54 replies to this topic

[maxwatt]

I realized I would never get around to writing this if I properly documented every assertion, but they should be readily searchable in pubmed. If there is anything that is questionable, I'll try to back-fill.

We know resveratrol acts to increase SIRT1's effects. In addition it affects PPAR alpha and PPAR gamma. These increase mitochondrial biogenesis, an effect we have seen documented in rodents in Auwerx' papers, and effects in humans were reported in this forum by users. PPAR-gamma though stimulating mitochondria is also lipogenic, which is perhaps why we did not see any reports of dramatic weight loss reported here.

AICAR is a synthetic substance that agonizes PPAR-delta, which affects mitochondria without lipogenesis, but also requires SIRT1 to work. Besides mitochondrial biogenesis, effects reported in rodents were a 44% improvement in running time without exercise training. With exercise training the exercise time was double that. Other effects: weight loss, increase in muscle mass as seen in obese and normal human subjects. AICAR was reported to increase the amount of brown fat in adults (fat-burning fat). It was quickly banned in athletics, though it has turned up in pro cyclists' lockers. Testing is very expensive if it is possible at all. Although AICAR is putatively available over the internet, the identity of the substance is unverifiable to the average person, and it is prohibitively expensive in any case. To complicate things, there are two substances called AICAR, with different CAS numbers.

One advantage of AICAR over resveratrol is the dose; we have found heuristically in this forum that a minimally effective dose of resveratrol for improved athletic performance is around 400 mg, give or take. The effective dose for AICAR is an order of magnitude less, as little as 10 mg suggested in some body-building forums (those guys will swallow anything, even shit, if you said it increased muscle mass.) The human trials seemed to indicate a 40 mg dose in obese subjects, and dramatic weight loss was reported with an improvement in muscle mass, insulin resistance and blood sugar levels. Since AICAR and other PPAR-delta agonists need SIRT1 to work, adding a little resveratrol to the mix (less than needed for resveratrol's endurance effects) should be synergistic - assuming lower doses activate SIRT1, as some claim.

But AICAR is not readily available. However, a common prescription heart medication is available, and much cheaper. Micardis (Telemisartan) has recently been reported to be an effective PPAR-delta agonist. It has been on the market for years, still under patent in most countries. It is an

angiotensin II receptor antagonist used primarily to treat hypertension. It is sometimes used to treat metabolic syndrome, (elevated blood sugar

and insulin resistance.) But Micardis also is an effective PPAR-delta agonist.

I do not recommend running out to buy Micardis - a prescription is required. But if you have mild essential hypertension, you might try to get a prescription for it over other blood pressure meds. Adding a little resveratol should help even more with blood sugar and insulin resistance. For healthy people, I would expect the effects to include weight loss and improved exercise tolerance - exercise in a pill. Down-side, if you do attempt to obtain and use it without a prescription - something I am not recommending - it does lower blood pressure, and blood sugar. You would want to be monitored by a doctor, or at the very least use a blood pressure meter so you don't overdo it.

It is thought by some that chronic essential hypertension leads eventually to congestive heart failure by the time you are in your eighties, so it is well worth treating if your blood pressure is mildly elevated (over 130.) Perhaps a majority of people over 60 experience elevated systolic blood pressure, so this or other as yet unknown PPAR-delta agonists are worth pursuing. I'd certainly add some resveratrol to the mix to see if the expected synergy is there.

Edited by maxwatt, 06 March 2013 - 01:08 PM.

[tunt01]

In the area of supplements/longevity, this is where i have spent 80% of my thought the last few months (when I have time to look at this stuff).

I agree wholeheartedly w/ this post.

I've been thinking about taking AICAR for several months now, but held have held off for various reasons. I also wrote down Telmisartan in my notes as an alternative to AICAR. I've spent a lot of time looking at renoprotective substances and those 2 seem best.

