Carbs or Fat Make Us Fat?

The question has been a long unsettled question of debate between the Low Carb and Low Fat diet adherents. Here’s a good article which provides some insight from world population data (The Rise of Obesity and How to Make It Stop).

As for keto, here’s a good article on Seven Common Keto Diet Myths. I agree with every one of these being a myth which sidetracks keto dieters.

Coffee and Blood Lipids

One of the things that keto folks sometimes notice is an increase in blood lipids on the keto diet. This may be in some part due to increased coffee consumption. I never used to drink coffee but I started drinking coffee on keto for extra energy.

Turns out there’s an associational study on the subject (Stensvold I1, Tverdal A, Foss OP. The effect of coffee on blood lipids and blood pressure. Results from a Norwegian cross-sectional study, men and women, 40-42 years. J Clin Epidemiol. 1989;42(9):877-84.).

The association between boiled and filter coffee consumption and levels of cholesterol, triglycerides and blood pressure was studied, including 14168 men and 14859 women. A total of 94% drank coffee, 55% of the men and 48% of the women drank more than 4 cups per day. The type of coffee consumed varied between the counties, from 11 to 49% boiled and 49 to 87% filter coffee. Serum cholesterol increased linearly with increasing coffee consumption, and most strongly for boiled coffee. Controlling for other variables gave, for boiled coffee, an 8% increase for men and 10% for women. For filter coffee drinkers the coffee dose-cholesterol association remained significant only for women. Triglycerides showed a negative association with coffee, significant after adjustment for other variables. This effect was stronger for filter than for boiled coffee in both sexes. For men and women drinking 1 cup of coffee or more, a significant negative association between both systolic and diastolic blood pressure and number of cups of filter coffee was found.

Not going to change my life but perhaps a talking point with my doctor if my numbers are high.

Here’s a good metanalysis of the same subject (Jee SH1, He J, Appel LJ, Whelton PK, Suh I, Klag MJ. Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials. Am J Epidemiol. 2001 Feb 15;153(4):353-62.).

Macronutrients and Satiety

Gabor Erdosi gave a great talk recently.

Gabor’s talk

One of the slides really ties things together for me. There’s a debate in the keto community over which macronutrient provides the most satiety. We all agree it is not carbohydrates. Some of us say it’s fat which most satisfies our hunger. Others say it’s protein. I tend towards the protein side of the question but have found it to still be an open issue.

Role of Hormones – Ghrelin and Leptin

The hunger hormone Ghrelin is the key to refeeding. Roughly speaking, if your Ghrelin goes below a baseline you are less hungry. If it goes above the baseline you are more hungry.

Ghrelin, as compared to leptin, controls short term hunger. From this paper (Klok MD1, Jakobsdottir S, Drent ML. The role of leptin and ghrelin in the regulation of food intake and body weight in humans: a review. Obes Rev. 2007 Jan;8(1):21-34.:

Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation.

Gabor cited a study which compared human’s Ghrelin response to the three macronutrients (Karen E. Foster-Schubert, Joost Overduin, Catherine E. Prudom, Jianhua Liu, Holly S. Callahan, Bruce D. Gaylinn, Michael O. Thorner, David E. Cummings; Acyl and Total Ghrelin Are Suppressed Strongly by Ingested Proteins, Weakly by Lipids, and Biphasically by Carbohydrates, The Journal of Clinical Endocrinology & Metabolism, Volume 93, Issue 5, 1 May 2008, Pages 1971–1979).

Here is the key graph from the study.

Let’s look at each of the three macronutrients and their effect on hunger via their impact on Ghrelin levels.

Carbohydrates

Carbohydrates provided the greatest drop in Ghrelin for the first 140 minutes. They also have a significantly bigger Area Under the Curve (AUC) during that period. After that the slope rises dramatically. By 240 minutes the graph shows Ghrelin crossing over the baseline and going above the baseline. The slope up is shown roughly in the red line below.

That’s why you feel hunger when you eat carbohydrates and why you want to eat again just a couple of hours later. For me this comes to mind:


It’s the slope of the line up that drives you to want to refeed.

Fat

They keto community is correct. Fat (lipid) does drop Ghrelin. It does a decent job since it stays below baseline for many hours. Here’s the rough area under the curve (AUC) for Ghrelin after eating fat during those hours.

This explains to me why some people feel that Bulletproof Coffee works for them. It helps them not be hungry for hours. Fat alone help you stay below baseline levels of Ghrelin.

