This video from 1979 is still relevant to the problems of the world today. Too much. Too young.
14 Ağustos 2014 Perşembe
13 Ağustos 2014 Çarşamba
Dear ItsTheWoo, how do you do?
This post is attacking what I consider to be faulty reasoning. It's not a personal attack on ItsTheWoo, who I like (even though she drives me up the wall, sometimes!).
See What I believe and what I don't.
The basic The Energy Balance Equation:- Change in body stores = Ein - Eout
For a detailed mathematical analysis of weight change, see Completing the trine: vive la différence!
From Back to black, CIAB, pharmaceutical drug deficiencies & nerds:-
Where body weight is concerned, calories count (but don't bother trying to count them).
Where body composition is concerned, partitioning counts.
Where health is concerned, macronutrient ratios, EFAs, minerals, vitamins & lifestyles count.
The faulty reasoning is in Dear Nigel and other CICO zealots: you are ignorant. Charming!
I'll quote passages from it and refute them, one by one.
Calories determine weight change. See Bray et al shows that a calorie *is* a calorie (where weight change is concerned). It would have been nice if Fig. 6 had contained a plot of "Effect of energy intake on change in body weight", but it didn't.
LBM = Lean Body Mass
FM = Fat Mass = Body Fat
Weight change = LBM change + FM change
Weight change varies from ~+3.5kg (@ +2,500kJ/d) to ~+9.1kg (@ +5,900kJ/d).
(Maximum weight increase)/(minimum weight increase) = 2.6
(Maximum kJ/day increase)/(minimum kJ/day increase) = 2.36
∴ A calorie IS a calorie (where weight change is concerned).
∴ Insufficient protein can result in loss of LBM (bad).
The main thrust of ItsTheWoo's argument is that inter-personal variations in weight gain from subject to subject, invalidates Bray's conclusion. It doesn't.
Some subjects become more energetic on a 40% caloric surplus, which increases their NEAT & TEA, which increases their Eout, which reduces their weight gain.
Some subjects don't change their energy on a 40% caloric surplus, which doesn't change their NEAT & TEA, which results in intermediate weight gain.
Some subjects become less energetic on a 40% caloric surplus, which decreases their NEAT & TEA, which decreases their Eout, which increases their weight gain.
I believe that the Insulin Sensitivity (IS) of the subject determines which category they fall into and by how much. The higher the IS, the higher the energy, as high IS results in low serum insulin, which minimises sedation. Energy Balance always applies.
I've never stated that Calories exactly determine weight change. That's a strawman.
I've never stated that Calories determine body composition. That's a strawman.
Somewhere within all of the irrelevant waffle about rules & laws, ItsTheWoo raises an interesting point. Although a caloric surplus is always required for weight gain, eating more Calories can sometimes result in zero weight gain. How so? From ItsTheWoo's link:-
"Conclusion: This data is the first to demonstrate a resistance to weight gain in constitutional thinness (CT) population in response to 4-week fat overfeeding, associated with an increase in resting energy expenditure and an emphasised anorexigenic hormonal profile.
In CT people, their energy expenditure increases in line with their energy intake. Therefore, even though they're eating more Calories, there's no caloric surplus, therefore there's no weight gain. Energy Balance always applies.
Just because it is *impossible* for a reasonable free living human to quantify all of the metabolic, endocrine, nervous system factors influencing adipocyte growth changes does not mean they don't fucking exist."
ItsTheWoo left out my calculations. Here they are:-"if I eat 2000 calories of a ketogenic diet in 3 hrs, most of it is wasted as heat, physical energy (I know, because I am EXTREMELY warm/energetic) and then the rest of time i am using a relatively greater percent of stored fat."
Do you know at what rate you're burning-off extra energy intake as heat energy output when you're "EXTREMELY warm/energetic"? Here's an estimate:-
If the mean TEF for your meal is 11% (assuming your meal is 50%E protein & 50%E fat), that's 220kcals (921kJ) "wasted" as heat energy. That'll make you feel EXTREMELY warm, as 220kcal raises the temperature of 57kg of water (your body) by 3.84°C.
A 2,000kcal meal (a whole day's worth of food) takes a lot longer than 3 hours to digest & absorb. I'll guesstimate it as 24 hours. 921kJ of extra heat power over the course of 24 hours = 10.7W, which is an increase of 17.7% over your normal Metabolic Rate of ~60W heat power (~1kcal/minute).