One the concerns I have is how much AMPK is appropriate. How do we protect against this (given potential synergies w/ other substances) on a dosage and circadian rhythm basis? Because too much of anything is probably a bad idea.

Edited by prophets, 04 March 2013 - 08:17 AM.

[maxwatt]

In the absence of any guidelines from clinical trials or other data, titration of dosage and monitoring is the only thing available. FWIW, glucose is also essential for most tumor development, and reducing systemic levels (as PPAR-delta agonists do) would be expected to counter AMPK stimulation, at least to some extent. Further, resveratrol is an inhibitor of most tumor growth via apoptosis.

Looking through the paper Prophet's second link above refers to (Sang-Min Jeon and Nissim Hay), I see all the evidence is based on in vitro results with animal cell lines, and is a summary of other papers. I suspect the concentrations of AMPK used were beyond anything that can be obtained in vivo, but it would taking running down a half-dozen papers to be sure of this. In general, a higher NAD to NADH ratio is associated with longevity (in cell lines, perhaps in vivo as well.) I'd want to see this addressed as well as AMPK levels and absolute NADPH level. FWIW, a number of things increase NAD/NADPH ratio, including resveratrol and methylene blue.

Probably athletes are the best test group for this; AICAR and other PPAR-delta agonists have been used in endurance sports since 2006. They have been found in professional cyclist's lockers. We have not seen a cluster of tumor development in this group. Perhaps not the most robust epidemiological evidence, but still somewhat reassuring.

Edited by maxwatt, 04 March 2013 - 02:19 PM.

[maxwatt]

http://www.plosone.o...al.pone.0033815

An Ethanol Extract of Artemisia iwayomogi Activates PPARδ Leading to Activation of Fatty Acid Oxidation in Skeletal Muscle

[hav]

...
Although AICAR is putatively available over the internet, the identity of the substance is unverifiable to the average person, and it is prohibitively expensive in any case. To complicate things, there are two substances called AICAR, with different CAS numbers.
...

I've seen alcar on a variety of body building sites but got mine from purebulk. Don't see any coa there but they seem to be well regarded and offer it in two forms: pure and in combo with ala. I use the bulk form without the ala.

Didn't know it might go well with resveratrol. I take it because of studies that show it is neuroprotective and amplifies the ngf properties of lion's mane and codonopsis. It certainly amplifies their vivid dream effects in my experience. Once I added it into my mix I had to reduce from 400 mg each of lion's mane and codonopsis down to 45 mg each of the three of them to quell the amplified vivid dreams which wasn't the effect I was after. Been taking that combo for a couple of years now and still have all my hair.

Howard

[tunt01]

I've seen alcar on a variety of body building sites but got mine from purebulk.

he means aicar with an i.

Edited by prophets, 05 March 2013 - 05:47 AM.

[hav]

I've seen alcar on a variety of body building sites but got mine from purebulk.

he means aicar with an i.

Ah, ha! Thanks, prophets. Aicar (5-aminoimidazole-4-carboxamide-3-ribonucleoside) as opposed to Alcar (acetyl-L-carnitine). "Oh, that's very different....Never mind."

Emily Litella.

[tunt01]

stuff

happens in almost every thread discussing aicar. no worries.

[malbecman]

Here's a section on AICAR from the Wikipedia entry on Acadesine


5-Aminoimidazole-4-carboxamide riboside acts as an AMP-activated protein kinase agonist.^[5] It stimulates glucose uptake and increases the activity of p38 mitogen-activated protein kinases α and β in skeletal muscle tissue,^[6] as well as suppressing apoptosis by reducing production of reactive oxygen compounds inside the cell.^[7]
In 2008, researchers at the Salk Institute discovered that AICAR injected in experimental mice significantly improves their performance in endurance-type exercise, apparently by converting fast-twitch muscle fibers to the more energy-efficient, fat-burning, slow-twitch type. They also looked at the administration of GW 501516 (also called GW1516) in combination with AICAR. Given to mice that did not exercise, this combination activated 40% of the genes that were turned on when mice were given GW1516 and made to exercise. This suggests it may be possible to obtain some of the benefits of exercising without actually exercising.^[8] Because of the enhanced endurance effects, this could potentially be used by athletes to enhance their performance. One of the lead researchers from this study has developed a urine test to detect it and has made the test available to the International Olympic Committee, and the World Anti-Doping Agency has added AICAR to the prohibited list from 2009 onwards.^[9]

