EvoMuse Presents: KetoInduce V2

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Let's see who wants to take part in a life changing beta test while we wait for the final ingredient to arrive? Why should I pick you to test out this VERY expensive product to confirm my designs efficacy?

Dont hold back, son...let it all out.





Ketosis is a state of almost pure fat burning, drawing on fatty acid stores to form Ketones, which the body uses as fuel. Previously, incredibly disciplined diets were necessary to enter Ketosis, and the slightest carb intake would knock you right out. While the fat burning results are unmatched, the dedication required by non-competitive athletes makes it unfeasible for people with actual lives.



Recently I've been researching the tie in between Ketogenic metabolic states, whole body inflammation, NRF2 levels, Free Carnitine levels, succinate dehydrogenase levels, and PPAR alpha activation to take the product up several levels, making it the most potent (and original) Ketogenic Inducement product available on the market.



KetoInduce takes a special combination of ingredients, and with the a restriction of carbs away from an hour before bedtime, that helps to enter the body into a state of ketosis. While you won't be seeing that rapid fat loss 24 hours a day, you will get at least 8 hours (sleep time may vary) of high intensity results. You should remain in ketosis until the next's day's first carb intake.

Directions: restrict carb intake before bed time, preferably taking in no carbs at least an hour before. Mix one scoop of Orange-flavored KetoInduce with 8-12 ounces of water and drink - simple as that. Status can be monitored with over the counter purchased ketosticks.
 

dollar662

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In ...Would love to help test this. I also have a blood ketone monitor and could do blood monitoring before bed and in morning . I have 8 test strips left.

That and the fact I'm up at 2am posting I should get extra credit
 
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Piston Honda

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Let's say I have OG Ketoinduce, and a separate TTA supplement, and a PLCAR supplement. What dosage would you recommend? PM is fine; wouldn't expect you to possibly give away proprietary info. Confidentiality will be kept.
 
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Let's say I have OG Ketoinduce, and a separate TTA supplement, and a PLCAR supplement. What dosage would you recommend? PM is fine; wouldn't expect you to possibly give away proprietary info. Confidentiality will be kept.
It'll be going on the label anyway, a gram of each should be about right.
 
luckylefty811

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I'm in this would be perfect I'm running supernova and dcp again doing a keto diet and breaking the carb fast after 8pm everyday. I've lost 14 lbs in 8 weeks. I've started week 9 running low on my last dcp bottle this could help with the hunger I have in the mornings.

I'm going on vacation next week to Vegas for 3 days then it's back at it. I will still be doing my keto diet I just will have to find some good eating spots while I'm out there.
 

SilentSavage0523

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Im very interested in this. I took a short break from my keto diet and maintained my weight, but will getting back to it next week. I do have should we surgery next week so the first week after won't be to much but after that along with Dr prescribed rehab I will be back in the gym for conditioning, leg training, and one side upper body training. This would be a nice little addition to help move along and really nice to see how much it helps while I'm not at full strenght.
Also curious for the logs what else would you like to see with this one besides just monitoring with keto sticks and such. Anything special or different
 
koltink

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I'd be in on this, I have about 150 carbs a day but they're all around my workout and am fasted for 2+ hours by the time I go to bed. I'd also pay for my beta, I like to support good people and a good company as much as I can
 
cheftepesh1

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Version one worked great for me, so I'm looking forward to the testing as I want to drop some more weight and cut down more. The bad part is V1 can't be found anywhere.
 
nicksox15

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In for results on this, definitely interested in trying this out. Currently logging a fat burner so not throwing my hat in the ring but excited to follow along/purchase when available
 
Tank999

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I am in ketosis usualy 26 days out of every 30. If I had a way to drop right back into ketosis, I would happily carb up pre and post workout. I work out usually 5 days a week. I have about 20-25lbs left to go of fat loss after over 3 years of dieting.
I am a long time fan of your products (just placed another order today). I would happily use, track, and log this.
Thanks for your consideration
 
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I'm going to try and transfer from Facebook over to here the thinking behind the KI Upgrade.....