Protein

Here’s where the paper answers the question asked in the opening paragraphs of this page. Which macronutrient provides the best depression of Ghrelin? Clearly protein wins the battle. Here’s the AUC for protein:

Protein vs Fat

Putting both Protein and Fat AUCs together something interesting becomes clear.

There’s nothing that fat does that protein doesn’t do even better for depressing Ghrelin levels. Particularly at several hours in. They both keep the Ghrelin levels below baseline but protein does it longer and deeper. Yes, you do get hungry again when you return to near baseline at 6 hours in.

The debate will continue in the keto community until people actually examine the science. It seems pretty clear that protein is a superior choice to fat when taken in isolation. Both together seem like a fine choice so on some level both sides are correct.

Bulletproof Coffee or Bacon and Eggs? Bacon and eggs for me, thanks.



Keto Rant – Unlimited Fat?


There are people in ketoland who have magical thinking about the diet. They believe that all of the extra fat they eat will get turned 100% into ketones and peed out as excess from their bodies. Should be really easy to falsify this view by eating excess fat and measuring ketone concentrations…

Truth is the body stores the fat you eat. If you burn it off that day then so be it. If you burn off more than that you lose weight. If you burn off less then that you gain weight. No magic even in ketoland. The calories created from ketone production are minuscule – maybe 10-20% of your daily intake. Enough to replace the glucose missing in the diet. Very little goes out as waste (breath and urine). The bit that goes out is due to the inefficiencies of the process which drop with time (hence the lack of color on pee sticks for many people).

Time Restricted Feeding

Here’s an interesting study on High Fat diets and Time Restricted Feeding (Sherman H1, Genzer Y, Cohen R, Chapnik N, Madar Z, Froy O. Timed high-fat diet resets circadian metabolism and prevents obesity. FASEB J. 2012 Aug;26(8):3493-502. doi: 10.1096/fj.12-208868. Epub 2012 May 16.). The study

…tested whether long-term (18 wk) clock resetting by RF can attenuate the disruptive effects of diet-induced obesity.

The study looked at:

Analyses included liver clock gene expression, locomotor activity, blood glucose, metabolic markers, lipids, and hormones around the circadian cycle for a more accurate assessment.

Geneticaly, the study claims that:

Compared with mice fed the HF diet ad libitum, the timed HF diet restored the expression phase of the clock genes Clock and Cry1 and phase-advanced Per1, Per2, Cry2, Bmal1, Rorα, and Rev-erbα.

As far as weight goes:

Although timed HF-diet-fed mice consumed the same amount of calories as ad libitum low-fat diet-fed mice, they showed 12% reduced body weight, 21% reduced cholesterol levels, and 1.4-fold increased insulin sensitivity.

So, against a low fat diet the high fat diet did well. So far nothing new from usual. But what the study was concerned with was the Time Restricted Feeding (Intermittent Fasting) aspect. And that’s where the TRF diet did very well.

Compared with the HF diet ad libitum, the timed HF diet led to 18% lower body weight, 30% decreased cholesterol levels, 10% reduced TNF-α levels, and 3.7-fold improved insulin sensitivity. Timed HF-diet-fed mice exhibited a better satiated and less stressed phenotype of 25% lower ghrelin and 53% lower corticosterone levels compared with mice fed the timed low-fat diet. Taken together, our findings suggest that timing can prevent obesity and rectify the harmful effects of a HF diet.

Interesting results.

Here’s a related paper which notes a second study (Timed High Fat Diet Resets Circadian Metabolism and Prevents Obesity).

By an odd coincidence, a similar paper was published in the FASEB J2 about a month later, but the second paper didn’t seem to be aware of the first paper’s publication and didn’t cite it. In fact, the authors of the second paper thought that their paper was the first to be published on the subject of time restricted feeding of a high fat diet. 

Here’s the second paper (Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S, Leblanc M, Chaix A, Joens M, Fitzpatrick JA, Ellisman MH, Panda S. Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab. 2012 Jun 6;15(6):848-60). Here’s that abstract:

While diet-induced obesity has been exclusively attributed to increased caloric intake from fat, animals fed a high-fat diet (HFD) ad libitum (ad lib) eat frequently throughout day and night, disrupting the normal feeding cycle. To test whether obesity and metabolic diseases result from HFD or disruption of metabolic cycles, we subjected mice to either ad lib or time-restricted feeding (tRF) of a HFD for 8 hr per day. Mice under tRF consume equivalent calories from HFD as those with ad lib access yet are protected against obesity, hyperinsulinemia, hepatic steatosis, and inflammation and have improved motor coordination. The tRF regimen improved CREB, mTOR, and AMPK pathway function and oscillations of the circadian clock and their target genes’ expression. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure. We demonstrate in mice that tRF regimen is a nonpharmacological strategy against obesity and associated diseases.