It's easy to "prove" something by being vague. That's PSEUDOSCIENCE. I do science. If you do the maths, you can see that, of the 2,000kcal ketogenic meal, most of it isn't wasted as heat, because if most of it is wasted as heat, ItsTheWoo would spontaneously combust!
2) If atkins was wrong (you pee out all LCHF food) who cares? That was 30+ years ago. He was a cardiologist who observed a VLC diet made him slim. He used his medical education to hypothesize a reason why. His hypothesis was wrong, but his observations were right. This happens all the time in science or basic human reasoning; make observations, form hypothesis. The hypothesis may be wrong, the findings are STILL RIGHT (i.e. low carb diets DO make slim, just not via peeing away ketones)."
1) There is no Metabolic Advantage to ketogenic diets. See http://www.jbc.org/content/92/3/679.full.pdf
2) Atkins' observations were wrong. See The Battle of the Diets: Is Anyone Winning (At Losing?)
a) Low-Carb diets work better than High-Carb diets for people who are Insulin Resistant.
b) Low-Carb diets work worse than High-Carb diets for people who are Insulin Sensitive.
c) Low-Carb diets work the same as High-Carb diets for everybody in Metabolic Ward Studies.
If there's a Metabolic Advantage to ketogenic diets, they would work better than high-carb diets all the time. They don't. See How low-carbohydrate diets result in more weight loss than high-carbohydrate diets for people with Insulin Resistance or Type 2 Diabetes for my hypothesis, which explains a), b) and c).
 |
| From http://hypetrak.com/2011/10/mayer-hawthorne-how-do-you-do-full-album-stream/ |
See What I believe and what I don't.
The basic The Energy Balance Equation:- Change in body stores = Ein - Eout
For a detailed mathematical analysis of weight change, see Completing the trine: vive la différence!
From Back to black, CIAB, pharmaceutical drug deficiencies & nerds:-
Where body weight is concerned, calories count (but don't bother trying to count them).
Where body composition is concerned, partitioning counts.
Where health is concerned, macronutrient ratios, EFAs, minerals, vitamins & lifestyles count.
The faulty reasoning is in Dear Nigel and other CICO zealots: you are ignorant. Charming!
I'll quote passages from it and refute them, one by one.
- "With a zero caloric deficit, there is zero weight change"
Calories determine weight change. See Bray et al shows that a calorie *is* a calorie (where weight change is concerned). It would have been nice if Fig. 6 had contained a plot of "Effect of energy intake on change in body weight", but it didn't.
LBM = Lean Body Mass
FM = Fat Mass = Body Fat
Weight change = LBM change + FM change
Weight change varies from ~+3.5kg (@ +2,500kJ/d) to ~+9.1kg (@ +5,900kJ/d).
(Maximum weight increase)/(minimum weight increase) = 2.6
(Maximum kJ/day increase)/(minimum kJ/day increase) = 2.36
∴ A calorie IS a calorie (where weight change is concerned).
∴ Insufficient protein can result in loss of LBM (bad).
The main thrust of ItsTheWoo's argument is that inter-personal variations in weight gain from subject to subject, invalidates Bray's conclusion. It doesn't.
Some subjects become more energetic on a 40% caloric surplus, which increases their NEAT & TEA, which increases their Eout, which reduces their weight gain.
Some subjects don't change their energy on a 40% caloric surplus, which doesn't change their NEAT & TEA, which results in intermediate weight gain.
Some subjects become less energetic on a 40% caloric surplus, which decreases their NEAT & TEA, which decreases their Eout, which increases their weight gain.
I believe that the Insulin Sensitivity (IS) of the subject determines which category they fall into and by how much. The higher the IS, the higher the energy, as high IS results in low serum insulin, which minimises sedation. Energy Balance always applies.
I've never stated that Calories exactly determine weight change. That's a strawman.
I've never stated that Calories determine body composition. That's a strawman.
- " Every subject [in bray's overfeeding study] gained weight (mostly fat mass) during the 40% energy excess overfeeding period. "
Somewhere within all of the irrelevant waffle about rules & laws, ItsTheWoo raises an interesting point. Although a caloric surplus is always required for weight gain, eating more Calories can sometimes result in zero weight gain. How so? From ItsTheWoo's link:-
"Conclusion: This data is the first to demonstrate a resistance to weight gain in constitutional thinness (CT) population in response to 4-week fat overfeeding, associated with an increase in resting energy expenditure and an emphasised anorexigenic hormonal profile.
