Low-carbohydrate diets: Green flags and Red flags.

Fun with flags. But first, a poem!
Atkins Antidote
 
Eating low carbohydrate what threat that poses?
Do my friends think I’m suffering from halitosis?
I’ve got these sticks for measuring ketoacidosis
I’m taking supplements but I don’t know what the dose is

I’m trying hard to keep in a state of ketosis
I’m not sure what the right amount of weight to lose is
I’m sure I’ve put on a pound just through osmosis
Is eating this way risking osteoporosis?

Are my kidneys wrestling with metabolic acidosis?
My store of liver glycogen I don’t know how low is
Who knows what the glycemic load of oats is?
Does anyone know if I can eat samosas?

Ian Turnbull (whose poetry is better than his science!)

I do. The answer's "No!" :-D

From https://forum.nationstates.net/viewtopic.php?f=23&t=13567&start=8925

The Green flags... 

1. For a person with Insulin Resistance, an ad-libitum low-carb diet results in more weight loss than an ad-libitum high-carb diet.

See How low-carbohydrate diets result in more weight loss than high-carbohydrate diets for people with Insulin Resistance or Type 2 Diabetes , for an explanation.

2. For a person with Type 1 Diabetes Mellitus (T1DM), a lowish-slowish-carb (~150g/day) diet results in minimal disturbances to blood glucose levels and minimal bolus insulin doses.

See Diabetes: which are the safest carbohydrates? , to see which foods should comprise the ~150g/day.

3. For a person with LADA or MODY, see 2.

4. For a person with Type 2 Diabetes Mellitus (T2DM), a LCLF 600kcal/day Protein Sparing Modified Fast can normalise BG in 1 week and reverse T2DM in 8 weeks (provided there are sufficient surviving pancreatic beta-cells). See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3168743/
"After 1 week of restricted energy intake, fasting plasma glucose normalised in the diabetic group (from 9.2 ± 0.4 to 5.9 ± 0.4 mmol/l; p = 0.003)." and
"Maximal insulin response became supranormal at 8 weeks (1.37 ± 0.27 vs controls 1.15 ± 0.18 nmol min−1 m−2)."

After 8 weeks, the diet is gradually changed to a healthy balanced diet containing carbs.

See also https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(17)33102-1/fulltext and Roy Taylor - Reversing the irreversible: Type 2 diabetes and you. 4th Oct 2014

Compare the above results with the inferior results obtained in A Novel Intervention Including Individualized Nutritional Recommendations Reduces Hemoglobin A1c Level, Medication Use, and Weight in Type 2 Diabetes, which is 10 weeks of VLCVHF Nutritional Ketosis.


As Insulin Resistance is multi-factorial, ALL of the potential causes need to be addressed. Once this has been done, IR should be reversed, allowing restrictions on dietary carbohydrate intake to be lifted. See also Can supplements & exercise cure Type 2 diabetes?

The Red flags...

The low-carb diet is a temporary patch to ameliorate the symptoms of IR/IGT/Met Syn/T2D, a bit like replacing a blown fuse by sticking a nail in its place, to allow the house to function while you fix the problem by fitting a new fuse. Although a house functions with a nail instead of a fuse, it's not a good idea to spend the rest of your life without a fuse to protect the house from fire in the event of a short-circuit.

So, why do LCHF'ers want to spend the rest of their lives using a temporary patch to ameliorate the symptoms of their IR/IGT/Met Syn/T2D?

Long-term use of very-low-carb, very-high-fat, low protein diets (a.k.a. Nutritional Ketosis) is not recommended.

1. Cortisol and adrenaline levels increase due to insufficient glucose production from dietary protein, resulting in gradually-increasing fasting BG level. See How eating sugar & starch can lower your insulin needs and Survival of the Smartest (part 2) - Dr Diana Schwarzbein.

2. If you do too much high-intensity exercise, you may momentarily black-out, fall and hurt yourself. See "Funny turns": What they aren't and what they might be.

