several autoimmune pathways making it very difficult to lose anything? I am similar in that I was born a normal weight baby, was normal and active as a child and young woman. At the age of 20 the weight started packing on and I too gained about 100 lbs in 4 years. I cannot get it off!! I trained HARD with a trainer for a year and while my shape changed….I did not lose a pound. My trainer was absolutely flabbergasted and frustrated. We tried tweaking all sorts of things. This is what sent me to my dr for more thorough testing. Carbs are a problem for me as I cannot stop eating once I have them but if I cut them out entirely I still cannot lose weight. I tried the no carb for a while and then “refueling” cycle to see if that would jumpstart some fat loss but to no success and actual it triggers a binge pathway for me. I now have Hashimoto’s (but normal TSH), PCOS (onset after two easy to conceive normal pregnancies), and Insulin Resistance. All because of this stupid weight! I’d love to hear Stephen’s ideas about a simple approach. PLEASE!


Tyler Simmons May 4, 2011 at 11:09 am

Very cool- your podcasts are rocking Chris!

I think this is along the lines of what you guys are going to be talking about anyway. What are the different factors that impact leptin production and leptin sensitivity?

We know that leptin production mainly reflects short term energy intake and long term fat stores, but there are some interesting theories about triglycerides and leptin, fructose, sleep, time between meals, cortisol, etc. What do you think the evidence is pointing to as the cause(s) of leptin resistance?

Feel free to edit for clarity or integrate into other questions.

Thank you!



Lori May 4, 2011 at 11:29 am

How can those of us who eat strictly paleo , whose weight loss and stalled and even reversed, and who are otherwise healthy lose the extra weight? It’s just not happening for me.

I’m trying to be more active to see if that helps, but then I hear people say that it doesn’t matter for weight loss. So what then will help lose extra weight and keep it off long term?

Do you have any upcoming lectures at the University of Washington or in the Seattle area?



Long Term LC Dieter May 4, 2011 at 12:25 pm

My doc put me on a low carb diet over five years ago, stating that it would be the only way I can lose weight due to metabolic resistance. I have lost 87 pounds over five years and five months. The experience has been exasperating and very slow. I think the only thing going for me is that I never give up. Most of the time, nothing happens. Sometimes I lose weight due to an incredible period of stress, sometimes I change my food choices 100% and have a short (emphasize short) spurt of weight loss, and once I lost weight (in the beginning) after a flu virus (I have not had a cold or the flu in 5 years now, and no cavities either, yay!). I also tend to get a short spurt of weight loss after a short hiatus, such as 3-4 days of overeating the standard american diet at Thanksgiving, and then going back to low carb, which is when the short spurt will start.

I hang in there with low carb and that weight does not come back. Again, most of the time, nothing happens. Yet, when my doc shows me the graph, it is a straight line from left to lower right because I only see him a couple of times per year. He is pleased but perplexed as to why my weight loss is so slow. He thinks I should do resistance training (weight lifting, slow with few repetitions to total fatige) and sprinting for 4 minutes (!!!!).

I think my doc is a bit crazy for suggesting sprinting since I am still 50 pounds overweight. I am sure I would tear a ligament. The last time I tried going to the gym I ended up with a small tear in my miniscus. I am not opposed to the weight lifting, but I have tried that several times in the past with no fat loss.

I hate to sit around waiting for the next stress bomb to hit me just to lose weight. I never get sick anymore, and frankly, overeating for 3-4 days once in a while results in a difficult withdrawal period to get back on plan. I have changed up my food choices 100% again and got a 3 pound weight loss. I am always looking for that next perfect idea. I agree that cutting calories just results in my thermostat going down (I freaked out and read about thyroid recently; I hate to say it, but addressing thyroid seems like voo-doo to me). Exercise only seems to work for me if I am on my feet all day walking (I suspect it is only because it helps with insulin resistance).

