Showing posts with label n-acetyl-cystein. Show all posts
Showing posts with label n-acetyl-cystein. Show all posts

Saturday, February 9, 2013

Fat From Serotonin, MS Despite Vitamin D, DHA & DPA in Your Cell Walls. Weightloss Obstacle Late Lunch?

Yet another reason why calorie counting is not good for your sanity: The "average" sexual intercourse burns only 14 kcal more than watching TV.  and significantly less than a fast paced walk on the inclined treadmill. Luckily weight loss & maintenance is more complex than calories in vs. out, anyway ;-)
"14" that's the SuppVersity figure of the number of extra calories you will expend when you and your significant other decide to have sex instead of sitting on the couch watching TV tonight. I got that figure from a paper my buddy Sean Casey from CasePerformance has brought to my attention. Published in the latest issue of the prestigious New England Journal of Medicine (Casazza. 2013), it discusses the 7 most commonly held "false and scientifically unsupported beliefs about obesity" the scientists identified in a thorough analysis of popular media and scientific literature.

"The scientific community needs some more honesty"

While the sex-myth, which originally states that you would burn at least 100kcal, with a little more action" even 300kcal per intercourse, is obviously my favorite, there are also a couple of  less sexy "presumptions about obesity" (e.g. simply eat more veggies and fruit and you lose weight) and "facts about obesity" (e.g.  the scientists dug up and debunked in a paper that ends with the wise words:
"While we work to generate additional useful knowledge, we may in some cases justifiably move forward with hypothesized, but not proved, strategies. However, as a scientific community we must always be open and honest with the public about the state of our knowledge and should rigorously evaluate unproved strategies." (Casazza. 2013)
Actually the term "the state of our knowledge" is an ideal segue to what follows - the "short" news! Originally the On Short Notice column was actually intended as a very brief overview of what has been going on in the "community" as of late. And since we are talking about honesty, I must admit that I have failed miserably in the past installments as far as the tiny word "short" in the column's title is concerned.

The new short news are short again ;-)

So, as of now, I will be doing my very best to bring the On Short Notice column back on the short track, so to say. I guess, we will see in a couple of paragraphs, how successful my efforts will be ;-)
  • Does serotonin make you fat? It's pro-fat storage effects would suggest so

    If 5-HT can make you fat and creatine blunts its increase PWO (learn more), what does that tell us about creatine? Nothing, but it leaves room for speculations.
    (Gres. 2013) -- If you trust in TV wisdom the reason women eat chocolate, whenever they feel sad or alone is it's ability to boost serotonin (5-HT). The latter is yet not the reason Sandra Grès et al. say that serotonin could make you fat. Rather than that, it's the ability of 5-HT to stimulate the obesogenic peroxisome proliferator-activated receptor γ (PPAR-γ, learn more), on adipose cells, which will increase fat storage and the recruitment of new fat cells from the stem cell reservoir.

    These effects happen in the periphery (vs. the brain) and are totally unrelated to the centrally mediated effects of serotonin.
  • MS patients benefit from the sun, not vitamin D

    (Zivadinov. 2013) -- Where is your vitamin D supposed to come from? From your skin, right. And where does your skin get it from? From tablets? No. It manufactures it from the "bad" cholesterol when it's  exposed to the "bad" sunlight.

    In the upper left of this image you see, where the magic is - the rest is just a nice bonus.
    With all those supposedly bad, but in fact, vital things being important for much more than vitamin D synthesis it is therefore not surprising that a recently published paper on the associations of sun-exposure and/or vitamin D with MRI measures in multiple-sclerosis patterns revealed that
    "[...] sun exposure was associated with increased grey matter volume (GMV, rp=0.16, p=0.019) and whole brain volume (WBV, rp=0.20, p=0.004)" (Zivadinov. 2013).
    ...and that totally irrespective of whether the subjects had high or low vitamin D levels. If you wanted to say it fancily, you'd say the beneficial effects of sun exposure on the brain volume in MS patients was found to be disassociated from the effect the sun has on vitamin D levels (suggested read: Vitamin D, Epstein Bar & MS)
  • If you want to up the omega-3 levels in your tissue, pick DHA and / or its precursor DPA over EPA

    Figure 1: Incorporation various lipid fractions in different tissues (Kaur. 2013)
    (Kaur. 2013) -- According to a very recent rodent study docosahexaenoic acid (DHA) and docosapentaenoic acid (DPA) are much more readily incorporated into two of your most vital organs, namely your brain and liver and likewise the preferred phospholipid in the cell walls of your kidneys and muscle tissue. Only your fat cells don't really like these long(est) chain omega-3s the incorporation of which was ~50% lower than that of oleic acid (OA; that's the mono-unsaturated fatty acid in olive oil), which was used as a "neutral" control.

    The one question I would still like to have an answer to is how beneficial it actually is if the phospholipids (PL, figure 1) in your cell membranes are full of easily oxidizable fatty acids.