3. Insulin Resistance is bad and should be reversed, if at all possible. See Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?

4. T2D causes carbohydrate intolerance and fat intolerance, resulting in high postprandial BG and high postprandial TG. See Lifestyle Intervention Leading to Moderate Weight Loss Normalizes Postprandial Triacylglycerolemia Despite Persisting Obesity.

5. Dyseverythingaemia isn't fixed. See When the only tool in the box is a hammer.

6. High-fat diets with no energy deficit result in high postprandial TG & high LDL-c. Postprandial lipaemia & high LDL-c are atherogenic. See Ultra-high-fat (~80%) diets: The good, the bad and the ugly.

7. Permanently-high NEFA (a.k.a. FFA). See Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, very-low-carbohydrate diet.

This raises the RR for Sudden Cardiac Death.

This also depletes beta cells causing loss of the 1st phase insulin response. See Chronic Exposure to Free Fatty Acid Reduces Pancreatic b Cell Insulin Content by Increasing Basal Insulin Secretion That Is Not Compensated For by a Corresponding Increase in Proinsulin Biosynthesis Translation.

Loss of the 1st phase insulin response causes Impaired Glucose Tolerance (IGT). See β-Cell dysfunction vs insulin resistance in type 2 diabetes: the eternal “chicken and egg” question

IGT causes high postprandial blood glucose after eating incidental carbohydrates. This is Metabolic Inflexibility, which isn't good.

8. Natural selection increases the incidence of a genetic impairment in the Inuit which reduces ketosis, inferring that reduced ketosis is an evolutionary advantage. Watch Inuit genetics show us why evolution does not want us in constant ketosis.

That's all for now.

Fun with maths: How many grams of "X" does it take to achieve "Y" mmol/L of "X" in the blood?

There are ≤3 fuels in blood - Glucose, Palmitic acid (FFA) & Beta-HydroxyButyric acid (Ketone body).

From http://www.medbio.info/horn/time%203-4/homeostasis1.htm#Sources%20of%20blood%20glucose:

Taking blood volume as 5L (a petite woman has less):-

5mmol/L of Glucose ≡ 4.5g of Glucose.

1mmol/L of Palmitic acid ≡ 1.28g of Palmitic acid.

6mmol/L of Beta-HydroxyButyric acid ≡ 3.12g of Beta-HydroxyButyric acid.

Instead of going on a ketogenic diet (with all of the health hazards associated with it), why not just add Beta-HydroxyButyric acid to your drinks?

There's a problem. All metabolic fuels produce an insulin response (from functioning pancreatic beta cells) - this is one of the ways the level of each fuel is regulated in a NFB loop. Therefore, drinking more than 3.12g of BHB (more than 2.76mL) produces a large insulin response, which results in sleepiness. Ditto for GHB.

Ketogenic Diets and Sudden Cardiac Death.

Last night, thanks to comments on my previous post, I stumbled across The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism, then a Google search led me to Sudden Cardiac Death and Free Fatty Acids.

The following graph is Figure 1 from Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet.

Nice Insulin, shame about the FFAs.

From the first link above:-
"Current ketogenic diets are all characterized by elevations of free fatty acids, which may lead to metabolic inefficiency by activation of the PPAR system and its associated uncoupling mitochondrial uncoupling proteins."

From the third link above:-
"Weight loss was similar between diets, but only the high-fat diet increased LDL-cholesterol concentrations. This effect was related to the lack of suppression of both fasting and 24-h FFAs."

See also Elevated plasma free fatty acids predict sudden cardiac death: a 6.85-year follow-up of 3315 patients after coronary angiography, and Circulating Nonesterified Fatty Acid Level as a Predictive Risk Factor for Sudden Death in the Population.

I think that's quite enough bad news for a Friday afternoon.