[edit]

[maxwatt]

I've seen alcar on a variety of body building sites but got mine from purebulk.

he means aicar with an i.

Ah, ha! Thanks, prophets. Aicar (5-aminoimidazole-4-carboxamide-3-ribonucleoside) as opposed to Alcar (acetyl-L-carnitine). "Oh, that's very different....Never mind."

Emily Litella.

Just to clarify things, we should refer to it as Aicar. or maybe AiCAR.

But two substances are called AICAR (=Aicar):

5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, called also Acadesine
5-Aminoimidazole-4-carboxamide ribonucleotide which is the Aicar we are are discussing here

Apparently much of the AiCAR sold to body builders on the internet is the wrong AiCar.

[tunt01]

Apparently much of the AiCAR sold to body builders on the internet is the wrong AiCar.

This explains it now. I was actually looking at ordering some a while back and I couldn't understand the wild variance in pricing among different source suppliers. Some were very cheap. I didn't spend much time thinking about it, but only found it odd/disconcerting.

[hav]

Just to clarify things, we should refer to it as Aicar. or maybe AiCAR.

But two substances are called AICAR (=Aicar):

5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, called also Acadesine
5-Aminoimidazole-4-carboxamide ribonucleotide which is the Aicar we are are discussing here

Apparently much of the AiCAR sold to body builders on the internet is the wrong AiCar.

Seems to be a mess. Did a little Pubmed searching and there seems to be a little more variation in chemical names referred to as AiCAR, with various positive effects, the cancer treatment ones overlapping:

AICAR, 5-aminoimidazole-4-carboxamide-1-β-d-riboruranoside: diabetes and exercise [probably a typo?]

5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AiCAR): blood pressure in insulin resistant rats

5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AiCAR): acute, exercise-induced activation of metabolic genes in skeletal muscle; increased the mRNA content of PGC-1alpha, HKII, FOXO1, PDK4, and UCP3

5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AiCAR): treatment of childhood acute lymphoblastic leukemia (ALL)

5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (adenesine): induces mitochondrial biogenesis but does not upregulate SIRT3 in mamal muscle

5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AiCAR): failed to block loss of muscle mass or induction of ubiquitin ligases upon denervation atrophy, although it prevented loss of mitochondria

There seem to be many studies about adenesine and exercise but the last one above about it failing to block loss of muscle mass probably wouldn't be encouraging to a body builder. The anti-cancer effect seems to overlap both forms.

5-aminoimidazole-4-carboxamideribonucleotide: treatment of refractory chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia

5-aminoimidazole-4-carboxamide ribonucleotide: anti-inflammatory effects

5-aminoimidazole-4-carboxamide ribonucleotide: treatment of enhanced susceptibility to exercise- and/or heat-induced sudden death associated with RYR1 mutations.

The only possible negative I came across suggested a general toxicity of the ribonucleotide form to nerve and brain cells (abstract) but a clear toxicity to neuroblastoma cells which sounds like a good thing.

Then there's this confusing study about AiCAR suppressing the growth of retinoblastoma in vivo where the abstract and full text refers to AiCAR as both the ribonucleotide and ribofuranoside forms in multiple places.

Unfortunately, the study about Aicar being an exercise mimic doesn't mention which Aicar they tested with:
AMPK and PPARδ agonists are exercise mimetics

Fwiw, the following study doesn't either, but one of the authors is the same and cites the above study as well as a study about 5-aminoimidazole-4-carboxamide ribonucleotide:
Exercise and PGC1α-independent Synchronization of Type I Muscle Metabolism and Vasculature by ERRγ

Howard

Edited by hav, 07 March 2013 - 01:51 AM.