    Also, what do we make of the other lipid fractions? Cholesterol (CHOL), diacylglycerol (DGL) and NEFAs + triglycerides (NE+TG)? Where do we actually want those good omega-3 fatty acids to accumulate? ... just some food for thought for your DPA and DHA lovin' brains ;-)
  • On a side note: If you like GMO, you won't have to eat fish any longer to get your omega-3 PUFAs

    (Petrie. 2012) -- Researchers from the CSIRO Food Futures National Research Flagship have already engineered the first GMO brassica species with a higher DHA yield >11% than fish. The invention is hailed as "a breakthrough in the development of sustainable alternative sources of DHA as this technology should be applicable in oilseed crops" (Petrie. 2012)
  • When late eating (spec. lunch) and certain genes come together weight loss can become pretty difficult - reasons still not fully understood, though

    (Garaulet. 2013) -- Late lunch and certain genotypes appear to make weight loss difficult for some. And the relation holds even after possible confounding factors like energy intake and even appetite hormones, were measured.
    Skipping breakfast. Yay or Nay? (read more)
    "Late lunch eaters lost less weight and displayed a slower weight-loss rate during the 20 weeks of treatment than early eaters (P=0.002). Surprisingly, energy intake, dietary composition, estimated energy expenditure, appetite hormones and sleep duration was similar between both groups." (Garaulet. 2013)
    While this is not a general argument against intermittent fasting, skipping breakfast and the like, it does still go to show you that we are not all created exactly equal and any cookie cutter approach to weight loss, therefore, counter-indicated. 
  • Show me your wrist and I'll tell you something about your glucose metabolism.

    (Nudeh. 2013) -- A study that was published in the latest issue of the The Journal of Clinical Endocrinology & Metabolism reveals: Wrist circumference is a significant predictor of diabetes in both genders of the adult population.
    Figure 2: Incidence of diabetes during 8.8 years of follow-up in different tertiles of baseline
    wrist circumference among male and female populations (significant trend in both genders; Noudeh. 2013)
    What's particularly interesting is that this association which was observed in a cohort of 6393 subjects (2716 males and 3677 females), who had been subjected to a standard 2-hour post challenge plasma glucose, test holds independent of BMI and waist circumference - allegedly for women, only. 
  • Sildenafil Citrate Attenuates the Deleterious Effects of Elevated Ammonia

    (Arafa. 2013) -- You will probably remember the problems with ammonia accumulation due to huge BCAA and protein intakes (learn more). If you trust the latest results of two Egyptian researchers from the Zagazi University it would look as if a solution to that problem (which shouldn't be one, if your liver is healthy and you don't go overboard on pro-ammonia foods, anyway) would already exist: Sildenafil citrate aka Viagra can help.

    In their study, the researcher administered 10mg/kg sildenafil to rats that were treated with a daily intraperitoneal (i.p.) injection of ammonium chloride (100 mg/kg body weight) for eight weeks. This treatment resulted in a significant reduction in serum liver enzymes, lipid profile and - maybe most importantly - brain lipid peroxidation and caspase-3 mRNA. It also increased the nitric oxide (NO) levels in the blood and lead to a significant increase in cGMP, antioxidants and endothelial nitric oxide synthase (eNOS) gene expression in the brains of hyperammonemic rats.
    List of various foods and their ammonia content (Rudnan. 1973)
    "Our results showed that sildenafil exerts a protective effect on the brain by reversing oxidative stress during hyperammonemia and this could be due to (i) cytoprotective, antioxidant and anti-apoptotic effects ii) increasing cGMP and enhancing the proper metabolism of fats which could suppress oxygen radical generation and thus preventing oxidative damage in the brain."
    Until now, the scientists cannot tell how exactly the human equivalent of 1.62mg/kg sildenafil citrate work, but its modulatory effect on the NO/cGMP pathway is the most likely candidate. That these effects are of real world significance has incidentally been shown, already. In 2003, for example, the learning abilities of rats with hyperammonemia was restored by a similar regimen (Erceg. 2003) 
  • Acetyl cysteine - don't swallow, but rub it... onto your skin, if you have acne

    (
    The comedo count is a measure of the number of comedones, i.e. the open black "pores" like those on the forehead of the person shown on this photo
    Montes. 2012) -- According to a study published in the latest issue of Skinmed, the application of a 5% acetylcysteine topical gel proved to be "significantly superior to placebo (P = .04)" in reducing the comedo counts. The results were comparable in male and female participants and would suggest that "acetylcysteine is an effective therapeutic option for the treatment of mild to moderate acne". Whether it is an alternative to the retinoid based standard drugs, is yet still questionable.

    By the way, the latter, or rather the most prescribed of these retinol-like drugs, namely tretinoin has only recently been found to synergize with Aloe vera for even better results (Saeedi. 2013).
  • Brazilian propolis ethanol extract promotes glucose uptake and translocation of insulin-sensitive glucose transporter (GLUT) 4 in skeletal muscle
     
    In the unfortunate case, you missed the news: The commonly ignored BCAA Isoleucine also boosts GLUT4 (read more)
    (Ueda. 2013) I guess you will have heard about the miracles "royal jelly" is supposed to work on your health, right? Well, the cheap "packaging" material bees use to seal the smaller gaps in their hives (the larger ones are usually filled with beeswax) seems to have similarly outstanding - and in this case scientifically backed effects.

