Alli on a high-fat diet

As I progress through this arduous task of shredding my body fat off, I've acquired a few new supplements to help and have done some testing. I'm on a limited budget so any new additions are at the expense of dropping less-effective others. Newest addition: Alli, also known as Xenical/Orlistat. And on a (relatively) high-fat diet, too. Probably not the expected "high-fat" (and high-carb) diet which GlaxoSmithKline ran their studies against; I do around 40% fat / 60% protein. These days I'm eating exclusively reduced-fat cheese. Why? Simply put, it works for me. Maybe it's the slow absorption of casein.

You've probably heard of the "treatment effects" of Alli, which even GSK admits. I wanted to put these treatment effect claims to the test, so on several occasions I started putting my $25 WAL-MART bought bottle of Alli to use. Orlistat is supposed to prevent up to 30% of fat calories from being absorbed. So it could be extremely useful when low-carb dieting for the purposes of fat loss since the greater the percentage of calories are of fat, the greater percent of calories is blocked.

First time use after meal of 2x10 servings full-fat sliced cheese and at least 5 tablespoons coconut oil - it took at least 12-16 hours to notice the notorious orange "effects". I did hear some sort of visceral growling noises before that time. Nothing uncontrollable, however, and certainly not as exaggerated as some authors make it. Maybe had to go to the restroom 5x or so to clear that meal. (that meal lasted me nearly 24 hrs). I took 6-8 pills while eating that meal.

After lower-calorie meals with less fat I've noticed no "treatment effect". For example, 8 slices of reduced-fat cheese.

After at least 800kcal worth of medium-chain triglycerides in my meal (with protein) and 8+ pills of Alli I noticed the worst treatment effects. Fortunately I was at home.
(On a side note, Giant started selling fat-free feta cheese ($3.99) recently and now I can create interesting combinations like feta cheese "fattened" with MCT oil!)

I think that the "treatment effects" of Alli can serve a functional purpose for me in helping me clear cheese out of my digestive system since it causes constipation. As for its intended use, it looks modestly effective in the sense that it slightly reduces (~10-15% for me) my net energy intake.

I've also dropped nicotine from my program since it doesn't seem to do anything useful now, and I don't see how it's even addictive. I've replaced it with ephedrine + caffeine + aspirin stack which DOES actually work for me.

Extended low-calories or fasting followed by 100% protein + medium-chain triglycerides (ONLY) re-feeding meal also seems to work.

artificial sweeteners and insulin

It's been said in the lower-carbohydrate forums that artificial sweeteners may raise insulin levels. Is this true? Read for yourself, but do so with a critical eye. To illustrate what I mean by that last statement, take this one study for instance, produced specifically to investigate the efficacy of a low-carb ketogenic diet vs. a low-carb-non-ketogenic diet. Note that Barry Sears is on the team of researchers. Then read this news article and hyperlipid's blog article if you have time.

Sucralose (aka Splenda)
You probably have heard enough about this artificial sweetener.

Here is the only study I've encountered on sucralose and insulin. Researchers concluded that

sucralose, delivered by intragastric infusion, does not stimulate insulin, GLP-1, or GIP release or slow gastric emptying in healthy humans

Unfortunately the full-text article is not free.

Stevia

Consensus appears to be that stevia is the most natural sweetener available. 300X as sweet as sucrose, still, to me it has a slightly bitter aftertaste when used independent of other sweeteners. Insulin response?

stevioside was able to regulate blood glucose levels by enhancing not only insulin secretion, but also insulin utilization in insulin-deficient rats

Erythritol

Erythritol is yet another sugar alcohol, similar to xylitol but reportedly less calories per gram. To me it tastes sweeter than, and maintains a sugar-like texture. From my experience it causes less gas and bloating. It comes across as more natural to me than sucralose and even if a bit pricier, it's currently my sweetener of choice.

Effect on insulin?

