Interview with Dr. Lagakos

Dr. Lagako's blog covers many of these topics in depth with citations to sientific research. I suggest reading some of his latest articles on the relationship between urine and blood ketone values in regards to circadian rythms and also his article on gelatin . http://caloriesproper.com/

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Here is a summary transcript of the interview:

0:00 In your book you describe several situations in which a calorie is not a calorie. I found the discussion of HGH particularly fascinating, yet you do not recommend it as a fat loss supplement. Why not?

A group of patients take HGH and regardless of the amount of calories it favorably affected nutrient partitioning. More calories went into building muscle and less into storing fat. The example was used to demonstrate that nutrient partitioning is very important and mediated by hormones. HGH has a lot of use in treating conditions but may not be good for those that are already healthy and already engaging in regular exercise. High intensity exercise is a known stimulus for natural HGH. Adding HGH might not add extra benefit. There are not many studies on athletes. Just stick with high intensity exercise until more research is done on athletes.

2:02  It appears that Nicotine has similar body re composition properties as HGH although perhaps it works on different pathways. Any thoughts on using nicotine patches as a fat loss aid?

Nicotine would be a vitamin if it were not addictive. It does have a lot of beneficial effects on cognition. It is a potent anti inflammatory agent. It improves insulin sensitivity. The strongest aspect is its ability to help attenuate appetite especially in those that are overweight. It might not work as well in an athlete except in improving cognition. It may help prevent post exercise soreness. Tobacco products decrease insulin sensitivity but nicotine by itself does not.

4:20 If you are already eating a ketogenic diet is there any reason to further control blood glucose.

No insulin sensitizing agents are useless to ketogenic dieters. If you are not being exposed to dietary carbohydrates then you have little need for a high level of insulin sensitivity. If you are adapted to a ketogenic diet you insulin sensitivity may decline a bit but that doesn't matter because you don't have insulin spikes without carbohydrates. Berberine, cinnamon, and bitter melon might have benefits reducing oxidative stress but they when it comes to the ability of managing blood glucose levels it doesn't matter to low carb keto dieters.

5:51 What is the mechanism of the insulin sensitivity agents?

There are a couple different. Some work on the amylase enzymes to prevent the digestion others act at the insulin receptor to dispose of the carbohydrates faster. There is a wide spectrum of mechanisms.

6:20 You push a lot of protein in your book. There is a big concern about too much protein kicking you out of ketosis. Is there a use for the blood sugar controls to prevent this?

These are two different issues. Consuming too much protein will not raise blood blood glucose levels. When you eat protein above your minimum requirements amino oxidation will occur in the liver in preference to fatty acid oxidation, which is the main method of ketone production. Also liver glycogen stores will increase decreasing the bodies need to oxidize fatty acids.

8:00 There is discussion by doctors that if you don't have more than 15 or 20 grams of protein in a single serving the amino acids will get used by the gut lining instead of going into the blood stream.

I don't believe that is true. If you have a lower protein intake the body will try to capitalize on it more efficiently by increasing protein synthesis. The gut does use certain amino acids. Most ingested glutamine will be metabolized in the intestine. Very little of the branch chain will bypass the liver and the intestine and go strait to the skeletal muscle. Other amino acids will be metabolized by the liver.

9:55 If you have all of your protein in one sitting you might stimulate excess amino acid oxidation so it might be better to have two meals of protein instead of one meal. Do you want 10 meals of protein, probably not.

10:20 What about large amounts of protein causing aging.

Protein may stimulate cell turnover and cell growth. When it comes to protein quality in the diet not sure how much high protein effects longevity. Virtually no human studies on the issue.

12:10 You pose a hypothesis our lifespan might be determined by the total calories consumed. Does eating amino acids instead of protein avoid the calorie countdown.

Even the BCAA that are shuttled directly to the skeletal muscle have calories and energy.

13:50 What about cold thermometers revving up your metabolic engine and aging you faster?

I'm not an expert in this at all. You can increase your brown adipose tissue by doing it. Some athletes do it but the data is very mixed. Most studies use very different CT protocols and give very different results. It could be helpful but should not be giving a blanket endorsement.

15:10 Are you increasing the mitochondrial density by doing CT?