[niner]

But two substances are called AICAR (=Aicar):

5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, called also Acadesine
5-Aminoimidazole-4-carboxamide ribonucleotide which is the Aicar we are are discussing here

Apparently much of the AiCAR sold to body builders on the internet is the wrong AiCar.

I think these are just different names for the same molecule. Ribose is a furanose.

[maxwatt]

5-Aminoimidazole-4-carboxamide ribonucleotide CAS number 3031-94-5 C₉H₁₅N₄O₈P

5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, CAS number 2627-69-2 C₉H₁₄N₄O₅

Both CAS number sometimes called Acadesine as well as AiCar. Wikipedia is often wrong, and Sigma Aldrich though more accurate, has made mistakes before. They say:
5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl 5′-monophosphate is 3031-94-5, and 2627-69-2 is 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside, Acadesine.

So I think Wikipedia entries need editing.

[hav]

5-Aminoimidazole-4-carboxamide ribonucleotide CAS number 3031-94-5 C₉H₁₅N₄O₈P

5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, CAS number 2627-69-2 C₉H₁₄N₄O₅

Both CAS number sometimes called Acadesine as well as AiCar. Wikipedia is often wrong, and Sigma Aldrich though more accurate, has made mistakes before. They say:
5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranosyl 5′-monophosphate is 3031-94-5, and 2627-69-2 is 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside, Acadesine.

So I think Wikipedia entries need editing.

That's consistent with what I found in ChemSpider:

5-Aminoimidazole-4-carboxamide ribonucleotide
ChemSpider name: AICA ribonucleotide
ChemSpider ID: 58620
Molecular Formula: C₉H₁₅N₄O₈P
Average mass: 338.211212 Da
Monoisotopic mass: 338.062744 Da
http://www.chemspide...ture.58620.html

5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside
Chemspider name: Acadesine
ChemSpider ID: 16560
Molecular Formula: C₉H₁₄N₄O₅
Average mass: 258.231293 Da
Monoisotopic mass: 258.096405 Da
http://www.chemspide...ture.16560.html

Howard

[tunt01]

Nothing new here really. Just an FYI. Turn on subtitles to translate from French.

[tunt01]

assuming one were to order AICAR from a somewhat sketchy website, anyone have any thoughts on where to get some AICAR tested to make sure it is of the quality/integrity as represented?

[tunt01]

Interesting article on AICAR and Micardis.

http://www.velonatio...-vigilance.aspx

Herman Ram adds. “We do think AICAR is a bit of a hype. It’s far too expensive and there are other things on the market that do the same, and better. And again it’s dangerous because it’s never been tested on humans.” But the latter point doesn’t deter the black market in doping, with a history of untested products being used.

Telmisartan is a prescription drug for high blood pressure. It’s accepted by the U.S. Food and Drug Administration and not on the WADA list, nor is the class of drugs to which it belongs. Only specifically named substances and substances that are not approved by government regulatory bodies are on that list.
...
Telmisartan is neither and, according to recent research by Fabian Sanchis Gomar of the University of Valencia, Spain, it has virtually the same specifics as AICAR and GW1516. It also enhances running ability in mice if they are completely untrained. With training, endurance increases, fat is burnt and recovery is faster as there is less lactic acid formation.
...
Herman Ram added that there is a thin line between what is admissible and what not. “In the end everything has an effect on something. So far there hasn’t been a reason to take a closer look on Telmisartan in this respect.”

Meanwhile, the substance has been found near cycling. During the same Tour de France raid in 2009 the AFLD-researchers found packages of Telmisartan. This was before research claimed similar characteristics as AICAR, and AFLD therefore couldn’t really explain its presence in a cycling-related environment.