Sidenote

I was pointed to this by an article by Mark Hyman who claimed about the study that:

Note that the link is not to a human study but to the mouse study above. A tale of mice or men. Someone in a Facebook group pointed me to the study as proof that we can eat fat ad lib. LOL. Proves exactly the opposite.

Made the New York Times

With the bar so low on science reporting this article was a welcome sight (How a Low-Carb Diet Might Help You Maintain a Healthy Weight) particularly from the New York Times. Researcher David Ludwig and team did a pretty nice study this time aimed at using a low carb diet for weight maintenance. Of course being Dr Ludwig he was aiming to show a metabolic advantage to the Low Carb diet compared with other higher carb diets. And his results showed that advantage.

The study itself is (Ebbeling Cara B, Feldman Henry A, Klein Gloria L, Wong Julia M W, Bielak Lisa, Steltz Sarah K et al. Effects of a low carbohydrate diet on energy expenditure during weight loss maintenance: randomized trial BMJ 2018; 363 :k4583) (full pdf).

The study participants were:

164 adults aged 18-65 years with a body mass index of 25 or more

The goal of the study was to determine if the total body energy expenditure (commonly referred to as “metabolism”) was increased on the Lower Carb intervention:

The primary outcome was total energy expenditure, measured with doubly labeled water, by intention-to-treat analysis. Per protocol analysis included participants who maintained target weight loss, potentially providing a more precise effect estimate.

Secondary outcomes were resting energy expenditure, measures of physical activity, and levels of the metabolic hormones leptin and ghrelin.

In other words, does Low Carb help with weight maintenance?
Most of us have lost quite a bit of weight in our lifetimes and found that our bodies want to return to that previous weight – plus some weight in most cases. Everyone recognizes that it’s a lot harder to maintain a weight loss than to lose weight.

I really like that the study wasn’t about weight loss with the usual advantages in the low carb diets due to higher glycogen losses. When people refer to water weight they rarely understand the good part of that water weight is two-fold. One is less inflammation – which is a good thing. The other is that the water comes out due to glycogen stores dropping. There’s 3-4 grams of water bound up with every gram of glycogen. Losing the glycogen is important for getting to visceral fat, particularly in the liver and pancreas.

Back to the study… The study controlled the one variable which everyone claims is the sole reason low carb diets do better – protein. The claim is that when protein is held equal low carb diets don’t beat other diets. But this study held protein the same between the interventions:

During the test phase, high, moderate, and low carbohydrate diets varied in carbohydrate (60%, 40%, and 20% of total energy, respectively) and fat (20%, 40%, and 60%, respectively), with protein fixed at 20%

Even the lowest level of 20% is a reasonably low carbohydrate diet. It wasn’t the typical 5% of the ketogenic diet. Not only did the study control for protein, it also controlled for added sugar, saturated fat and sodium. Nice touch.

The relative amounts of added sugar (15% of total carbohydrate), saturated fat (35% of total fat), and sodium (3000 mg/2000 kcal) were held constant across diets. 

Caloric intakes were adjusted to compensate for people continuing to drop weight.

The study had sufficient statistical power to tease out small differences between the groups that previous studies could not resolve (presumably the pilot Kevin Hall study which could not resolve differences due to lack of power (some of the conflict is documented by Dr Ludwig here).

The target of 135 completers provided 80% power, with 5% type I error, to detect a difference of 237 kcal/d in total energy expenditure change between one diet group and the other two diet groups. 

The results showed an increase in energy expenditure as a function of carbohydrate restriction. 

The difference in total energy expenditure was 209 to 278 kcal/d or about 50 to 70 kcal/d increase for every 10% decrease in the contribution of carbohydrate to total energy intake (1 kcal=4.18 kJ=0.00418 MJ).

Dr Hall, I think the ball is now in your court (Previous study)…

Update 2018-11-19: Kevin Hall has critiqued the methodology of this study: Kevin D Hall, Juen Guo, Kong Y Chen, Rudolph L Leibel, Marc L Reitman, Michael Rosenbaum, Steven R. Smith, Eric Ravussin. Methodologic Issues in Doubly Labeled Water Measurements of Energy Expenditure During Very Low-Carbohydrate Diets. bioRxiv 403931.

