Another penny drops: Why severe hyperinsulinamia can occur with a small increase in exogenous carbohydrate intake.

This blog post is a result of Vim's comments in the previous blog post. A penny suddenly dropped!

From http://bja.oxfordjournals.org/content/85/1/69.full

Insulin has a Chalonic (inhibitory) action on blood glucose level (via the liver, muscle mass & fat mass), blood FFA level (via fat mass) and blood ketone body level (via the liver).

As mentioned in the comments, GHB has a stimulant effect - up to a certain level of blood GHB. Beyond that level, there's a powerful sedative effect. This is because at low levels of exogenous ketone body input, insulin secretion increases slightly to reduce hepatic ketogenesis.

At a certain level of exogenous ketone body input, hepatic ketogenesis falls to zero and cannot be reduced any further. Any slight increase beyond this point in exogenous ketone body input, results in a large increase in insulin secretion, as the pancreas increases Ketone body-Stimulated Insulin Secretion to maximum in a (failed) attempt to reduce blood ketone body level.

Exactly the same thing happens with exogenous carbohydrate or BHB input.

At a certain level of exogenous carbohydrate input, hepatic glucogenesis falls to zero and cannot be reduced any further. Any slight increase beyond this point in exogenous carbohydrate input, results in a large increase in insulin secretion, as the pancreas increases Glucose-Stimulated Insulin Secretion to maximum in a (failed) attempt to reduce blood glucose level.

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.

When bad science goes...pretty much the same!

After the previous post, you may have got the impression that things are getting worse. Hmmm!

From http://covermyfb.com/covers/27316/say%2Csee+and+hear+no+evil

Hat-tip to James Beckerman, MD for https://twitter.com/jamesbeckerman/status/507544419847786496, which refers to Comparison of Named Diet Programs Finds Little Difference in Weight Loss Outcomes.

This study comes to the opposite conclusion of the study in my previous blog post. As that study was a pile of poo, that must mean that this study is 100% correct, right? Hmmm!

Your enemy's enemy is not necessarily your friend. See What about the Other Weight Loss Diet Study??
"Previous meta-analyses, such as Hession et al, had balanced inclusion criteria that allow us to directly compare low-fat to low-carb diets.  They reported exactly what anyone would expect who is familiar with the weight loss diet literature:

1. At 6 months, low-carb diets consistently lead to greater weight loss than low-fat diets. 
2. At one year, the difference has all but disappeared. 
3. Neither diet produces particularly impressive weight loss at one year or more.
4. The weight loss effectiveness of typical low-fat diets tends to be modest at all time points.

Oh, well. It could have been a lot worse!
 

When good science goes bad, part n+1.

In When good science goes bad , I looked at the effect of funding bias on research.

From https://www.youtube.com/watch?v=sJ5jbxMjexo

Effects of Low-Carbohydrate and Low-Fat Diets: A Randomized Trial has just been published. As expected, low-carbers are positively creaming themselves over it. I instantly smelled a rat, as the full study was behind a pay-wall.

Remembering Krauss' shenanigans with "carbohydrate", consisting of 50% sugars + 50% "complex" carbs (maltodextrin & amylopectin are complex carbs that hydrolyse into glucose so rapidly that they have a GI of 100 on the "Glucose=100" scale.), I suspected dodgy carbs in the "Low-fat" group.

Luckily, David L. Katz, MD, MPH, FACPM, FACP had read the full study, and wrote about it in Diet Research, Stuck in the Stone Age.

As I suspected, it was another "fix-up" job, rigged to make low-carb diets look good, and low-fat diets look bad.

See also:-
Low-carbohydrate vs. Low-fat diets for Weight Loss: New Evidence,
What I Learned By Actually Reading That Low-Carb Is Best Study,
Is low-carb really the best weight loss diet? and
A Question about the latest diet study ...

The Minimally-Processed Whole-Food Plant-Based Diet.

It looks something like this:-

From http://littlesttumor.blogspot.co.uk/2012/02/whole-food-plant-based-diet-challenge.html

The commenter Melanie McSmiley reduced her weight by 45% using something very much like the above diet, and didn't suffer from any horrible side-effects such as Metabolic Shut-down. Well done, Melanie!