Every chemist has access to Telmisartan and because it’s not experimental anymore, it is therefore widely available. If AICAR is on WADA’s forbidden list and Telmisartan - which might have the same effects - isn’t, the latter might be a way to escape detection.

[maxwatt]

Don't see why Telmisartan should be banned from sport. One would still have to be gifted and train like a son-o-a-bitch to be competitive and it doesn't appear dangerous under proper supervision.

Edited by maxwatt, 01 June 2013 - 12:16 PM.

[maxwatt]

This paper shows that an extract of bitter melon activates ppar-delta, this is consistent with its traditional uses to treat diabetes, hypertension, and dyslipidemia. PPAR agonists have these effects. A caveat, the extracts sold as supplements are quite varied, ranging from freeze-dried powder, 12:1 extracts, water or ethanolic extracts. I do not know from this abstract how the extract used was made, but it has been claimed that ethanolic extracts are more effective. Also the part of the plant used varies. Some use the leaves (which is rich in some but not all of the compounds also found in the fruit.) There are reports of children falling into hypoglycemic coma after eating traditional dishes using the fruit. It also appears not to be carcinogenic, as some of the synthetic PPAR-delta substances have proven to be.

It seems likely consumption of this herb or its extract would improve athletic performance. Would the sports governing bodies be justified in banning a vegetable that is commonly consumed and widely available?

J Atheroscler Thromb. 2009;16(6):888-92. Epub 2009 Dec 22.
Activating effect of momordin, extract of bitter melon (Momordica Charantia L.), on the promoter of human PPARdelta.

Sasa M, Inoue I, Shinoda Y, Takahashi S, Seo M, Komoda T, Awata T, Katayama S.

Source

Department of Diabetes and Endocrinology, Saitama Medical University, Japan.

Abstract


AIM:

Bitter melon (Momordica charantia L.) is a common vegetable grown in Okinawa that has also been used recently in medicine for the treatment of diseases such as diabetes, hypertension, and dyslipidemia. Among Bitter melon extracts compounds, we focused on an extract known as momordin in the present study, to examine its effect on peroxisome-proliferator activated-receptor (PPAR) delta (also called PPARdelta in rodents) expression and promoter activity of the human PPARdelta gene.
METHODS:

A human PPARdelta promoter-reporter plasmid was made as a template from a BAC CLONE (RPCI-11C) containing a -3076 bp (BglI site) +74 bp (EcoRI site) sequence. Luciferase assay of PPARdelta promoter activity was performed using HepG2 cells.
RESULTS:

10 and 25 nM Momordin significantly increased the expression of PPARdelta mRNA 1.5-fold (relative to the control). Moreover, 10 and 25 nM Momordin significantly increased PPARdelta promoter activity in a dose-dependent manner, reaching more than 1.5-fold relative to the control.
CONCLUSION:

Our present data obtained through successful cloning of the PPARdelta promoter demonstrate that PPARdelta production and activation are upregulated through PPARdelta promoter activity following momordin treatment. PMID: 20032574

Edited by maxwatt, 01 June 2013 - 12:31 PM.

[hav]

This paper shows that an extract of bitter melon activates ppar-delta, this is consistent with its traditional uses to treat diabetes, hypertension, and dyslipidemia. PPAR agonists have these effects. A caveat, the extracts sold as supplements are quite varied, ranging from freeze-dried powder, 12:1 extracts, water or ethanolic extracts. I do not know from this abstract how the extract used was made, but it has been claimed that ethanolic extracts are more effective.

...

I was able to locate the full-text here:

https://www.jstage.j.../6/16_2790/_pdf

It only mentions the chemical company they bought the Momordin from. When I looked up its properties, there was mention of using methanol to extract it. There was also mention that momordin was a metabolite of oleanolic acid. I also noticed in the paper that they dissolved the momordin in dmso to treat the cells which they tested in vitro.