Ok, this will take a few steps so bear with me. Initially we have PPAR Alpha activation ---> fgf21 increases .

https://www.ncbi.nlm.nih.gov/m/pubmed/17601491/


↓ Full text
PPARalpha is a key regulator of hepatic FGF21.
Lundåsen T, et al. Biochem Biophys Res Commun. 2007.
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Abstract

The metabolic regulator fibroblast growth factor 21 (FGF21) has antidiabetic properties in animal models of diabetes and obesity. Using quantitative RT-PCR, we here show that the hepatic gene expression of FGF21 is regulated by the peroxisome proliferator-activated receptor alpha (PPARalpha). Fasting or treatment of mice with the PPARalpha agonist Wy-14,643 induced FGF21 mRNA by 10-fold and 8-fold, respectively. In contrast, FGF21 mRNA was low in PPARalpha deficient mice, and fasting or treatment with Wy-14,643 did not induce FGF21. Obese ob/ob mice, known to have increased PPARalpha levels, displayed 12-fold increased hepatic FGF21 mRNA levels. The potential importance of PPARalpha for FGF21 expression also in human liver was shown by Wy-14,643 induction of FGF21 mRNA in human primary hepatocytes, and PPARalpha response elements were identified in both the human and mouse FGF21 promoters. Further studies on the mechanisms of regulation of FGF21 by PPARalpha in humans will be of great interest.
PMID 17601491 [PubMed - indexed for MEDLINE]

So we have activation of PPAR alpha increasing levels of FGF21. Who cares?
 
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Well as it turns out

FGF21------> increase insulin sensitivity and dramatic lowering of body fat (anti-obesity)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5431415/

Metabolic role of fibroblast growth factor 21 in liver, adipose and nervous system tissues
Xiaolong Lin,1,* Yuan Bo Liu,2,* and Huijun Hu1
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Abstract

The hepatokine fibroblast growth factor 21 (FGF21) is a novel polypeptide ligand, which is involved in glucose and lipid metabolism, and contributes significantly to lowering body weight and enhancing insulin sensitivity. A large number of pre-clinical and clinical results demonstrate that FGF21 is a potential drug target for treating obesity and type 2 diabetes mellitus. In the present review, the tissue specific actions and molecular mechanisms of FGF21 are discussed with a focus on the liver, adipose tissue and nervous system, as well as investigating the outcomes of clinical trials of FGF21, with the aim of interpreting and delineating the complexity physiology of FGF21.

So why not take DCP and be done with it? Well, while DCP is highly recommended stacked with KetoInduce, there is a special timing and synergy involved.

For one, let's look at whole body inflammation:

FGf21-----> correlated with healthy, controlled whole body inflammatory states

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5302167/

Endocr Connect. 2017 Jan; 6(1): 39–43.
Published online 2017 Jan 9. doi: 10.1530/EC-16-0103
PMCID: PMC5302167
LPS infusion suppresses serum FGF21 levels in healthy adult volunteers
Esben S Lauritzen,corresponding author1,2 Nikolaj Rittig,1,2 Ermina Bach,1,2 Niels Møller,1,2 and Mette Bjerre1
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Abstract
Context

During the inflammatory acute phase response, plasma glucose and serum triglycerides are increased in humans. Fibroblast growth factor (FGF) 21 has plasma glucose and lipid-reducing actions, but its role in the acute inflammatory response in human is unknown.
Objective

To investigate circulating levels of FGF21 after lipopolysaccharide (LPS) infusion.
Design

Two randomized, single-blinded, placebo-controlled crossover trials were used.
Setting

The studies were performed at a university hospital clinical research center.
Patients and interventions