Here's an interesting talk by Denise Minger, which contains some big surprises:-

Wheat, Constipation, Ischaemic Heart Disease, Type 1 Diabetes, Schizophrenia and Autism.

Did you see this coming?

Gliadorphin 7, from http://en.wikipedia.org/wiki/Gliadorphin

The above 7-peptide chain contains 3 molecules of proline (the pentagon with a "N" at one corner), just like:-

Bovine β-casomorphin 7, from http://en.wikipedia.org/wiki/Casomorphin

From Further research for consideration in 'the A2 milk case'.
"Prior to discussion it must be clarified that the hypothetical link between A1 consumption with autistic spectral disorder (ASD) and schizophrenia relates not to the cause of the condition but to the aggravation of symptoms associated with these neurological conditions. More specifically, the hypothesis states that the absorption of food-derived exomorphins such as beta casomorphin 7 (BCM 7) may aggravate symptoms associated with ASD or schizophrenia.

This hypothesis is the basis of 'dietary intervention' that excludes gluten and casein (Knivsberg et al., 2002) from the diet of ASD patients. The former, gluten, has been shown to release gliadamorphin, an exomorphin comparable in opioid activity to BCM-7. A number of laboratories in the United States and Europe offer urine tests, which determine the level of peptides including BCM 7 and other beta casomorphins to serve as an indication of the potential usefulness of dietary intervention in the treatment of ASD patients. One published study reports that a casein- and gluten-free diet was accompanied by improvement in 81% of autistic children within 3 months (Cade et al., 2000)."


According to What is gliadorphin?
"What is gliadorphin? Gliadorphin (also called alpha-gliadin or gluteomorphin) is a substance that resembles morphine. Ordinarily, this is a short-lived by-product from the digestion of gluten molecules (found in wheat, barley, rye, oats, and several other grains). Gliadorphin is very similar to casomorphin. Gliadorphin has been verified by mass spectrometry techniques to be present in unusual quantities in urine samples of children with autism, and are believed by many to be a central part of the system of causes and effects that cause autistic development. The most probable reasons for the presence of these molecules are:
* One or more errors in the breakdown (digestion) process caused by enzyme deficiency and/or
* Abnormal permeability of the gut wall (that would allow these relatively large molecules to enter the bloodstream from the intestine in abnormal quantities)."

Continued on Rheumatoid Arthritis: It's the food!

Cow's milk, Schizophrenia and Autism.

As a result of comments to my previous blog post, I did a bit of digging. I dug up something.

From http://en.wikipedia.org/wiki/Milk

Stella Barbone linked to The A2 milk case: a critical review.

This was refuted by A critique of Truswell's A2 milk review.

That referenced Autism and schizophrenia: Intestinal disorders , Can the pathophysiology of autism be explained by the nature of discovered urine peptides? , Enzymatic release of neocasomorphin and beta-casomorphin from bovine beta-casein. & Opioid activities of human b-casomorphin.

Babies have naturally-high gut permeability, so wrong milk proteins may cause damage. Human breast milk contains only A2 casein.

In older humans, gut permeability is modulated by several factors.

1. Insufficient sun exposure, causing hypovitaminosis D. See http://www.ncbi.nlm.nih.gov/pubmed/?term=%22Vitamin+D%22[All+Fields]+AND+%22tight%20junction%22+AND+hasabstract[text]

2. Excessive consumption of oils high in polyunsaturated fatty acids. See Dietary Fat Can Modulate Intestinal Tight Junction Integrity.

3. Excessive consumption of Wheat. See http://www.ncbi.nlm.nih.gov/pubmed/?term=%22Wheat%22[All+Fields]+AND+%22tight+junction%22+AND+hasabstract[text]

4. Excessive exercise. See Shedding Some Light on the Leaky Gut <> Exercise Connection. Plus: 20+ Things You Should or Shouldn't Do to Protect and Restore the Integrity of Your Intestinal Wall.

5. Lack of dietary Sulphur. See Sulphation and Autism: What are the links? A good source of sulphate is Epsom Salts.

See also Physiology and Immunology of Digestion.

Continued on Wheat, Constipation, Ischaemic Heart Disease, Type 1 Diabetes, Schizophrenia and Autism.