Historical perspectives on the impact of n-3 and n-6 nutrients on health, by Bill Lands.

Here's Fig. 1. from http://www.sciencedirect.com/science/article/pii/S0163782714000253

Relating tissue HUFA balance with blood cholesterol and heart attacks. Results from the 25-year follow-up in the Seven Countries Study [35] were discussed in an earlier review [10] which noted that “Food energy imbalances which elevate blood cholesterol may be fatal only to the degree that omega-6 (n-6) exceeds omega-3 (n-3) in tissue HUFA. Such evidence raises questions about the hypothesis that blood cholesterol levels cause CHD.” Northern Europe and Southern Europe have abbreviations “No.” and “So.”, respectively. The Figure is reprinted with permission of the publisher.

Hat-tip to Dr. Thomas Dayspring for Tweeting this review.

Fig. 1 is interesting, as it shows a significant association between 25-year CHD mortality and Serum Total Cholesterol for every region except Japan. What's different about Japan, compared to Northern Europe, USA, Serbia, Southern Europe & Crete?

According to Measuring Blood Fatty Acids as a Surrogate Indicator for Coronary Heart Disease Risk in Population Studies , Philippines & Iceland have lower % linoleic acid than Japan. Where's the CHD vs TC data?

Could another difference be that the Japanese eat rice, a relatively intact grain, instead of foods made from wheat grain dust (i.e. flour) as their main source of dietary carbohydrates?

See also Using 3–6 differences in essential fatty acids rather than 3/6 ratios gives useful food balance scores , and Omega 3-6 Balance Score.

Depression: The similarity between magnesium and ketamine in inducing amnesia for bad memories.

Here's a 2D-skeletal model of the ketamine molecule.

From http://commons.wikimedia.org/wiki/Main_Page

Thanks to Emily Deans for bringing Ketamine, magnesium and major depression – From pharmacology to pathophysiology and back to my attention some time ago, in a Tweet.

"The link to the pathophysiology of depression is not clear. An overlooked connection is the role of magnesium, which acts as physiological NMDA-receptor antagonist:

1. There is overlap between the actions of ketamine with that of high doses of magnesium in animal models, finally leading to synaptic sprouting.

2. Magnesium and ketamine lead to synaptic strengthening, as measured by an increase in slow wave sleep in humans.

3. Pathophysiological mechanisms, which have been identified as risk factors for depression, lead to a reduction of (intracellular) magnesium. These are neuroendocrine changes (increased cortisol and aldosterone) and diabetes mellitus as well as Mg²⁺ deficiency.

4. Patients with therapy refractory depression appear to have lower CNS Mg²⁺ levels in comparison to health controls.

5. Experimental Mg²⁺ depletion leads to depression and anxiety-like behavior in animal models.

6. Ketamine, directly or indirectly via non-NMDA glutamate receptor activation, acts to increase brain Mg²⁺ levels. Similar effects have been observed with other classes of antidepressants.

7. Depressed patients with low Mg²⁺ levels tend to be therapy refractory. Accordingly, administration of Mg²⁺ either alone or in combination with standard antidepressants acts synergistically on depression like behavior in animal models.

I'm wondering whether the amnesia for vivid dreams (if you wake up in the middle of one) is mediated by magnesium, as amnesia is a ketamine-like effect.

Therefore, a deficiency in magnesium may cause bad memories to linger, increasing the risk factor for situational depression.

4g/day of Epsom Salts provides 400mg/day of Magnesium. Dissolve the Epsom Salts in warm water and add the solution to your drinks over a 24 hour period, to maximise absorption & minimise laxation.

See also Ketamine, and Mechanisms underlying differential effectiveness of memantine and ketamine in rapid antidepressant responses.

Negative feedback loops, Tolerance, Dependence & Withdrawal.

I couldn't find the plot that I was looking for, but this electrical plot is equivalent.

From http://www.tpub.com/neets/book9/37k.htm

e_A represents the amount of a substance that perturbs one of the body's negative feedback loops. The amount oscillates between 0V & 100V.

e_R represents the effect of the substance on the body. 100V represents maximum effect and -100V represents maximum anti-effect.

The very first time that the substance is taken, there is 100V of effect, initially. As the time-constant of the negative feedback loop "kicks-in", the effect decays exponentially. Just before the substance is discontinued, the effect is down to 36.8V. Just after the substance is discontinued, the anti-effect is -63.2V. If the input continues to oscillate between 0V & 100V, the effect & anti-effect eventually become equal in magnitude. This is known as "cycling".

If the substance is applied continuously, the effect decays exponentially to 0V. When the substance is discontinued, the anti-effect is -100V initially, but decays exponentially to 0V.