Study 1 (LPS bolus): Eight young, healthy, lean males were investigated two times: (1) after isotonic saline injection and (2) after LPS injection (bolus of 1 ng/kg). Each study day lasted 4 h. Study 2 (continuous LPS infusion): Eight, healthy males were investigated two times: (1) during continuously isotonic saline infusion and (2) during continuous LPS infusion (0.06 ng/kg/h). Each study day lasted 4 h. Circulating FGF21 levels were quantified every second hour by an immunoassay.
Results

A LPS bolus resulted in a late suppression (t = 240 min) of serum FGF21 (P = 0.035). Continuous LPS infusion revealed no significant effects on FGF21 levels (P = 0.82).
Conclusions

Our studies show that a bolus of LPS results in decreased FGF21 levels 4 h from exposure.
Keywords: FGF21, LPS, inflammation

As we've established, whole body inflammation is bad for leaning out, but most especially acute inflammation, which lowers FGF-21 levels. So what does that have to do with short term induced ketosis and how does this all relate? (by the way I highly recommend scanning the full texts of these studies)

CREB3L3 is essential for fatty acid oxidation. Both ketosis and PPAR alpha mediated beta oxidation are dependent on this protein, which starts to indicate that the processes of ketosis and PPAR mediated fat burning are closely related.

CREB3L3 controls fatty acid oxidation and ketogenesis in synergy with PPARα
Yoshimi Nakagawa,a,1,2 Aoi Satoh,1 Hitomi Tezuka,1 Song-iee Han,1 Kenta Takei,1 Hitoshi Iwasaki,1 Shigeru Yatoh,1 Naoya Yahagi,1 Hiroaki Suzuki,1 Yasumasa Iwasaki,3 Hirohito Sone,4 Takashi Matsuzaka,1 Nobuhiro Yamada,1 and Hitoshi Shimanob,1,2,5
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Abstract

CREB3L3 is involved in fatty acid oxidation and ketogenesis in a mutual manner with PPARα. To evaluate relative contribution, a combination of knockout and transgenic mice was investigated. On a ketogenic-diet (KD) that highlights capability of hepatic ketogenesis, Creb3l3−/− mice exhibited reduction of expression of genes for fatty oxidation and ketogenesis comparable to Ppara−/− mice. Most of the genes were further suppressed in double knockout mice indicating independent contribution of hepatic CREB3L3. During fasting, dependency of ketogenesis on CREB3L3 is lesser extents than Ppara−/− mice suggesting importance of adipose PPARα for supply of FFA and hyperlipidemia in Creb3l3−/− mice. In conclusion CREB3L3 plays a crucial role in hepatic adaptation to energy starvation via two pathways: direct related gene regulation and an auto-loop activation of PPARα. Furthermore, as KD-fed Creb3l3−/− mice exhibited severe fatty liver, activating inflammation, CREB3L3 could be a therapeutic target for NAFLD.

Are you sure about that?

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5187893/

Int J Mol Sci. 2016 Dec; 17(12): 2093.
Published online 2016 Dec 13. doi: 10.3390/ijms17122093
PMCID: PMC5187893
Regulation of Ketone Body Metabolism and the Role of PPARα
Maja Grabacka,1,* Malgorzata Pierzchalska,1 Matthew Dean,2 and Krzysztof Reiss2
Béatrice Desvergne, Academic Editor
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This article has been cited by other articles in PMC.
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Abstract

Ketogenesis and ketolysis are central metabolic processes activated during the response to fasting. Ketogenesis is regulated in multiple stages, and a nuclear receptor peroxisome proliferator activated receptor α (PPARα) is one of the key transcription factors taking part in this regulation. PPARα is an important element in the metabolic network, where it participates in signaling driven by the main nutrient sensors, such as AMP-activated protein kinase (AMPK), PPARγ coactivator 1α (PGC-1α), and mammalian (mechanistic) target of rapamycin (mTOR) and induces hormonal mediators, such as fibroblast growth factor 21 (FGF21). This work describes the regulation of ketogenesis and ketolysis in normal and malignant cells and briefly summarizes the positive effects of ketone bodies in various neuropathologic conditions.