EDIT: So much for fat being a "clean-burning" fuel for the heart. Some people believe that, because dietary fats pass from the small intestine, via the Lacteals, to circulation at the Subclavian vein, this means that the heart prefers to burn fatty acids.

From Page 10 of HIGH CARBOHYDRATE DIETS: MALIGNED AND MISUNDERSTOOD:-

Human erythrocytes (red blood cells) contain cholesterol and it can contribute towards atherosclerosis. See https://twitter.com/Drlipid/status/496625195738619904.

See also Evidence for a cholesteryl ester donor activity of LDL particles during alimentary lipemia in normolipidemic subjects. This is more evidence that very high fat meals are atherogenic, which is relevant to Ultra-high-fat (~80%) diets: The good, the bad and the ugly.

Metabolic Inflexibility: What it really means.

Here's a picture from Metabolic Flexibility and Insulin Resistance.

The Metabolically-Inflexible (MI) & Insulin Resistance

Here's another picture.

Fig 2. ● = Metabolically-Flexible (MF). ○ = Metabolically-Inflexible (MI).

Salient points:
1) Excessively high serum FFA a.k.a. NEFA is bad.
2) Respiratory Quotient (RQ) a.k.a. Respiratory Exchange Ratio (RER) changes due to dietary changes are more sluggish in the MI than in the MF.
3) Under Insulin Clamp conditions, RQ/RER is lower in the MI than in the MF, due to impairment of glucose oxidation and non-oxidative glucose disposal.

I have posted this because of Danny Roddy's post Is Supplemental Magnesium A Surrogate For Thyroid Hormone? , which leads onto A Bioenergetic View of High-Fat Diets.

In the first article, Danny Roddy writes:-
"Additionally, taking magnesium while actively engaging in a diet or lifestyle that reduces the respiratory quotient (e.g., high-fat diet, light deficiency, excessive exercise) seems pretty silly. For example, as a rule, diabetics have a reduced respiratory quotient (Simonson DC, et al. 1988), tend to have higher levels of free fatty acids or NEFA (Kahn SE, 2006), and are often deficient in magnesium (De Valk HW, 1999)."

The second sentence (diabetics have a reduced respiratory quotient...and are often deficient in magnesium) seems to contradict the first sentence (...taking magnesium while actively engaging in a diet or lifestyle that reduces the respiratory quotient seems pretty silly).

Simonson DC, et al. 1988 is Oxidative and non-oxidative glucose metabolism in non-obese type 2 (non-insulin-dependent) diabetic patients.
"In conclusion, during the postabsorptive state and under conditions of euglycaemic hyperinsulinaemia, impairment of glucose oxidation and non-oxidative glucose disposal both contribute to the insulin resistance observed in normal weight Type 2 diabetic patients. Since lipid oxidation was normal in this group of diabetic patients, excessive non-esterified fatty acid oxidation cannot explain the defects in glucose disposal."

Impaired glucose oxidation with normal lipid oxidation lowers RQ/RER. Therefore, lower RQ/RER must be bad, right? Wrong. From the above study:-
"...euglycaemic insulin clamp studies were performed..."
Remember Salient point 3)? Simonson DC, et al. 1988 is an insulin clamp study, the results of which don't apply to free-living people (who aren't insulin clamped).

See also Determinants of the variability in respiratory exchange ratio at rest and during exercise in trained athletes. RER/RQ increases & decreases with increases & decreases in exercise intensity. This is Metabolic Flexibility (MF). Sorry, Danny.

Type 2 diabetes: your good signalling's gonna go bad.

A little bit of Tammy Wynette.

 

Good signalling:

There's a famine. You've got nothing to eat. Your body's glycogen stores have just run out. What happens next? As food intake is zero, serum insulin level is minimised, so lipolysis (fat mobilisation) is maximised. Serum NEFAs are maximised. High serum NEFAs provides fuel for tissues that utilise NEFAs (e.g. skeletal muscle) and a "stop utilising glucose!" signal, in conjunction with low serum insulin.