Less than 20% of erythritol remained unabsorbed and was available for colonic fermentation and potential production of short-chain fatty acids. Its caloric value was estimated to be < or = 0.4 kcal/g

Erythritol did not affect serum levels of glucose, insulin or other serum constituents

Free fatty acids and 3-hydroxybutyric acid [ketone] levels increased after erythritol administration

program fat cell death

I've come across some recent research which suggests how it may be possible to program fat cells toward self-destruction.
Anything that may inhibit lipogenesis or encourage lipolysis could be useful against the long-term war against obesity. Enough studies on medium-chain triglycerides have been conducted to where it's now a given that MCTs are stored less efficiently than LCTs. Not only this, but if this reduced fraction of MCTs even ends up as stored, it is able to mobilize out of fat tissue faster than LCTs. (reference)

Adiponectin

"Adiponectin exerts some of its weight reduction effects via the brain. This is similar to the action of leptin, but the two hormones perform complementary actions, and can have additive effects."

Leptin

In rats, brain administration of leptin causes deletion of adipocytes by apoptosis

MCFAs

One study concludes that MCFAs decrease adipocyte number by initiating adipocyte (fat cell) death.

Another study links C8 MCFAs to:
-a decrease in triglyceride synthesis
-reduction of lipogenic gene expression
-inactivation of PPARgamma

C8 MCFAs (octanoate) are again linked to PPARgamma expression.

"C8 may block adipogenesis at least in part by its influence on the expression/activation of PPARgamma."

Octanoate shows it can reduce TG synthesis and suppress de novo lipogenesis, both acutely and long term.

Another study involving isolated fat cells compared octanoate with oleate, a common LCT. Glycerol release was greater with octanoate, confirming this finding from other studies. Oleate induced fat cell differentiation whereas octanoate did not. Octanoate reached a maximum of 10% of fatty acids stored in fat cells.

neuropeptide Y (NPY) and leptin (new!)
"Rats fed with MCT diets had significantly higher ratios of hypothalamus/serum leptin in comparition with rats fed with LCT diets"

"Hypothalamus and serum NPY concentrations in rats fed with the MCT diets were more lower than those in rats fed with LCT diets"

Lower weight gain and higher expression and blood levels of adiponectin in rats fed medium-chain TAG compared with long-chain TAG

So the C8, C10 (octanoate, decanoate) medium-chain fatty acids appear to have the greatest effect on fat cells. I've found that MCT oil such as MCT Gold is entirely C8/C10 (67%/33%), and I'm using it liberally in my diet as a MCFA source.

C75

acts both centrally to reduce food intake and peripherally to increase fatty acid oxidation, leading to rapid and profound weight loss, loss of adipose mass, and resolution of fatty liver.

Dimethylaminopurine

At 100 micromol/L, DMAP completely inhibited the ability of insulin to counteract lipolysis in isolated adipocytes.

2,4-Dinitrophenol (DNP)

Once a prescribed fat-loss drug, is now banned by the FDA after thousands of people died from use. It has a low lethal dose. Not really sure if this has any relevance yet, but octanoate affects 2,4-dinitrophenol uncoupling.

Octanoate addition results in simultaneous increases in mitochondrial ATP/ADP ratio and oxygen uptake...Octanoate-related activation of oxygen uptake
might be explained by the direct supply of reducing equivalents
into the matrix, resulting in a rapid, although transient, increase
in the mitochondrial redox potential.

(More on uncoupling..."the increase in hepatic oxygen consumption due to addition of fatty acids reflects a mitochondrial process; it is, in part, independent of the ATP demand of the cell. An uncoupling-like effect of fatty acids on the respiratory chain and its possible physiological significance in ketogenesis are discussed.")

Docosahexaenoic acid (DHA, C22:6) aka "fish oil"

EPA or DHA, but primarily DHA may also induce lipolysis and as demonstrated in one study, fat cell death. Have a look:
"EPA/DHA may involve a metabolic switch in adipocytes that includes
"enhancement of beta-oxidation and upregulation of mitochondrial biogenesis" - potentially useful if planning to use mitochondria to burn fatty acids.
Docosahexaenoic acid inhibits adipocyte differentiation and induces apoptosis
Effects of seafood consumption and weight loss on ... [Eur J Nutr. 2009]
Adiponectin translation is increased by the PPARgamma agonists pioglitazone and omega-3 fatty acids
Individual fish-oil n-3 polyunsaturated fatty acid deposition and mobilization rates for adipose tissue of rats in a nutritional steady state -- Raclot and Groscolas 60 (1): 72 -- American Journal of Clinical Nutrition
Fish oil in a high lard diet prevents obesity, hyp... [Ann N Y Acad Sci. 1993]
Dietary fish oils limit adipose tissue hypertrophy... [Metabolism. 1990]

Nicotine

No research indicates fat cell death from nicotine, but nicotine appears to be a potent, not-necessarily-catecholamine mediated stimulator of lipolysis in both humans and rats. It increases basal lipolysis significantly, yet decreases that maximum lipolytic response to catecholamines. Meaning the preferred strategy of usage for me would be to use during times catecholamines are expected to be lower, such as far away from the cardio.