Interesting...driven in part by nutrient sensors (we have another product (or two, eventually) that uses nutrient sensors to dramatically change phenotype, namely using the Leptin system)

How do haywire nutrient sensors and modern Western diet have us in this predicament to begin with? There is controversy here, but...

ChREBP and Fgf21 in adaptive fructolysis and metabolic normalization despite excess fructose intake.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220398/

Mol Metab. 2017 Jan; 6(1): 14–21.
Published online 2016 Nov 23. doi: 10.1016/j.molmet.2016.11.008
PMCID: PMC5220398
A critical role for ChREBP-mediated FGF21 secretion in hepatic fructose metabolism
ffolliott M. Fisher,1 MiSung Kim,1 Ludivine Doridot,1 Jeremy C. Cunniff,1 Thomas S. Parker,2 Daniel M. Levine,2 Marc K. Hellerstein,3 Lisa C. Hudgins,2 Eleftheria Maratos-Flier,1,∗ and Mark A. Herman1,∗∗,4
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Abstract
Objective

Increased fructose consumption is a contributor to the burgeoning epidemic of non-alcoholic fatty liver disease (NAFLD). Recent evidence indicates that the metabolic hormone FGF21 is regulated by fructose consumption in humans and rodents and may play a functional role in this nutritional context. Here, we sought to define the mechanism by which fructose ingestion regulates FGF21 and determine whether FGF21 contributes to an adaptive metabolic response to fructose consumption.
Methods

We tested the role of the transcription factor carbohydrate responsive-element binding protein (ChREBP) in fructose-mediated regulation of FGF21 using ChREBP knockout mice. Using FGF21 knockout mice, we investigated whether FGF21 has a metabolic function in the context of fructose consumption. Additionally, we tested whether a ChREBP-FGF21 interaction is likely conserved in human subjects.
Results

Hepatic expression of ChREBP-β and Fgf21 acutely increased 2-fold and 3-fold, respectively, following fructose gavage, and this was accompanied by increased circulating FGF21. The acute increase in circulating FGF21 following fructose gavage was absent in ChREBP knockout mice. Induction of ChREBP-β and its glycolytic, fructolytic, and lipogenic gene targets were attenuated in FGF21 knockout mice fed high-fructose diets, and this was accompanied by a 50% reduction in de novo lipogenesis a, 30% reduction VLDL secretion, and a 25% reduction in liver fat compared to fructose-fed controls. In human subjects, serum FGF21 correlates with de novo lipogenic rates measured by stable isotopic tracers (R = 0.55, P = 0.04) consistent with conservation of a ChREBP-FGF21 interaction. After 8 weeks of high-fructose diet, livers from FGF21 knockout mice demonstrate atrophy and fibrosis accompanied by molecular markers of inflammation and stellate cell activation; whereas, this did not occur in controls.
Conclusions

In summary, ChREBP and FGF21 constitute a signaling axis likely conserved in humans that mediates an essential adaptive response to fructose ingestion that may participate in the pathogenesis of NAFLD and liver fibrosis.

Yep, the old evil Fructose. No, it's not evil or the devil, but does have metabolic effects out of proportion to the little role that it SHOULD play in your nutritional lives.

Ok, so you've spit out some big words and pointed at some pathways. We're all super impressed. What does it all mean?With a drop in FGF21 during ketosis as well as during periods of acute inflammation, and the dependency on FGF21

FGF21 and formation and usage of ketone bodies, inflammation, and tissue specificity...