DLW calculations failing to account for diet-specific energy imbalance effects on RQ erroneously suggest that very low carbohydrate diets substantially increase energy expenditure.

Update 2018-12-01: Kevin Hall is going down swinging on this subject. Here’s some of the continuing controversy (Author Response to Hall and Guo Regarding Data Reanalysis and Other Criticisms).

The RCT That Will Never Happen

Here’s the Randomized Control Trial that I really want to see.

Take a lot of Type 2 Diabetics with BMIs in the obese range. Split them into two groups who are pair matched. Start one of the groups on Low Carb / High Fat diet and leave the control group on their customary Standard American Diet (SAD). Treat all of them with the standard of care as it is at the time. Track them for 40 years and look at the outcomes. Don’t just track some of the benchmarks like LDL cholesterol. Track all of their results including all-cause mortality. 

It won’t happen for too many reasons. And it doesn’t take a belief in conspiracy theories to figure out why. Perhaps the biggest reason is nobody makes money with Low Carb/High Fat and a study with sufficient statistical power would be very expensive.

In the meanwhile, we are all n=1. And none of us have 40 years. And no point in looking for the RCT above since it’s never going to happen. It would have had to start before anyone knew the right questions to ask.

How Low to Go?

I’ve done somewhere around 50 grams of carbohydrates a day (30 grams when subtracting out fiber) for the past year. And my blood sugar control has been great. I’ve wondered how low someone has to go (or stay) in order to control Type 2 Diabetes. Certainly, the weight loss I’ve had (120 lbs) is a part of the solution. Being at a low body fat percentage now (7.5% per BodPod) has to help as well. My weight has been stable for 6 months now as well which means I’ve not lost or gained any weight – I was at 164.7 lbs when I took the BodPod test and today I weighed 163.7 lbs (close enough). My coffee consumption (which helps in weight loss for sure) is higher than ever before but I’m trying to keep the caffeine down by mixing in mostly decaf coffee. 

So all of this begs the question of how many grams of carbs I could tolerate. Now, I am not going to be testing this anytime soon. I find the advantages of being low carb just way too easy (see above for the results). I did find a study that might provide at least a partial answer to the question of how many grams of carbs can keep someone in remission from Diabetes.

The answer is in this 2009 study (Haimoto H, Sasakabe T, Wakai K, Umegaki H. Effects of a low-carbohydrate diet on glycemic control in outpatients with severe type 2 diabetes. Nutr Metab (Lond). 2009 May 6;6:21).

Now, I wouldn’t even call this diet at 30% of calories from carbohydrates a “Low Carbohydrate” by any definition that I would recognize but it has interesting results. One of the things that was interesting is that the study was done on severe diabetics (HbA1c levels of 9.0% or above). This is not a group of new diabetics nor were the participants young. They were a pretty good representative of Type 2 Diabetics with poor blood sugar control. The participants:

were instructed to follow a low-carbohydrate diet (1852 kcal; %CHO:fat:protein = 30:44:20) for 6 months in an outpatient clinic and were followed to assess their HbA1c levels, body mass index and doses of antidiabetic drugs.

The results were really good. Many of the participants got off their medications and:

HbA1c levels decreased sharply from a baseline of 10.9 ± 1.6% to 7.8 ± 1.5% at 3 months and to 7.4 ± 1.4% at 6 months.

These are similar to the results I got with the Low Carbohydrate diet when I got to an HbA1c level of 6.4. They are not as good as the results I got over the last couple of years with even lower levels of carbohydrates plus intermittent fasting.

In spite of being on a fairly low calorie diet (1852 kcal) they didn’t lose much weight. This group also didn’t seem to be all that obese since their BMI was around 24 (top end of “normal” weight).

Body mass index decreased slightly from baseline (23.8 ± 3.3) to 6months (23.5 ± 3.4).

So, if you are “normal” weight and diagnosed as diabetic then dropping from the Standard American Diet (SAD) 50% of calories from carbohydrates to 30% might give as good of control as exogenous Insulin without the long term increase in insulin resistance that comes along with Insulin therapy.

There was one telling outlier in the data.

One female patient had an increased physical activity level during the study period in spite of our instructions. However, her increase in physical activity was no more than one hour of walking per day, four days a week. She had implemented an 11%-carbohydrate diet without any anti-diabetic drug, and her HbA1c level decreased from 14.4% at baseline to 6.1% after 3 months and had been maintained at 5.5% after 6 months.