You could be. The response of the mitochondria to the cold is increase uncoupling which could cause some oxidative stress down the line. The ketogenic diet will increase the number, function, and quality of mitochondria. Especially after 3 months. You will no longer be tired, you can do high intensity workouts and have increased endurance. The primary mediator of that is the affect of the diet on the mitochondria. From an athletic perspective the keto adapted state is critically dependent on the mitochondrial response.

16:50 After keto adaptation it seems that the actual BHOB values don't matter as much to how you feel and perform. Is that because you are running directly off of free fatty acids.

You should still be using ketones for some things. Your brain will still be oxidizing ketones. The urine ketone strips are a little iffy. You should register above 1 mM if you've adapted. The best measure of adaptation is how you feel and perform.

18:40 Do you know of any other quantitative measurements?

The blood meters are pretty good. Urinary a distant second.

19:00 Deep ketosis?

The number one factor in the level of ketosis and how easy getting in is patient history. The duration you've been on the diet. It is a direct reflection of their mitochondrial performance.

20:20 Calorie math?

Probably more than 4 lbs of muscle has been formed in 1 month where 15 lbs were gained on a ketogenic diet. Water weight gained would be low because you are ketogenic. Being an ketogenic athlete does amazing things for nutrient partitioning.

21:40 What about salts after the transition period?

When you switch to low carb it involves abandoning industrial processed foods which have a lot of salts. Without the carbohydrates you don't have much insulin which means you waste body salts a bit. This is magnified in a ketogenic state.

23:02 Insulin is more fat promoting than muscle building.

If you infuse just a small amount of insulin cells will completely stop fatty acid utilization. This small amount of insulin is much smaller than the amount required to build muscle or store salts.

23:50 What about gut function and thyroid function.

Gut stuff isn't in the book. Gut biome thrives on carbohydrates which are absent on a ketogenic diet. This doesn't bode well for gut health. The patch for this is fermented foods like sauerkraut, pickles, kefier. If you experience gut problems, bloating or constipation you really should consider fermented foods.

26:44 I started on a resistant starch protocol from feedtheanimal blog. Take potato starch with the fermented foods as prebiotic. Mix the PS with MCT oil. If I don't have gut health issues no reason to do it?

If you don't have gut health issues don't supplement. Only needed if there is a concern.

28:07 Talking about thyroid. Carbohydrates are not necessary. If you have symptoms of hypothyroid it is because of energy deficit. Keto diets are notorious for spontaneous energy reduction. Adequate calories and fat with weight maintenance should not be experiencing thyroid issues.

30:20 The healing properties of ketones seems to be incredible. Ketone salts are very interesting.

I just did a blog post about that in a recent blog post. When you infuse ketones into cells there is a huge increase in power output. Ketones are a super fuel.

32:15 If you want to experiment with the ketogenic diet you have to go longer than a month. The first week is difficult and athletic performance will take a hit.

33:20 What about re-feeds?

Carb re-feeds are unnecessary aside from emotional or psychological support. If you are in an energy deficit for too long you might want to ensure you get adequate calories.

34:47 I've avoided libido issues by eating a lot every 14 days or so.

Females might experience amenorrhea and may not cycle which is a normal response to energy deprivation. There are a few intervention studies I've posted on my blog. Testosterone levels increase with saturated fat.

37:20 Do you follow the lipid issues with low carb diets?

Trigs go down with decreased carb intake.

39:10 I prefer zetia to statins for cholesterol lowering drugs. I think high HDL is most improtant.

My personal quest is to remove omega 6 from my diet.

40:00 The benefits of that alone are tremendous. These oils are usually oxidized before consumption. Raw nuts probably are not so bad. Its better to get rid of vegitable oils.

41:02 Have you heard the theory that omega 6 are pro inflation resolution?

The major mediators are going to be the omega 3 from fish. There have been cell and animal studies about omega 6 but I think it will be omega 3s. I don't see a need for omega 6 in the diet.

43:22 Saturated fat is quite resistant to oxidative stress, so it is a good way to reduce oxidative stress in the body.

43:40 May readers send you questions.

I'm on twitter at caloriesproper you can email me at drlagakos at gmail or you could go directly to the website and leave a comment.