Ketogenic Diet Impairs FGF21 Signaling and Promotes Differential Inflammatory Responses in the Liver and White Adipose Tissue

Abstract
Background/Hypothesis

Beside its beneficial effects on weight loss, ketogenic diet (KD) causes dyslipidemia, a pro-inflammatory state involved in the development of hepatic steatosis, glucose intolerance and insulin resistance, although the latter is still being debated. Additionally, KD is known to increase fibroblast growth factor 21 (FGF21) plasma levels. However, FGF21 cannot initiate its beneficial actions on metabolism in these conditions. We therefore hypothesized and tested in the present study that KD may impair FGF21 signaling.
Methods/Results

Using indirect calorimetry, we found that KD-fed mice exhibited higher energy expenditure than regular chow (RC)-fed mice associated with increased Ucp1 levels in white adipose tissue (WAT), along with increased plasma FGF21 levels. We then assessed the effect of KD on FGF21 signaling in both the liver and WAT. We found that Fgfr4 and Klb (β-klotho) were downregulated in the liver, while Fgfr1 was downregulated in WAT of KD-fed mice. Because inflammation could be one of the mechanisms linking KD to impaired FGF21 signaling, we measured the expression levels of inflammatory markers and macrophage accumulation in WAT and liver and found an increased inflammation and macrophage accumulation in the liver, but surprisingly, a reduction of inflammation in WAT.We also showed that KD enhances lipid accumulation in the liver, which may explain hepatic inflammation and impaired Fgfr4 and Klb expression. In contrast, import of lipids from the circulation was significantly reduced in WAT of KD-fed mice, as suggested by a downregulation of Lpl and Cd36. This was further associated with reduced inflammation in WAT.
Conclusion

Altogether, these results indicate that KD could be beneficial for a given tissue but deleterious for another.


Important to note here is the increase of inflammation (and reduction of FGF-21 signaling in the liver, with reduced inflammation and unimpeded signaling in subcutaneous white adipose tissue as well as increased levels of UCP1 in sWAT. These are ideal conditions to increase the browning of sWAT, if only there were some magical product that's already designed to increase browning of subcutaneous WAT that we could combine with cyclic burst ketogenic states....

So what can we do to take advantage of these short burst cyclic ketogenic states, and how to we make sure that we are setting up the conditions for ideal change in body fat levels without wasting time, balancing these various factors in as little time as possible, then riding them out when it takes little to no effort at all - namely during sleep?

Bsically, what's the point you're trying to make?

WARNING: This is a long one

http://www.sciencedirect.com/…/article/pii/S1550413107001374

Hepatic Fibroblast Growth Factor 21 Is Regulated by PPARα and Is a Key Mediator of Hepatic Lipid Metabolism in Ketotic States
Cell Metabolism, Volume 5, Issue 6, 6 June 2007, Pages 426-437
PDF (1MB)

A sufficient energy supply is essential for life; consequently, multiple mechanisms have evolved to ensure both energy availability and conservation during fasting and starvation. Two reports in this issue of Cell Metabolism (Badman et al., 2007; Inagaki et al., 2007) demonstrate that FGF21, a circulating protein produced in the liver in response to the PPARα transcription factor, is a “missing link” in the biology of fasting, inducing adipose tissue lipolysis, liver ketogenesis, and metabolic adaptation to the fasting state.
Main Text
Biology of Fasting

The adaptation from the fed to fasted (total lack of food intake, usually acute) or starved (chronic undernutrition) state has been a subject of fascination, and investigation, for centuries (Cahill, 2006; Keys et al., 1950; see also Tucker, 2006). In the fed state, glucose fulfills the body's acute, immediate energy needs. The body senses a drop in glucose concentration at sites such as the pancreatic islets, brain, and portal vein. It responds by reducing insulin secretion from islet β cells and by increasing glucagon secretion from islet α cells. Another response is sympathetic adrenal stimulation causing increased epinephrine levels; this arm is of secondary importance but has a larger role in patients with type 2 diabetes (Cryer et al., 2003).