Systemic nicotine stimulates human adipose tissue lipolysis

Nicotine-infused rats gained 37% less weight and had 21% smaller fat pads. Basal lipolysis was 78% higher

Soy Isoflavones

Genistein Decreases Food Intake, Body Weight, and Fat Pad Weight and Causes Adipose Tissue Apoptosis

Soy has gotten a bad rap - deservedly so? - looked down upon or flat-out rejected for its inferior amino acid profile and acting as a phytoestrogen. I think there's probably a mainstream misconception that exaggerates the association between soy, femininity, and estrogen.
A good blog, Inhuman Experiment, has written on a study where soy reduced serum DHT and increased testosterone.

thyroid research - its fluctuation, and effects of exercise, circadian rhythm, meals , etc

It's recently been reported that my thyroid levels are below the normal threshold. So naturally I've taken an interest in investigating matters of "thyroid", and related.

Thyroid and Exercise Training

Most research appears to support the claim that thyroid is significantly influenced by exercise. Typically research indicates that the metabolic clearance rate of T4 increases with physical activity. This metabolic clearance is found in blood and in bodily tissues. The average increase in clearance rate is around 25%-35%. (In addition, the same studies discovered that catecholamine turnover is also higher from training. Thyroxine has demonstrated an increase in total adrenaline in the adrenal glands of rats.)

Exercise training caused changes in thyroid levels of male athletes, highly trained.

Another study shows that physical training stimulates the metabolism of thyroid hormones; increases thyroid use and turnover.

Conflicting studies on exercise
To be fair, study with mostly inconclusive results about thyroid levels in response to exercise,
T3, T4 levels were not affected by a bout of exercise, but growth hormone increased.

Thyroid respect to Diet
Plasma concentrations of T3 and T4 increased in response to high-fat, high-sugar, or high-calorie meals, possibly suggesting that a meal can induce the secretion of T4 or T3.
Thyroid hormone is associated with ketosis, where thyroid hormone availability is associated with lipolysis and ketogenesis.
Abstract goes on to inform us that norepinephrine increases ketogenesis by stimulating lipolysis. Nicotine stimulates the release of norepinephrine. Caffeine can also raise norepinephrine levels.

When % dietary fat was increased from 30% to 50% in this study, the formerly obese women showed a reduced T3/T4 ratio after a dinner meal.


Thyroid fluctuation with circadian rhythm:
Thyroid levels really can fluctuate in animals,
thyroid fluctuation evidence++,
in STARVED animals,
Thyroid axis and melatonin in humans,
Ketogenic Diet Disrupts the Circadian Clock

Composition of diet (low-fat/high-fat) altered the circadian rhythms in levels triiodothyronine (T3). In the high-fat diet. After 24 hrs of fasting, insulin and glucose were found to vary with time of day. However, in the high-fat diet oscillations in T3 were not detected, but for the low-fat diet they were.

More evidence of thyroid osciallations with respect to circadian rhythm. Interestingly, the oscillations were affected by fasting at 24 hr intervals, but not at 48 hr intervals. The point is that osciallations in thyroxine (T4), insulin, and glucose were affected by the time of day. The abstract mentions a "dependence of the stimulus on the time of day", and doesn't really explain much on what this stimulus is, but I assume they meant the stimulus of having a meal.