This is analogous to drug tolerance, dependence & withdrawal, where eventually, the user has to take the drug just to feel normal, and discontinuing the drug gives the worst withdrawal symptoms ever, initially. After the drug has been discontinued for a while, the withdrawal symptoms decay exponentially to zero.

The above also applies to supplements that perturb one of the body's Hypothalamic Pituitary NFB loops e.g. the HPA (Adrenal), the HPG (Gonadal) or the HPT (Thyroid) Axes, or any other system (as everything in the body is regulated by a negative feedback loop).

This explains why a supplement can work really well at first, then its effect decays exponentially, until there is zero effect. The loop has compensated for it.

EDIT: If a loop is broken, due to zero secretion of one of the hormones controlling it, then a prescription drug/hormone restores the loop's output level to normal. E.g.

1) Prednisone for a broken HPAA (primary, secondary or tertiary hypoadrenalism) e.g. Addison's Disease.
2) Testosterone (men) or progesterone (women) for a broken HPGA (primary, secondary or tertiary hypogonadism).
3) Levothyroxine for a broken HPTA (primary, secondary or tertiary hypothyroidism) e.g. Hashimoto's thyroiditis.

I'm on 2) & 3), due to a broken pituitary gland. Luckily, it's not completely broken, so I don't need 1).

Nonequilibrium thermodynamics and energy efficiency in weight loss diets, by Richard D Feinman and Eugene J Fine.

From http://www.caloriegate.com/the-black-box/9-pictures-that-prove-beyond-a-reasonable-doubt-that-calories-dont-count

From Nonequilibrium thermodynamics and energy efficiency in weight loss diets:-

"Conclusion
Emphasis on kinetics and nonequilibrium thermodynamics provides a conceptual framework for understanding the effect of macronutrient composition on maintenance and change of body mass and possibly for analysis of adipocyte metabolism in general. The simple model presented is intended to be consistent with a general shift away from equilibrium thermodynamics and towards a more dynamic analysis of cellular processes."

Sounds plausible. There's only one thing wrong with Feinman et al's article - it's completely wrong!

Consider two rooms:-

Room "A" has an adjustable heater. The heater is adjusted until the room temperature is 20°C.

Room "B" has a radiator, controlled by a wall-stat set to 20°C. The radiator is on, and the room is at 20°C.

We have two rooms of the same size, at the same temperature.

If you plug in & turn on a 2kW fan heater in each room, what happens to the temperature in each room?

Room "A" gets warmer, because there is 2kW more heat power entering it.

Room "B" stays at 20°C, because the wall-stat reduces the heat power from the radiator by 2kW.

The human body stays at 37°C ±~2°C, because there's a Negative Feed-Back loop adjusting the heat power produced, via UCP's, futile cycles, thyroid hormones, shivering and heat conservation/wasting behaviours.

∴ Variable heat power generation due to variable Dietary Efficiency doesn't change E_out.

EDIT: By request, here's Figure 1 from the above study.

This suggests that fat mass & therefore weight can increase indefinitely - at maintenance energy intake, due to the effect of insulin on HSL. This, of course, is quite impossible!

From The Energy Balance Equation:-

Change in Body Stores = E_in (corr for digestion) - E_out (BMR/RMR + TEF + TEA + SPA/NEAT)
__BMR/RMR & TEA ∝ weight
∴ ↑ weight → ↑ E_out
__If E_in = constant, ↑ E_out → ↓ (E_in - E_out) → ↓ weight
∴ ↑ weight → ↓ weight
∴ Figure 1 is wrong.

The Ketogenic Diet: Uses in Epilepsy and Other Neurologic Illnesses.

Fools claim that I am anti-ketogenic diets. Am I ****! beta-Hydroxybutyric acid has its uses...

From http://www.fuelforthought.co/the-ketogenic-diet-uses-in-epilepsy-and-other-neurologic-illnesses-2/

From The Ketogenic Diet: Uses in Epilepsy and Other Neurologic Illnesses:-

"Inconsistencies in studies attempting to correlate seizure protection with levels of ketone bodies suggest that another mechanism may be involved in the diet’s beneficial effects on seizures. Several mechanisms have been proposed, including changes in ATP production making neurons more resilient in the face of metabolic demands during seizures; altered brain pH affecting neuronal excitability; direct inhibitory effects of ketone bodies or fatty acids on ion channels; and shifts in amino acid metabolism to favor the synthesis of the inhibitory neurotransmitter GABA."

GABA is an interesting neurotransmitter, as it's the chief inhibitory neurotransmitter in the mammalian central nervous system.

I know of two other substances that enhance GABA's effects - Alcohol and Benzodiazepines.