During fasting, liver glycogen, a glucose-storage polymer, is initially mobilized to replenish blood glucose (glycogenolysis). Major changes in metabolism occur as the glycogen supply dwindles. Stored adipose tissue triglycerides are released into the circulation as glycerol and fatty acids. The glycerol is converted by the liver into glucose (gluconeogenesis). The fatty acids are directly oxidized as an energy source by some tissues (liver and muscle); the liver also metabolizes the fatty acids to β-hydroxybutyrate and acetoacetate (“ketone bodies”). Ketone bodies are released into the circulation for use by tissues, notably the brain, which cannot use fatty acids. The liver also uses ketones for gluconeogenesis. When fasting is prolonged, muscle protein breakdown occurs, sending alanine to the liver as another substrate for gluconeogenesis (Cahill, 2006).

The major controllers of energy homeostasis are insulin, glucagon, and the sympathetic nervous system, but other regulator hormones play a role too. Leptin is secreted by adipose tissue in proportion to adipose triglyceride content (the determinant of how long the body can survive starvation); this information on triglyceride levels controls chronic energy homeostasis and related events, including, for example, the ability to reproduce. Other physiological signals of energy status include the gut hormones that communicate nutritional status (examples include ghrelin, cholecystokinin, pancreatic polypeptide, glucagon-like peptide-1, polypeptide YY, gastrin-releasing peptide, and neuromedin U). None of these gut hormones, however, has the dramatic, nonredundant importance of insulin, glucagon, or leptin, as evidenced by the deficiency phenotypes of the respective knockout mice. Hypothetical roles for as yet undiscovered hormones might include hormones secreted by the liver reporting its glycogen or triglyceride content, or by muscle broadcasting that its glycogen stores are low or that its lactate production is high.

Over the past few years, it has become clear that there is another source of “hormonal” information on fuel homeostasis. There are now a number of examples of the metabolic fuels themselves serving as hormones (i.e., as ligands without undergoing further metabolism). Metabolic substrate G protein-coupled receptors include GPR109A for β-hydroxybutyrate, GPR91 for succinate, GPR99 for α-ketoglutarate, and GPR41 and GPR43 for short-chain fatty acids. Intracellular transcription factors that appear to be fuel sensors are HNF4 and PPARs for fatty acids (among others; see Lazar and Willson, 2007).
FGF21

FGF21 burst into the picture when Kharitonenkov et al. (2005) showed that it improved glucose, insulin, and triglyceride levels in diabetic mice and that transgenic overexpression resulted in a lean, insulin-sensitive phenotype. A follow-up study of 6 weeks' treatment of diabetic rhesus monkeys significantly expanded these results: FGF21 reduced glucose, insulin, and glucagon levels; improved lipid profiles; and slightly reduced body weight (Kharitonenkov et al., 2007). Of significant interest for identifying possible pharmaceutical targets, no signals of hypoglycemia or cell proliferation were detected.

The two papers in this issue (Badman et al., 2007; Inagaki et al., 2007) establish FGF21 as a hormone important in the intermediate time period (hours) in the body's adaptation to fasting. The papers complement each other well, with Inagaki et al. concentrating on FGF21 excess, showing that it is sufficient, while Badman et al. focus on FGF21 deficiency (liver knockdown), showing that it is necessary, for adaptation to fasting (Figure 1).
Biology of FGF21 in Liver, Brain, and Adipose TissueFuels are shown in black…

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Figure 1. Biology of FGF21 in Liver, Brain, and Adipose Tissue

Fuels are shown in black italics, and regulators are shown in red. FGF21 actions on liver are depicted as endocrine but could also be paracrine. Fasting is detected by the brain, leading to lipolysis and contributing to other adaptations such as torpor. Fatty acids are released from adipose tissue, taken up by the liver, and either oxidized or converted to ketones. Ketones released by the liver are used as fuel by the brain. Activation of PPARα, presumably via activation by fatty acids, increases transcription of FGF21. FGF21 contributes to ketogenesis in liver, lipolysis in adipose, and adaptation such as torpor by the brain.