Regulation of UCP2
UCP2 is a mitochondrial protein, and studies continue to reveal its role in various tissues of the body.
In a study (yr 2000) on human subjects, UCP2 expression was markedly upregulated in the adipose tissue of subjects with higher thyroid activity.

physician visit II - lab results

Finally heard back on my lab results. Keep in mind that I go out of my way to consume exclusively saturated fats (mostly in the form of MCFAs).

	value	normal limits
T4	4.5	5.0-12.5 µq/dL
T3 uptake	33.9	22.5 - 37.0 %
TSH	1.655	0.350-4.500 µIU/mL
glucose	59	70-99 mg/dL
triglyceride	29	< 150 mg/dL
HDL	94	> 39 mg/dL
total chol/HDL ratio	1.7
VLDL	6	0-40 mg/dL
LDL	59	0-99 mg/dL
C02	16	19-32 mEq/L
albumin	5.3	3.5-5.2 g/dL

we're planning another test in the next couple weeks. If I have been experiencing symptoms of hypothyroidism, what's odd to me is that they only show up within particular periods of time; I think I see a correlation to my meal timing.

If hypothyroidism really is the issue (instead of only hypoglycemia), it probably relates to me repeatedly cutting weight, and now I may have made this problem surface by introducing new variables, such as: abruptly increasing the % fat in my diet, reducing activity level, suddenly switching to a high LCT fat + completely carnivorous diet and gaining fat, aggressively dropping weight while switching back to a high MCT diet, then increasing activity levels.

Fortunately I think I'm seeing some of the lethargy fade away, probably resulting from some loss of abdominal/visceral fat(?), keto-adaptation, possibly better energy utilization from increasing mitochondria from increasing exercise activity, and maybe the new OTC nicotine. The nicotine really has an antidepressant effect on me, uplifting even, although if taken in the evening can lead to nightmares for me.

According to Dr. Harris, keto-adaptation can take anywhere from 10 days to 6 weeks.



Studies on thyroid, sensitivity of thyroid levels, thyroid interactions, etc in next post.

ketones, mitochondria, brain

Here are studies related to ketones, their effect on the brain and mitochondrial proliferation within the brain. Recall that ketosis can be produced from calorie restriction, a low-carbohydrate ketogenic diet, or medium-chain triglycerides.

neuroprotective properties of potent tissue-specific effects of medium-chain fatty acids,

Induction of ketosis may improve mitochondrial function,


effects of a ketogenic diet on ATP concentrations and the number of hippocampal mitochondria
,

Mitochondrial biogenesis

Octanoate (C8), a medium-chain fatty acid, may contribute 20% of total brain energy production.
That's all for now. I'll be adding additional studies in the future.

"whey protein" or dairy; research

IGF-1

Apart from regulating somatic growth and metabolic processes, accumulating evidence suggests that the growth hormone (GH)/insulin-like growth factor-I (IGF-I) axis is involved in the regulation of brain growth, development, and myelination. In addition, both GH and IGF-I affect cognition and biochemistry in the adult brain. Some of the effects of GH are attributable to circulating IGF-I, while others may be due to IGF-I produced locally within the brain.

reference

Insulin-like growth factor I (IGF-I) is central to the somatotropic (growth hormone) axis. It promotes tissue growth and continues to have anabolic effects in adulthood. Accumulating evidence from the last decade, however, reveals that circulating levels of IGF-I also significantly affects cognitive brain function

reference

I found the hypothesis within this article to be a bit fascinating.

Milk evolved under continuous Darwinian selection pressure to nourish mammalian neonates. Evolutionary pressure appears to have led to the elaboration of a complex food...

milk products stimulate insulin secretion

milk protein, with respect to healthy AND type-2 diabetes persons, generates an insulin response.

Milk protein, in particular the whey fraction, has been shown to display insulinotrophic properties

whey causes IGF-1 response in boys over 7 days

another kids' study on IGF-1 and dairy products.

Kids' study III shows that 53g of milk protein was enough to double s-insulin and cause an increase in insulin resistance, while refuting the hypothesis that BCAAs per se stimulate insulin secretion and resistance

This study on men shows positive correlation of milk and IGF-1.

Intake of dairy food (especially low-fat milk) was also positively and moderately associated with plasma levels of IGF-I, IGFBP-3, and IGF-I/IGFBP-3 among control men.

cognitive

This shows whey can improve cognitive performance under conditions of stress.