Howard

[tunt01]

Arctigenin activates AMPK

http://www.ncbi.nlm....pubmed/22095235

[blood]

Honokiol (extracted from Magnolia) acts as a PPAR-gamma agonist, but unlike e.g. Pioglitazone doesn't seem to promote weight gain (in mice, at least).

Newish study:

http://www.ncbi.nlm....pubmed/23811337

Biochim Biophys Acta. 2013 Oct;1830(10):4813-9. doi: 10.1016/j.bbagen.2013.06.021. Epub 2013 Jun 27.

Honokiol: a non-adipogenic PPARγ agonist from nature.

Atanasov AG, Wang JN, Gu SP, Bu J, Kramer MP, Baumgartner L, Fakhrudin N, Ladurner A, Malainer C, Vuorinen A, Noha SM, Schwaiger S, Rollinger JM, Schuster D, Stuppner H, Dirsch VM, Heiss EH.

Source
Department of Pharmacognosy, University of Vienna, Vienna, Austria.

Abstract

BACKGROUND:
Peroxisome proliferator-activated receptor gamma (PPARγ) agonists are clinically used to counteract hyperglycemia. However, so far experienced unwanted side effects, such as weight gain, promote the search for new PPARγ activators.

METHODS:
We used a combination of in silico, in vitro, cell-based and in vivo models to identify and validate natural products as promising leads for partial novel PPARγ agonists.

RESULTS:
The natural product honokiol from the traditional Chinese herbal drug Magnolia bark was in silico predicted to bind into the PPARγ ligand binding pocket as dimer. Honokiol indeed directly bound to purified PPARγ ligand-binding domain (LBD) and acted as partial agonist in a PPARγ-mediated luciferase reporter assay. Honokiol was then directly compared to the clinically used full agonist pioglitazone with regard to stimulation of glucose uptake in adipocytes as well as adipogenic differentiation in 3T3-L1 pre-adipocytes and mouse embryonic fibroblasts. While honokiol stimulated basal glucose uptake to a similar extent as pioglitazone, it did not induce adipogenesis in contrast to pioglitazone. In diabetic KKAy mice oral application of honokiol prevented hyperglycemia and suppressed weight gain.

CONCLUSION:
We identified honokiol as a partial non-adipogenic PPARγ agonist in vitro which prevented hyperglycemia and weight gain in vivo.

GENERAL SIGNIFICANCE:
This observed activity profile suggests honokiol as promising new pharmaceutical lead or dietary supplement to combat metabolic disease, and provides a molecular explanation for the use of Magnolia in traditional medicine.

© 2013 Elsevier B.V. All rights reserved.

I'm trialling 200 mg Magnolia extract (90% Honokiol) twice a day.
http://www.swansonvi...L117&csp=SWH225

Edited by blood, 01 October 2013 - 09:24 AM.

[blood]

40-80 mg/day telmisarten for BP reduction gives bonus reduction of visceral fat:

http://www.nature.com/hr/journal/v30/n12/abs/hr2007165a.html

Hypertension Research (2007) 30, 1205–1210; doi:10.1291/hypres.30.1205

Telmisartan Treatment Decreases Visceral Fat Accumulation and Improves Serum Levels of Adiponectin and Vascular Inflammation Markers in Japanese Hypertensive Patients

Daisuke Chujo1, Kunimasa Yagi1, Akimichi Asano1, Hiroaki Muramoto2, Satoko Sakai1, Akitsu Ohnishi1, Miyuki Shintaku-Kubota1, Hiroshi Mabuchi3, Masakazu Yamagishi1 and Junji Kobayashi3

1Department of Internal Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
2Kanazawa Social Insurance Hospital, Kanazawa, Japan
3Department of Lipidology, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan
http://www.nature.co...hr2007165a.html

Correspondence: Junji Kobayashi, M.D., Department of Lipidology, Graduate School of Medical Science, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-8640, Japan. E-mail: junji@med.kanazawa-u.ac.jp

Received 26 March 2007; Accepted 19 July 2007.