Both groups place FGF21 downstream of the transcription factor PPARα (the target of the fibrate class of triglyceride-lowering drugs), which has been identified as a key regulator of the adaptation to fasting (Lefebvre et al., 2006). They report that fasting or PPARα agonist treatment increased liver FGF21 mRNA levels about 25-fold. PPARα−/− mice showed reduced basal FGF21 mRNA levels with no response to PPARα agonist and only a partial increase in FGF21 mRNA upon fasting. Inagaki et al. (2007) demonstrate PPAR binding elements in the FGF21 promoter, suggesting that this is a direct effect, possibly mediated by fatty acid binding to PPARα. They show that in the fed state, FGF21 increases adipose tissue lipolysis and hepatic ketogenesis, increasing circulating β-hydroxybutyrate and reducing glucose, insulin, and cholesterol levels (confirming the findings of Kharitonenkov et al., 2005). The effects of FGF21 in the fed state mimic the adaptation to the fasted state seen in control mice. PPARα−/− mice are known to have an abnormal response to fasting, including defective fatty acid oxidation and ketogenesis (Kersten et al., 1999), defects that were partially remedied by FGF21 dosing. FGF21 also caused adipose lipolysis, providing fatty acids to the liver for ketogenesis, and induced torpor, a state characterized by physical inactivity and a low body temperature. Small mammals normally require a high metabolic rate in order to maintain body temperature but use torpor as an adaptive strategy to conserve energy when food is scarce.

Badman et al. (2007) identify FGF21 as a liver mRNA induced in mice subjected to fasting, fed a ketogenic diet, or treated with a PPARα agonist. Circulating FGF21 protein levels increased (about 2-fold) with fasting and returned to fed levels by 4 hr of refeeding but were only modestly reduced in the PPARα−/− mice. Interestingly, the elevated FGF21 mRNA levels of the ketogenic diet were not reduced in the PPARα−/− mice, indicating that induction of FGF21 can also be independent of PPARα. Adenovirus knockdown of liver FGF21 expression in mice on a ketogenic diet caused fatty liver, lipemia, and reduced serum ketones, with reductions in liver RNAs for fatty acid oxidation and ketogenesis genes. The combined observations that FGF21 regulates adipose (lipolysis), liver (fatty acid oxidation and ketogenesis), and brain (torpor) establish it as a major endocrine regulator of the response to fasting.
What Are the Unanswered Questions?

As with any new hormone, there is much to learn about FGF21's biology. For example: What role does it have in other ketogenic states, such as the newborn period, lactation, and pregnancy? Are some effects of FGF21 autocrine or paracrine, rather than endocrine? Does FGF21 reach the brain directly, or are its actions there indirect? A fascinating observation is that some seizure disorders that are unresponsive to other therapies are effectively treated by a ketogenic diet (Freeman et al., 2007). There is no clear mechanistic understanding for this success. Presumably FGF21 is induced in these patients. Might it also have a role in their treatment?

FGF21 is but one member of a 22-member family. However, three members, FGF21, FGF19 (Fgf15 in the mouse), and FGF23, constitute a distinct subfamily and share a number of attributes atypical for FGFs. The three appear to be classical endocrine hormones, being made in distinct sites (FGF21 in liver, FGF19/Fgf15 in intestine, and FGF23 in osteoblast) and acting distantly (FGF19/Fgf15 represses bile acid synthesis and inhibits gall-bladder emptying; FGF23 regulates phosphaturia and vitamin D metabolism). These FGFs bind heparin relatively poorly, presumably facilitating their endocrine rather than paracrine actions and their need for Klotho/β-Klotho receptor accessory proteins (Goetz et al., 2007).

What receptor (or receptors) is FGF21 acting through? There are four FGF receptor genes with tyrosine kinase activity, with multiple splice isoforms that affect specificity and thus receptor function. Additionally, receptor activity can be dependent on receptor-associated proteins. A recent paper shows that β-Klotho, a transmembrane protein that associates with FGF receptors 1c and 4, is required for FGF21 signaling in 3T3-L1 adipocytes (Ogawa et al., 2007). This is an exciting development that should help answer selectivity and specificity questions.