I assure you I do not have compliance issues with the diet. I will change my plan 100% on the drop of a hat if I think it will get me anything, as long as it is low carb.

I am becoming obsessive about the diet at this point. I am also getting older and I’m concerned I might not lose any more weight loss as I approach menopause.

Do you have suggestions for a woman in her late 40s for weight loss after long term compliance with a low carb diet to keep it going?


Victoria May 6, 2011 at 6:42 am

Hi, just a comment on the sprints. You don’t have to sprint for 4 minutes straight. Here’s what I do and it is doable and effective. On a recumbent bike, warm up for 3 minutes, pedal as fast as you can for 30 seconds, recover for 1:30, then repeat, until you have done 8 sprints. This takes 20 minutes (sprinting at the 3, 5, 7, 9, 11, 13, 15, and 17 minute marks). You are definitely tired afterwards, but feel really energized.


DKM May 6, 2011 at 7:35 am

re: sprints and injury – what about working out in the water? You can incorporate sprints into swimming laps or deep-water jogging (with a floatation belt if you prefer) if you’re worried about injury. This is a way to get a full body workout with minimal injury. I work out mostly in the water now because of my weight but also because of a chronic back injury. Anyway – alternating sprints vs. jogging in deep water works great for me.


alexandra May 4, 2011 at 12:59 pm

hay, cannot wait for the podcast!

how “dangerous” is combing high fat foods such as coconut oil, cream or butter with sugar sources? I’m referring to whole foods such as ripe bananas, raw honey or maple syrup, as I have gave up the rest of sweeteners.

I tried the low carb thing it doesn’t work for me so I incorporated potatoes, white rice, raw honey, dates and bananas. I haven’t gained any weight in over a year and I’m in a really good shape (I’m breast feeding my 2 yo and looking better than I did in high school).
but even the high fat fans are against high fat when it comes to making desserts or combining it with carb sources. Am I pushing my luck here?

thank you


Suzan Robertson May 4, 2011 at 1:05 pm

Almost all of the above questions in these comments are pretty much the same ones I have. In addition:
1. What does Stephen think about cortisol issues affecting weight loss and what can be done about it?
2. For those of us who are having a very difficult time losing weight even though we are faithfully doing Paleo/Ancestral/Primal- style eating, yet we often go weeks without losing a pound, what advice does Stephen have?
3. In that same vein, does he think that daily intermittent fasting is a good idea for significant weight loss?
4. What about coconut oil vs. olive oil? There are two schools of thought on fat within the Paleo community, can he clarify?
5. Finally, does Stephen agree with Gary Taubes that there may be some people who have broken metabolisms (from metabolic syndrome or insulin resistance, and yo-yo dieting) and that it may be “too late” for them to lose weight?

Thank you Chris. Appreciate all you do.


Long Term LC Dieter May 4, 2011 at 2:58 pm

I forgot to add –

I am attempting to lose 50 more pounds, which is a reasonable weight for me – it is the very high end of the standard weight chart for my height for a large-frame (but I believe I am medium-framed).


chuck May 4, 2011 at 6:15 pm

1) What does the Stephen think of the recent criticism of Gary Taubes’ data?

2) A new trend is emerging that drinking milk isn’t do any favors for osteoporosis. Thoughts?

2) Aside from fiber and possibly beta-glucan, what role can legumes have in a healthy diet?

3) Based on Stephen’s post on Polyphenols, what the opinion on getting too much antioxidants?

4) Do high-intensity workouts before breakfast followed by fasting have any merit?

5) Is juicing fruits (and vegetables) healthy, or are Jay Kordich/Jack Lalane insulin gifted? Any truth to the notion that you should not juice fruits and vegetables together?


Tyler B May 4, 2011 at 6:33 pm

With regard to the underlying biochemistry of leptin transport across the blood brain barrier, what do you think could be the mechanism by which factors like serum triglycerides can reduce maximum transport rate and result in leptin resistance? Is it known if the receptor regulation itself is being changed, binding to the receptors being blocked, or clathrin-coated pit formation being altered?