High serum NEFAs and low serum insulin increase ketogenesis in the liver, to give the parts of the brain that can utilise ketones an alternative choice of fuel, to reduce glucose utilisation to a minimum. Ditto for nerves. Glucose utilisation must be minimised during a famine, as it's generated by the liver & kidneys from glucogenic amino acids, obtained from lean body mass (LBM) by hypercortisolaemia.

Gone bad:

You're a type 2 diabetic with a fat belly. For reasons that I don't fully understand (better blood supply? close proximity to liver?), belly fat deposits spew NEFAs into the blood at a much higher rate than arm, boobs, love-handles, bum & thigh fat deposits. On a very-low-carb diet (less than 50g/day carbs), serum insulin level is minimised, so lipolysis (fat mobilisation) is maximised. Serum NEFAs are maximised. High serum NEFAs provides fuel for tissues that utilise NEFAs (e.g. skeletal muscle) and a "stop utilising glucose!" signal, in conjunction with low serum insulin.

A type 2 diabetic with a fat belly has underlying insulin resistance, due to over-full muscle, adipose and/or liver cells (making the liver spew glucose into the blood at too fast a rate, and the muscles & adipocytes take it out of the blood at too slow a rate). The very-low-carb diet makes the underlying insulin resistance worse and high serum NEFAs in a milieu of caloric sufficiency or excess wreak havoc. Serum glucose level increases. Serum LDL-c level increases. Serum TG level increases. Serum just about everything level increases, except for serum HDL-c level, which decreases.

Type 2 diabetes: between a rock and a hard place.

About 85% of type 2 diabetics have excessive visceral adiposity (belly fat). This post is about them.

Which is better - the rock or the hard place?

 

1) The rock:

This is serum glucose. People with type 2 diabetes can measure their own serum glucose. Eating carbohydrates makes serum glucose increase, the rate of increase being proportional to the glycaemic index and the magnitude of the increase being proportional to the grams of carbs consumed. By limiting the intake of dietary carbohydrates, large spikes in serum glucose can be avoided. The occasional spike above 7.8mmol/L (140mg/dL) doesn't hurt. It's spending long periods of time above 7.8mmol/L that's harmful (by glycation).

A low-carb diet (~150g/day of carbohydrate) halves serum glucose fluctuations compared to a higher-carb diet (~300g/day of carbohydrate). A very-low-carb diet (~75g/day of carbohydrate) further halves serum glucose fluctuations compared to the low-carb diet. This seems like an improvement, at first glance.

2) The hard place:

This is the invisible "elephant in the room", as it's not measured by doctors and people with type 2 diabetes can't measure it themselves. It's serum Non-Esterified Fatty Acids, or NEFAs (a.k.a. Free Fatty Acids, or FFAs). Serum NEFAs are high when fasting and fall after eating foods that raise serum insulin (carbs & certain proteins). People with type 2 diabetes and excessive visceral fat (belly fat) have higher-than-normal serum NEFAs due to adipocyte insulin resistance (IR). See Insulin Resistance: Solutions to problems.

Just like with serum glucose, there's nothing wrong with serum NEFAs going up & down. It's chronically-high serum NEFAs that's harmful (except during periods of caloric restriction). See Showing posts sorted by relevance for query NEFA "type 2 diabetes" .

See Fig. 1 in Lack of suppression of circulating free fatty acids and hypercholesterolemia during weight loss on a high-fat, low-carbohydrate diet. On a very-low-carb (less than 50g/day carbs) diet that's not calorie-restricted, serum insulin remains low all of the time. To insulin-haters, that sounds like a good thing. Unfortunately, it means that there is no insulin spike to suppress serum NEFAs by shifting the balance of NEFAs going in/coming out of fat cells. Serum NEFAs stay high all of the time, which is harmful.

Therefore, people who have type 2 diabetes and excessive visceral fat and who are permanently on a very-low-carb diet that's not calorie-restricted are harming themselves.