Is FGF21 a good drug candidate for diabetes, dyslipidemia, and/or obesity? The favorable diabetes and lipid phenotypes are encouraging. The rhesus studies (Kharitonenkov et al., 2007) suggest that these effects are not rodent specific (for example, due to the higher rodent liver PPARα levels or the importance of active brown adipose tissue). On the safety front, the lack of detected hypoglycemia or cell proliferation is important. Thus, this mechanism seems worthy of further investigation.

The observations reported in this issue by Badman et al. (2007) and Inagaki et al. (2007) identify FGF21 as an important endocrine hormone helping control adaptation to the fasted state. This provides a previously missing link, downstream of PPARα, by which the liver communicates with the rest of the body in regulating the biology of energy homeostasis.


So, while FGF21 is essentially required for ideal fat loss during states of perceived energy restriction like Ketosis, and PPAR alpha activation is not necessarily required to reach Ketosis, we are again looking to optimize our entry into ketosis and maximize time spent burning fatty acids. How can we do that, and make sure FGF21 levels are ideal?


https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5100287/
 
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Well, by making sure that both induction strategies are used - ketone/ketogenic state and PPAR-alpha activation, rapidly (rather than waiting for the tedious process of the body recognizing that it's in a lowered energy state during carb restriction, entering Ketosis, waiting for the liver to sense this and increase expression of PPAR Alpha, which in turn ensures high levels of the required FGF21 to get the most benefit from the ketogenic state, KetoInduce v2 provides these interdependent signals all at once so that maximal effects are experienced for a long amount of time during the sleep cycle.
 
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I'm still working on the Propionyl-L-Carnitine section, which will be here.
 
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Epilepsia. 2001 Nov;42(11):1445-51.
Carnitine levels and the ketogenic diet.
Berry-Kravis E1, Booth G, Sanchez AC, Woodbury-Kolb J.
Author information
Abstract
PURPOSE:

To determine the long-term effect of the ketogenic diet (KD) on carnitine levels and whether carnitine depletion is a significant cause of clinical complications during KD initiation or treatment.
METHODS:

Carnitine levels at 0, 1, 6, 12, and 24 months of diet treatment, carnitine antiepileptic drug (AED) history, lowest blood glucose and time to achieve ketosis during diet initiation, and diet complications were analyzed for 38 consecutive patients who initiated the KD from May 1997 to March 2000. Carnitine levels at follow-up were analyzed for eight patients started on the diet before to May 1997.
RESULTS:

Total carnitine (TC) at diet initiation correlated negatively with the number of AEDs at diet initiation but not with number of past AEDs, lowest blood glucose, or time to ketosis. TC decreased in the first months of diet treatment and then stabilized or increased slightly with long term treatment. Only 19% of patients were supplemented with carnitine for low TC. No patient showed clinical signs of carnitine deficiency.
CONCLUSIONS:

Multiple AED exposure lowers TC, but actual TC deficiency in patients initiating the KD is not common, and TC levels do not appear to predict hypoglycemia or problems achieving ketosis. Mild carnitine depletion may occur early in KD treatment and occasionally TC decreases out of the normal range, without clinical symptoms. TC stabilizes or increases back toward baseline with long-term treatment, and most patients do not require carnitine supplementation.

PMID:
11879348
 
dsade

dsade

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The role of forskolin here is interesting, and was a consideration (and perhaps still is) for inclusion in its enhancement of the CPT1 transport system. There is some indication of initial stages of ketosis causing a slight carnitine deficiency, for which we are including a low-medium dose of Propionyl-L-Carnitine, a form active in the heart, muscle, and liver.
 
cubsfan815

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How will flavoring be? Not to sound like a p***y, but when I take Ketoinduce and MCT I dry heave every time lmao
 
dsade

dsade

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How will flavoring be? Not to sound like a p***y, but when I take Ketoinduce and MCT I dry heave every time lmao
I'm going to be testing out a lemon like flavor.
 
DieselNY

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Very smart. Keep it citrus to mask the bhb taste
 
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