It seems confusing to me, since many factors (triglycerides especially) seem to actually raise transport rate for other proteins (like insulin) which rely on a similar mechanism (clathrin-coated pit transcytosis).

This is a purely scientific question, but I think the answer might shed some light on why/how certain diet and lifestyle interventions seem to reverse leptin resistance, and increase the chances of doctors prescribing these interventions.


KD May 4, 2011 at 7:45 pm

Since there seems to be increasing evidence that a lot of weight regulation is hormonal, is there anything in the paleosphere currently being recommended for fat loss that could actually discourage fat loss in women (pre-menopausal, 20s-30s, to be specific)? Much of what I’ve read seems to be targeted toward men and increasing or maintaining testosterone. Is there any known differences in the way gut bacteria affect women versus men, or any difference in macro-nutrient ratios that may work better for one sex over the other?

Much appreciated, fantastic podcasts so far!!


Lori May 4, 2011 at 8:17 pm

There is a lot of talk out in the blog world about avoiding PUFAs in all forms. Is there a big difference in PUFAs in whole nuts versus industrial seed oils and their effect on the body and losing weight/inflammation?


Vivian May 4, 2011 at 9:18 pm

Hi Stephan and Chris!
Thanks for the podcast -fascinating discussion.
How do we know when we’re too fat or not fat enough?
Is there a way to tell how much fat we should eat in, say, a day?


Suzan Robertson May 5, 2011 at 7:57 am

Chris, I listened to the first podcast. Can Stephen be a bit more specific/practical in describing an optimal plan for weight loss? The information he gave was at the very end of the podcast, and it was rather general. In addition, he mentioned on the podcast about people who aren’t losing weight may be wavering from strict adherence. Well, that doesn’t apply to many post-menopausal woman whom I’ve come across on blogs and forums who are faithfully sticking to Paleo/Primal, and still have a very difficult time losing weight, so can he address this issue? Thank you!


Maggie May 5, 2011 at 2:18 pm

I’d like to hear more about the role of malnutrition in obesity.


Ron May 5, 2011 at 6:20 pm


I recently discovered Dr. Art Ayers Cooling Inflammation blogsite and noticed you also were a reader. In one of his blogs where he wrote about biofilms, he said that “the biofilm matrix is like jelly, a gel formed by acid polysaccharide, pectin, cross-linked with calcium, and there is a reservoir of bacteria in gut biofilms. Inflammatory gut biofilms support system-wide chronic inflammation that leads to allergies, autoimmune diseases, degenerative diseases and probably cancers. Absorption problems (of nutrients) are likely.” In another blog I think he inferred (not quite sure) that constipation is one of the consequences of gut biofilms.

Now jump to the book ‘Breaking the Vicious Cycle’, written by the late Elaine Gottschall. The book discusses the cycle of events occurring in the intestines of those with digestive disorders and how the Specific Carbohydrate Diet (SCD) can break this cycle. She writes “the increasing levels of irritating substances given off by the growing microbial population cause intestinal cells to defend themselves. Mucus-producing cells (goblet cells), which are normally present in the intestine secrete their product to cover and protect the naked free surface of the intestinal absorptive cells. The small intestine responds to a disruption of the normal balance by producing more goblet cells which produce more intestinal mucus. As the integrity of the small intestine is further threatened by the microbial invasion and the products it produces, a thick mucus barrier forms for self defense. The enzymes embedded in the absorptive cell membranes cannot do the job for which they were designed: to make contact with and split certain sugars in the diet.” One of the consequences of this condition is loose stools or diarrhea.

Art recommends ingesting specific foods and supplements to break up the biofilm matrix. Elaine recommends that the carbohydrates consumed should be only those which are monosaccharides (fruits, honey, some veggies) and avoid disaccharides (sucrose) and polysaccharides (starches). She says that the digestive system can better fully digest the monosaccharides, thus not feeding the microbial population with undigested sugars and starches.