Assuming whey protein elevates IGF-1 levels as shown in the preceding studies,
"serum IGF-I is an important mediator of neuronal growth, survival and function throughout the lifespan"

immunity, anticancer, antigenic properties

This PDF, though many mice studies are referenced, strongly supports that whey protein concentrate (WPC) exhibits anticarcinogenic and immunoprotective health benefits.

physician visit

Today I visited a physician to get a physical and blood work / lab test done. I've been doing intermittent fasting, and have recently been concerned that I may be experiencing hypoglycemia toward the end of the day. My thinking begins to get really foggy around 8-10 hrs into my intermittent fast, despite being on a highly ketogenic diet. If my memory serves me correctly, this began happening around the time I started increasing my total LCT intake past 60% total energy intake and swapping out MCTs entirely for LCTs...I think. Before then, my diet looked like 60%+ protein, the rest fat (mostly MCTs) and incidental carbs (i.e. in a serving of fat-free cheese or egg white).

The physician I visited did not support the diet I'm following and isn't familiar with say, Dr. Eades. She also remarked that coconut oil is bad for my arteries and triglyceride levels. Well, she has formal medical training, and I do not, so point taken. Fortunately, she ordered a complete lab test on my blood, so we should see what is truly going on within the next week.

Until then I will be increasing the meal frequency and activity level.

what are the long-term effects?

Much of the research done related to MCTs is performed over the short-term. What are the metabolic responses over the long-term; what happens after adapting to a MCT diet?

In this abstract, during a 44-day period rats were fed either low-fat (LF) and high-carb, 63% LCT, or 63% MCT diet. Energy retention and weight gain was less on the MCT diet, with a 60% reduction in adipogenesis.
Ketone body concentrations were most elevated in the MCT group, but by day 44, were reduced by 50%.

A study performed across 8 weeks on rats demonstrated that although little MCFA was incorporated into adipose tissue of the MCT group, fat deposition of MCFA can be accomplished by de novo fatty acids synthesis.

Personal experience tells me that the weight-loss effects of MCFAs are more pronounced in the short-term, but then attenuate over time.

insulin and ketosis

Studies have shown significant effects on insulin levels and ketosis following MCT ingestion. Insulin levels are of particular interest to low-carb or paleolithic dieters.

Insulin response

In this study, blood ketones were elevated after MCT ingestion, but despite a higher level of ketones which tends to exist with low levels of insulin, insulin was elevated as well. Additionally HGH increased for around 2 hours.

YYY and Zee acknowledge that

Medium-chain triglycerides (MCT) induce ketosis in several mammalian species including man.

Rats were fed either MCT or LCT. Ketone bodies increased 18x only 1 hr after MCT feeding vs 2x for corn oil (LCT). There's more in this lengthy yet concise list of results in the abstract and I suggest you have look. I find the authors' conclusion particularly informative

that ketosis induced by MCT stems from rapid oxidation of medium-chain fatty acids. Hyperinsulinemia, hypoglycemia and depressed lipogenesis resulting from MCT feeding appear to potentiate but not initiate ketosis.

Another study that examined parenteral nutrition for surgery patients demonstrated higher serum levels of insulin in the MCT group than the LCT group.

Chain length matters. The insulin output of capric (C10) and lauric acid is potent and to the magnitude of linoleate.

The insulin level was higher in patients undergoing digestive tract surgery.

MCFAs stimulated insulin secretion in young rabbits, where sunflower oil was ineffective.

Stimulation of insulin by free fatty acids per se was shown to be possible in a study on dogs.

Serum insulin levels in patients with cirrhosis were increased by pure MCTs between 30-120 min after MCT oil ingestion, but not in the fasted state.

No insulin response

Rat study, which compares the insulin response with MCTs vs LCTs

• diets were isocaloric
• dietary forms of MCFA or LCFA are not described

Where LCFAs affected the insulin response, MCFAs showed no effect.

17 healthy young men replaced 70g of their dietary fat with either MCTs or sunflower oil (LCTs). This was achieved by dietary intervention. The subjects were given 1500 calories of 45% fat, 47% carbohydrates,  7% protein. The rest of the subjects' daily intake is not known, except that they were instructed not to consume additional fat.

Fasting insulin was measured and was reported to not significantly differ between the two groups. Even still the fulltext mentions insulin stimulation from high MCT intake in its discussion. The focus of the study was actually on measuring lipid profile.

In 10 NIDDM (diabetes) subjects with 40% fat isocaloric diets, fasting serum insulin was measured to exhibit changes
...
Thus the insulinotropic effects of medium-chain triglycerides appear to be found postprandially.