In CT people, their energy expenditure increases in line with their energy intake. Therefore, even though they're eating more Calories, there's no caloric surplus, therefore there's no weight gain. Energy Balance always applies.
- "Yes, kcals do get wasted. You don't understand things quantitatively i.e. how many kcals get wasted."
Just because it is *impossible* for a reasonable free living human to quantify all of the metabolic, endocrine, nervous system factors influencing adipocyte growth changes does not mean they don't fucking exist."
ItsTheWoo left out my calculations. Here they are:-"if I eat 2000 calories of a ketogenic diet in 3 hrs, most of it is wasted as heat, physical energy (I know, because I am EXTREMELY warm/energetic) and then the rest of time i am using a relatively greater percent of stored fat."
Do you know at what rate you're burning-off extra energy intake as heat energy output when you're "EXTREMELY warm/energetic"? Here's an estimate:-
If the mean TEF for your meal is 11% (assuming your meal is 50%E protein & 50%E fat), that's 220kcals (921kJ) "wasted" as heat energy. That'll make you feel EXTREMELY warm, as 220kcal raises the temperature of 57kg of water (your body) by 3.84°C.
A 2,000kcal meal (a whole day's worth of food) takes a lot longer than 3 hours to digest & absorb. I'll guesstimate it as 24 hours. 921kJ of extra heat power over the course of 24 hours = 10.7W, which is an increase of 17.7% over your normal Metabolic Rate of ~60W heat power (~1kcal/minute).
It's easy to "prove" something by being vague. That's PSEUDOSCIENCE. I do science. If you do the maths, you can see that, of the 2,000kcal ketogenic meal, most of it isn't wasted as heat, because if most of it is wasted as heat, ItsTheWoo would spontaneously combust!
- "Dr. Robert C. Atkins made the same fundamental cock-up when he said that humans pissed-out loads of kcals of ketones each day, giving a Metabolic Advantage to ketogenic diets."
2) If atkins was wrong (you pee out all LCHF food) who cares? That was 30+ years ago. He was a cardiologist who observed a VLC diet made him slim. He used his medical education to hypothesize a reason why. His hypothesis was wrong, but his observations were right. This happens all the time in science or basic human reasoning; make observations, form hypothesis. The hypothesis may be wrong, the findings are STILL RIGHT (i.e. low carb diets DO make slim, just not via peeing away ketones)."
1) There is no Metabolic Advantage to ketogenic diets. See http://www.jbc.org/content/92/3/679.full.pdf
2) Atkins' observations were wrong. See The Battle of the Diets: Is Anyone Winning (At Losing?)
a) Low-Carb diets work better than High-Carb diets for people who are Insulin Resistant.
b) Low-Carb diets work worse than High-Carb diets for people who are Insulin Sensitive.
c) Low-Carb diets work the same as High-Carb diets for everybody in Metabolic Ward Studies.
If there's a Metabolic Advantage to ketogenic diets, they would work better than high-carb diets all the time. They don't. See How low-carbohydrate diets result in more weight loss than high-carbohydrate diets for people with Insulin Resistance or Type 2 Diabetes for my hypothesis, which explains a), b) and c).
8 Ağustos 2014 Cuma
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.
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:-
Did you know that Human erythrocytes (red blood cells) are loaded with cholesterol and that 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.
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:-
Did you know that Human erythrocytes (red blood cells) are loaded with cholesterol and that 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.
7 Ağustos 2014 Perşembe
Chowdhury et al, More forests & more trees and more "Eureka!" moments with cheese.
Like Siri-Tarino et al, Forests & Trees and "Eureka!" moments, Chowdhury et al is a meta-analysis of many studies. See Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. I don't have access to the full study, but Google Image Search found Figure 2.
All saturated fatty acids have a RR for CHD of 1.06 (95% CI 0.86 - 1.30).
∴ There's no association between saturated fat intake and the RR for CHD.
Before VLC'ers do a dance of joy, consider the Forest plot for individual saturated fatty acids.
Palmitic acid has a RR for CHD of 1.15 (95% CI 0.96 - 1.37).
Stearic acid has a RR for CHD of 1.23 (95% CI 0.93 - 1.61).