Do you think Art and Elaine are referring to the same condition? Do you think that the biofilm matrix Art refers to is formed by the polysaccharides that Elaine recommends avoiding? Any insight you can provide would be greatly appreciated.

All my best. Ron


Long Term LC Dieter May 5, 2011 at 11:23 pm

Regarding PUFAs, I have read some paleo bloggers recommend against fish oils or eating oily fish now. I have found lists of the PUFA content of common paleo foods floating around the internet! Is this really something to worry about?


Kerrick May 6, 2011 at 1:12 am

I’m interested—and maybe this isn’t the podcast to address it—in understanding more about this study associating high blood DHA levels with increased risk of aggressive prostate cancer: It’s just one study—actually a review of existing research—but it would be interesting to know what caused this particular correlation to show up in the data set.


sam May 6, 2011 at 8:29 am

Experienced 30lb. weight gain during a period (3 months) of unavoidable stress, despite eating less than normal. Realize now (23 yrs later) that it was cortisol related – so what can one do during times like these to avoid weight gain – is intense exercise the only option? and what if you are unable to do that?


Alex May 6, 2011 at 9:47 am

Both your blogs are such valuable resources. Thanks for all the good research and good writing. I suspect both of you are admirers of Gary Taubes. And you both recommend Anthony Colpo’s Cholesterol Con book. Yet Colpo has no respect for Taubes. See this, where he says:
What do I think of Taubes?

I think a lot of what he writes nowadays is complete and utter nonsense. And that’s putting it nicely….

Would love it if you could talk about this schism between Colpo and Taubes. Thanks


Tony May 6, 2011 at 6:23 pm

I would like to know his thoughts on the recent published research concerning DHA/fish oil supplements, Omega 3, etc and potential health concerns about supplementation with same.



Bryan Stell May 7, 2011 at 12:50 am

Fructose: I am a bit confused as to fructose metabolism. I believe it is similar to ethanol metabolism. Could we elaborate on the reasons behind this fructose alarmism. Is fructose from fruit metabolized the same as high fructose corn syrup. Lalonde And Wolf both are low on fructose thus fruit right now. Does eating a banana post workout do anything to restore my muscle glycogen? Also, this visceral fat around the waste and organs, is this a spill over from excess liver carbs mainly fructose? If you eat tons of animal fat to the point where you have over eaten and gain fat would it deposit in more of an apple shape, as in from neck to toe vs the pear shape?


Chris Kresser May 7, 2011 at 8:53 am

The question is the ratio of fructose to glucose in a food. If fructose and glucose are in a roughly equal amount, fructose is well-absorbed and tolerated in moderate quantities (like in whole fruit). But in foods that have excess amounts of fructose in relation to glucose, like HFCS (55% fructose) or agave syrup (90% fructose!), the fructose will be poorly absorbed. Excess fructose is toxic as Lustig and many others have pointed out. It raises uric acid, which in turn has many detrimental effects. Small amounts, fine. Large amounts, bad.


"Murph" Dillinger May 11, 2011 at 4:41 am

I’m a little bit confused here.

“But in foods that have excess amounts of fructose in relation to glucose”. I presume you are talking about ratio here ?

I can’t imagine 0.2 points ratio wise making a diffrence between OK and bad.