In conclusion:

I'm in favour of ketogenic diets under medical supervision, as therapy for neurologic conditions etc.

I'm not in favour of ketogenic diets under lay supervision, as a supposed aid for weight loss.

Dietary Carbohydrate restriction as the first approach in diabetes management. Critical review and evidence base, by Richard D Feinman et al.

Another Bookmarking post.

From http://dgeneralist.blogspot.co.uk/2013/11/the-low-carb-high-fat-diet.html

The study in question is Dietary Carbohydrate restriction as the first approach in diabetes management. Critical review and evidence base. Here are my comments on the 12 points.

Point 1 is wrong. For ~85% of people who have T2DM, hyper*emia is the salient feature, where * = glucose, TG's, cholesterol, NEFAs, uric acid etc. For ~85% of people who have T2DM, it's a disease of chronic excess.

Ad lib LCHF diet → ↓ Blood glucose & ↓ fasting TG's, but ↑ PP TG's, ↑ LDL-C, ↑ LDL-P & ↑ NEFAs. See Postprandial lipoprotein clearance in type 2 diabetes: fenofibrate effects.
↑ PP TG's is associated with ↑ RR of CHD.
↑ LDL-P is associated with ↑ RR of CHD.
↑ NEFAs are associated with ↑ RR of Sudden Cardiac Death.

Point 2: So?

Point 3 is wrong. A caloric deficit is essential, to reverse liver & pancreas ectopic fat accumulation. See Reversing type 2 diabetes, the lecture explaining T2D progression, and how to treat it.

Point 4 is misleading. Feinman doesn't distinguish between different types of carbohydrates. Starches, especially resistant starches (e.g. Amylose) are beneficial. See Point 11.

Point 5 is moot. Prof. Roy Taylor found that motivation determines adherence. Prof. Roy Taylor's PSMF was adhered to. See Point 3.

Point 6 is correct. Prof. Roy Taylor's PSMF is ~1g Protein/kg Bodyweight, some ω-6 & ω-3 EFAs & veggies for fibre. See Point 3.

Point 7 is misleading. Siri-Tarino et al gave a null result by including low fat studies, also a dairy fat study which had a RR < 1 for increasing intake. Chowdhury et al gave a null result, as some fats have a RR > 1 for increasing intake and some have a RR < 1 for increasing intake.

Point 8 is irrelevant. ↑ Dietary fat → ↑ 2-4 hour PP TG's. See Point 1.

Point 9 is partly correct. Microvascular, yes. Macrovascular, no. See Point 8.

Point 10 is mostly irrelevant. See Point 8.

Point 11 ignores results obtained with high-starch diets, where the starch contains a high proportion of Amylose. See Walter Kempner, MD – Founder of the Rice Diet and From Table to Able: Combating Disabling Diseases with Food.

Point 12 is misleading. The low-carbohydrate part is fine. It's the high-fat part that can cause problems. See Point 8.

Some thoughts on the essentiality of dietary carbohydrates.

I didn't know that there's a watch strap called Essentiality. I do, now.

From https://svpply.com/item/3229602/Swatch_Skin_Collection_Silver_Essentiality

This is a book-marking post for thoughts I had in https://www.facebook.com/TheFatEmperor/posts/1442430506020812.

"The human body does not need carbohydrates from an external food source, because it is capable of very precisely and correctly assembling its own amounts of glucose that is needed in very small amounts for auxiliary and specialized functions." - Igor Butorski.

1) It's not very precise. See http://nigeepoo.blogspot.co.uk/2012/04/how-eating-sugar-starch-can-lower-your.html

2) It's not enough to fuel high-intensity exercise. See http://nigeepoo.blogspot.co.uk/2011/02/funny-turns-what-they-arent-and-what.html

3) Using the above argument, the human body does not need saturated fats & monounsaturated fats from an external food source, because it is capable of very precisely and correctly assembling its own amounts of saturated fats & monounsaturated fats (out of carbohydrate) that are needed in very small amounts for auxiliary and specialized functions.

If we only consumed Essential Fatty Acids, Essential Amino Acids, Vitamins, Minerals, Fibre/Fiber, Water & Anutrients, there wouldn't be much to eat. Also, there wouldn't be a source of chemical energy to generate heat energy & mechanical energy. That's what dietary carbohydrates & fats are for.

Respiratory Exchange Ratio/Respiratory Quotient (RER/RQ) varies with carbohydrate & fat intake, as the body preferentially oxidises the fuel that's most readily available.

RER/RQ varies with Exercise Intensity.
Low-intensity exercise results in mostly fats being oxidised.
High-intensity exercise results in mostly carbohydrates being oxidised.
Medium-intensity exercise results in a mixture of fats & carbohydrates being oxidised.