Red meat & saturated fats synthesised by DNL aren't looking too good. However...
Pentadecanoic acid has a RR for CHD of 0.94 (95% CI 0.67 - 1.32).
Margaric acid has a RR for CHD of 0.77 (95% CI 0.63 - 0.93).
Pentadecanoic acid and Margaric acid combined have a RR for CHD of 0.81 (95% CI 0.62 - 1.06).
What are Pentadecanoic acid & Margaric acid found in? The clue's in the title:-
Say cheese: saturated fat in dairy may protect against diabetes.
The article in the Telegraph is actually referring to Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study.
Of the omega-3 fatty acids...
Eicosapentaenoic acid has a RR for CHD of 0.78 (95% CI 0.65 - 0.94).
Docosahexaenoic acid has a RR for CHD of 0.79 (95% CI 0.67 - 0.93).
Eicosapentaenoic acid and Docosahexaenoic acid combined have a RR for CHD of 0.75 (95% CI 0.62 - 0.89).
Of the omega-6 fatty acids...
Arachidonic acid has a RR for CHD of 0.83 (95% CI 0.74 - 0.92).
Of the trans-fatty acids...
Trans-oleic acid has a RR for CHD of 1.20 (95% CI 0.39 - 3.73).
Trans-linoleic acid has a RR for CHD of 1.36 (95% CI 0.83 - 2.22).
 |
| From http://annals.org/data/Journals/AIM/929862/6ff2_Figure_2_RRs_for_coronary_outcomes_in_prospective_cohort_studies_of_circulating_fatty_acid.jpeg |
All saturated fatty acids have a RR for CHD of 1.06 (95% CI 0.86 - 1.30).
∴ There's no association between saturated fat intake and the RR for CHD.
Before VLC'ers do a dance of joy, consider the Forest plot for individual saturated fatty acids.
Palmitic acid has a RR for CHD of 1.15 (95% CI 0.96 - 1.37).
Stearic acid has a RR for CHD of 1.23 (95% CI 0.93 - 1.61).
Red meat & saturated fats synthesised by DNL aren't looking too good. However...
Pentadecanoic acid has a RR for CHD of 0.94 (95% CI 0.67 - 1.32).
Margaric acid has a RR for CHD of 0.77 (95% CI 0.63 - 0.93).
Pentadecanoic acid and Margaric acid combined have a RR for CHD of 0.81 (95% CI 0.62 - 1.06).
What are Pentadecanoic acid & Margaric acid found in? The clue's in the title:-
Say cheese: saturated fat in dairy may protect against diabetes.
The article in the Telegraph is actually referring to Differences in the prospective association between individual plasma phospholipid saturated fatty acids and incident type 2 diabetes: the EPIC-InterAct case-cohort study.
Of the omega-3 fatty acids...
Eicosapentaenoic acid has a RR for CHD of 0.78 (95% CI 0.65 - 0.94).
Docosahexaenoic acid has a RR for CHD of 0.79 (95% CI 0.67 - 0.93).
Eicosapentaenoic acid and Docosahexaenoic acid combined have a RR for CHD of 0.75 (95% CI 0.62 - 0.89).
Of the omega-6 fatty acids...
Arachidonic acid has a RR for CHD of 0.83 (95% CI 0.74 - 0.92).
Of the trans-fatty acids...
Trans-oleic acid has a RR for CHD of 1.20 (95% CI 0.39 - 3.73).
Trans-linoleic acid has a RR for CHD of 1.36 (95% CI 0.83 - 2.22).
4 Ağustos 2014 Pazartesi
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
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.
 |
| 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.
3 Ağustos 2014 Pazar
Depression: The similarity between magnesium and ketamine in inducing amnesia for bad memories.
Here's a 2D-skeletal model of the ketamine molecule.
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.
-ketamine-from-xtal-2D-skeletal.png) |
| 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.
1 Ağustos 2014 Cuma
Negative feedback loops, Tolerance, Dependence & Withdrawal.
I couldn't find the plot that I was looking for, but this electrical plot is equivalent.
eA represents the amount of a substance that perturbs one of the body's negative feedback loops. The amount oscillates between 0V & 100V.
eR 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).
 |
| From http://www.tpub.com/neets/book9/37k.htm |
eA represents the amount of a substance that perturbs one of the body's negative feedback loops. The amount oscillates between 0V & 100V.
eR 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).
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