Abstract

Hypertension contributes to the occurrence and progression of cardiovascular diseases. The angiotensin II type 1 receptor blocker telmisartan is reported to activate the peroxisome proliferator–activated receptor and improve insulin sensitivity. We investigated the effects of telmisartan treatment on visceral fat, serum adiponectin and vascular inflammation markers in Japanese hypertensive patients. This was an open-label, non-controlled study. Twenty-eight essential hypertensive patients (22 men and 6 women; age 60.61.9 years; body mass index [BMI] 25.50.6 kg/m2) participated. Fat area was assessed with computerized tomography. All the subjects were started on telmisartan 40 mg/day, which was increased to 80 mg/day to achieve the blood pressure target of less than 130/80 mmHg. We assessed the visceral and subcutaneous fat areas, serum adiponectin levels, and vascular inflammation markers at baseline and 24 weeks of telmisartan treatment. There were significant reductions in visceral fat area (from 103.17.9 to 93.38.4 cm2, p<0.01) and pulse wave velocity (from 1,70652 to 1,58751 cm/s, p<0.01) at 24 weeks. In contrast, significant increases in serum high-density lipoprotein cholesterol (from 5.060.15 to 5.320.13 mmol/L, p<0.05) and adiponectin levels (from 8.270.76 to 9.130.81 g/mL, p<0.05) were observed. Also, there were reductions in the interleukin-6 level (from 2.260.27 to 1.600.14 pg/mL, p<0.01). We also conducted these investigations in male subjects alone and similar findings were obtained for all of these parameters. In conclusion, telmisartan treatment was associated with an improvement of vascular inflammation, reductions in visceral fat and increases in serum adiponectin.

Keywords: telmisartan, visceral fat, insulin resistance

[maxwatt]

40-80 mg/day telmisarten for BP reduction gives bonus reduction of visceral fat:

Honokiol (extracted from Magnolia) acts as a PPAR-gamma agonist, but unlike e.g. Pioglitazone doesn't seem to promote weight gain (in mice, at least).

Newish study:

http://www.ncbi.nlm....pubmed/23811337

I'm trialling 200 mg Magnolia extract (90% Honokiol) twice a day.
http://www.swansonvi...L117&csp=SWH225

Telmisartan (Micardis) also lowers blood glucose. Seems to be selective PPARdelta.

Honokiol as Magnolia extract has been used in Asian traditional medicine to treat diabetes. Good find it agonizes PPARdelta. I will be looking into it.

Pioglitazone probably also agonizes PPARalpham which though it also enhances mitochondrial function, leads to adiposity.

[blood]

I'm trialling 200 mg Magnolia extract (90% Honokiol) twice a day.
http://www.swansonvi...L117&csp=SWH225

I think this *might* be assisting with my weight loss.
I've been taking it for around three weeks. No other changes in my supplementation routine. I weigh myself each morning with a fitbit wifi scales so I have weight data for the last few months.
My weight loss over the past two months was at a rate of 0.5 kg/ week.
My weight loss over the past two weeks was at a rate of 1 kg/ week.

[maxwatt]

That is consistent with ppar-delta activation, or it could be chance. Other possible indicators are improvement in exercise tolerance (running or cycling time over a known distance, or on a treadmill or bike ergonometer in a gym) or maybe fasting glucose levels, an indicator of insulin resistance which should diminish with ppar-delta agonism. Fat measuring calipers would provide another possible data-point.

So far your results look good.

[malbecman]

Here is another recent in vivo study of Honokiol.....pretty interesting.

(edit: magnolol is an isomer of honokiol and has been reported to have similar effects).



Mol Nutr Food Res. 2013 Jul 31. doi: 10.1002/mnfr.201300113. [Epub ahead of print]
Long-term supplementation of honokiol and magnolol ameliorates body fat accumulation, insulin resistance, and adipose inflammation in high-fat fed mice.