Honey (fructose/glucose) 50/44 ; 1: 1.13
HCFS (fructose/glucose) 55/41 ; 1: 1.34


Ron May 8, 2011 at 7:04 am

Chris: I listened to your first podcast with Stephan. Other than sauerkraut and j.artichokes, what are some other fermentable fibers? Thanks


Ron May 8, 2011 at 7:16 am

Chris: a follow up to this question. When you refer to fermentable, do you mean that the fermentation takes place naturally in the gut (except sauerkraut which is already fermented), or that the fiber can be fermented prior to ingestion? Thanks


Mitch Fletcher May 9, 2011 at 5:23 am

Dear Chris and Stephan,
I am interested in the relationship between the body fat setpoint and highly rewarding foods. Is there much evidence indicating that the rewarding property of highly palatable foods relies on the accompanying calories, or is it independent and can non-caloric sweeteners therefore raise the body fat setpoint just as effectively, for example?Many thanks,


Jennifer May 9, 2011 at 8:55 am

Would Stephan comment on the physiological state that makes a person plateau or stall when losing weight? I read a lot about “how you break a stall” which seems to come down to changing things in exercise or diet, but I’m really interested in what happens in the body to cause it in the first place.



Thalin May 9, 2011 at 11:09 am

Hi, I just recently discovered your blog and I am really interested in what you have to say about leptin resistance and body fat setpoint.

I have been obese long before turning 1. Later in life, mostly by NOT following doctors’ advice, I managed to lose a significant amount of fat, but I am still overweight…I’d love to lose another 20-30 pounds but my body seems to be against it, even if I eat 100% clean (I have been LCHF, 100% compliant Paleo for the last 2 years (80% for another 2 years prior to that), olympic weightlifter, crossfitter, etc…)

I think that my initial obesity was due to the fact that I was fed cow milk since day 1, which triggered inflammation, then insulin resistance and so on…
Do you think that could have triggered leptin resistance too? how do you measure it? is it reversible in the same way insulin resistance is? Does food palatability include…ehm…coffee (it’s the ONLY thing I can’t seem to be able to get rid of!).


Alex May 10, 2011 at 9:49 am

Chris Masterjohn has discussed the limitations of the following study ( in his post, “Gluten Sensitivity — Promises And Problems” due to the deamidated gluten used by the researchers. He explains that gluten is typically only rendered immunoreactive after it has been deamidated by the transglutaminase present from gut damage in celiacs. Stephan commented in a later Masterjohn post (“How to Properly Interpret Ex Vivo Studies”) that commercially baked goods often use deamidated gluten to improve baking properties. In addition, transglutaminase itself is also being used in processed food to modify the properties of meats and other products (there is even an Iron Chef episode featuring Chef Wylie Durfresne whose makes extensive use of transglutaminase in his style of cooking).

All this makes me wonder if the observation that gluten in wheat causes negative health outcomes in many people may be hugely confounded by processes used in the modern food system.

Do you think it’s possible that the problems related to wheat consumption result solely from a combination of plant breeding to increase gluten, modern food processing techniques, and industrialized food as a whole or is wheat simply inherently toxic? For example, if someone is consuming wheat along with a food product made using transglutaminase, could this be a potential cause of immune system reactions to gluten? Aside from being a waste of time, will properly preparing emmer or einkorn make it a relatively safe food?


Razwell May 10, 2011 at 11:55 am

Please ask Stephan if scientists have learned more about the chemical behavior of fat cell receptors.


Peter May 11, 2011 at 6:00 pm

Please outline a unified theory of obesity. Current (incomplete) theories are extremely unhelpful, particularly for those struggling with serious weight problems.


Jordan May 12, 2011 at 8:00 am

I am interested in research/studies/data related to cortisol’s effect on weight. I have spent (admittedly not a ton of) time looking, but am only seeing anecdotal information and advice to get more sleep, meditate, etc, etc. I would like to learn more about any relationship between cortisol levels and weight loss that is based on data.


Chris Kresser May 12, 2011 at 8:57 am

I suggest you check out The Cortisol Connection by Shawn Talbott. Tons of data in there supporting cortisol’s role in obesity and metabolic dysfunction.


Jonathan May 16, 2011 at 4:54 am

I’d love to hear your thoughts on vitamins A, D, K2-MK4, their interactions, and Dr. Weston Price’s work.


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