Kim YJ, Choi MS, Cha BY, Woo JT, Park YB, Kim SR, Jung UJ.

Source

Department of Food Science and Nutrition, Kyungpook National University, Daegu, Republic of Korea.

Abstract


SCOPE:

This study investigated the effect of honokiol (HON) and magnolol (MAG), phenolic compounds in Magnolia plants, on adiposity and adiposity-related metabolic disturbances in mice fed high-fat diet (HFD), and the potential underlying mechanisms focusing on the lipid metabolism and inflammatory response.
METHOD AND RESULTS:

C57BL/6J mice were fed HFD (45 kcal% fat) with or without HON (0.02%, w/w) or MAG (0.02%, w/w) for 16 wk. Despite no changes in body weight, food intake, and hepatic fat accumulation, HON and MAG significantly lowered the weight of white adipose tissue (WAT) as well as adipocyte size and protected against insulin resistance induced by HFD. These effects were associated with increases in energy expenditure and adipose fatty acid oxidation and decreases in fatty acid synthase activity and expression of genes related to fatty acid synthesis, desaturation, and uptake, as well as adipocyte differentiation in WAT. Moreover, HON and MAG significantly lowered the expression of proinflammatory genes in WAT and elevated the plasma IL-10 level. Particularly, HON significantly decreased the plasma resistin level and increased the plasma adiponectin level compared to the control group.
CONCLUSION:

HON and MAG have potential as novel agents for amelioration of adiposity and associated insulin resistance and inflammation.
© 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

KEYWORDS:

Adipogenesis, Antiobesity, Honokiol, Inflammation, Magnolol

PMID: 23901038

Edited by maxwatt, 22 October 2013 - 03:00 AM.

[blood]

That is consistent with ppar-delta activation, or it could be chance.

Just to complicate things, I have observed in myself some distinct psychological/ cognitive effects with honokiol supplementation.
When I first started taking it, I experienced a mild nausea for the first few days (reminded me of starting an SSRI regimen).
I also noticed an anti-anxiety effect (I expected I would notice something like this, based on reports from others).
After a few days, I noticed what I would describe as an increase in motivation/ ambition (this was an unexpected effect).
There are studies showing that honokiol has antidepressant effects (in mouse models of depression - no human studies apparently).
I should mention that I am taking Effexor for depression (or, to prevent a relapse of depression). I don't consider myself to be depressed at the moment, but who knows. Maybe I am experiencing an antidepressant effect from the honokiol.
So if honokiol is contributing to my weight loss, it could be partly through an antidepressant effect, leading to increased motivation to stick with my diet plan and exercise (in addition to any possible direct effects on adipose tissue). Unfortunately I haven't been recording my diet over the last month.

Other possible indicators are improvement in exercise tolerance (running or cycling time over a known distance, or on a treadmill or bike ergonometer in a gym) or maybe fasting glucose levels, an indicator of insulin resistance which should diminish with ppar-delta agonism. Fat measuring calipers would provide another possible data-point.

I am using a fitbit scales to measure body fat. (I know this is likely not super accurate, I'll get a DEXA scan at some point). In the last few days, I've dropped to 16.1% body fat - the lowest it's been. I've been stuck at 17-18% for many, many months. If I can get to 15% I will be stunned. I've noticed my lower body (thighs area) is looking distinctly more wiry.

Do you have a recommendation for a glucose measuring device? I've been wanting to start tracking glucose - just not sure what to use.

Edited by blood, 22 October 2013 - 02:27 AM.

[maxwatt]

Do you have a recommendation for a glucose measuring device? I've been wanting to start tracking glucose - just not sure what to use.

Truetrack and Trueresult are two brands sold under the house label of drugstores such as Walgreens and CVS. Truetrack is cheaper, maybe a little more accurate, Trueresult is easier to use and requires less blood. Both are good enough for tracking changes, and give results in about 10 seconds.