    When propolis was administered at a human equivalent dose of 20mg/kg to mice, those rodents saw increases in both PI3 and AMPK modulated increase in the glucose transporter 4 activity and skeletal glucose uptake.

    The main active polyphenols were artepillin C, coumaric acid, and kaempferide. All of them promoted GLUT4 translocation in a subsequent ex-vivo analysis using L6 myotubes, but kaempferide, which can also be found in avocado seeds (Pahua-Ramos. 2012) and cardia sinensis aka grey-leaved saucer berry extracts (Martinetti. 2010), was the most potent one.
Now you are surprised, right? Me too. Nine individual items and all of them still qualify as "short news". I guess in view of the sheer abundance of news you won't need anything else till tomorrow, but in case you do, I have a couple of suggestions to check out on the SuppVersity Facebook Wall:
  • Lycopene works as an anti-cancer agent, because some of it's metabolites "look" like retinol (vitamin A) and dock to the retinol receptor (read more)
  • Curcumin is a hormetic agent (learn more about hormesis), but not all curcuminoids are created equally effective (read more)
  • White poison!? Low sugar diet does not improve insulin sensitivity but decreases glucose levels in obese subjects (read more)
  • Myostatin knockout mice have increased brown fat - Does this mean that myostatin suppression will increase browning of fat in man, as well? The recent SuppVersity article on PGC-1A4 already confirmed that (read more
  • Fish oil for alcohol withdrawal - Only three weeks on low dose EPA (60 mg/day) and high dose DHA (252 mg/day) supplement yielded significant decreases in distress symptoms and basal cortisol secretion in abstinent alcoholics (read more)
  • SuppVersity Suggested Read: The Hunter-Gatherer Within: Health and the Natural Human Diet - "Don't get your food from the same place your car does" (read more)
There are going to be a couple of more news before the official next SuppVersity post will be posted in ~24h - so "like" the SuppVersity on Facebook and make sure you don't miss any of them. Have a nice weekend!

References:
  • Arafa MH, Atteia HH. Sildenafil Citrate Attenuates the Deleterious Effects of Elevated Ammonia. Toxicol Mech Methods. 2013 Jan 23. 
  • Casazza K, Fontaine KR, Astrup A, Birch LL, Brown AW, Bohan Brown MM, Durant N, Dutton G, Foster EM, Heymsfield SB, McIver K, Mehta T, Menachemi N, Newby PK, Pate R, Rolls BJ, Sen B, Smith DL Jr, Thomas DM, Allison DB. Myths, presumptions, and facts about obesity. N Engl J Med. 2013 Jan 31;368(5):446-54.
  • Erceg S, Monfort P, Hernández-Viadel M, Rodrigo R, Montoliu C, Felipo V. Oral administration of sildenafil restores learning ability in rats with hyperammonemia and with portacaval shunts. Hepatology. 2005 Feb;41(2):299-306.
  • Garaulet M, Gómez-Abellán P, Alburquerque-Béjar JJ, Lee YC, Ordovás JM, Scheer FA. Timing of food intake predicts weight loss effectiveness. Int J Obes (Lond). 2013 Jan 29.
  • Grès S, Canteiro S, Mercader J, Carpéné C. Oxidation of high doses of serotonin favors lipid accumulation in mouse and human fat cells. Mol Nutr Food Res. 2013 Feb 6.
  • Jahangiri Noudeh Y, Hadaegh F, Vatankhah N, Momenan AA, Saadat N, Khalili D, Azizi F. Wrist Circumference as a Novel Predictor of Diabetes and Prediabetes: Results of Cross-Sectional and 8.8-Year Follow-up Studies. J Clin Endocrinol Metab. 2013 Feb;98(2):777-84.
  • Kaur G, Molero JC, Weisinger HS, Sinclair AJ. Orally administered [14C]DPA and [14C]DHA are metabolised differently to [14C]EPA in rats. British Journal of Nutrition. 2013; 109, pp 441-448. 
  • Martineti V, Tognarini I, Azzari C, Carbonell Sala S, Clematis F, Dolci M, Lanzotti V, Tonelli F, Brandi ML, Curir P. Inhibition of in vitro growth and arrest in the G0/G1 phase of HCT8 line human colon cancer cells by kaempferide triglycoside from Dianthus caryophyllus. Phytother Res. 2010 Sep;24(9):1302-8.
  • Montes LF, Wilborn WH, Montes CM. Topical acne treatment with acetylcysteine: clinical and experimental effects. Skinmed. 2012 Nov-Dec;10(6):348-51.
  • Pahua-Ramos ME, Ortiz-Moreno A, Chamorro-Cevallos G, Hernández-Navarro MD, Garduño-Siciliano L, Necoechea-Mondragón H, Hernández-Ortega M. Hypolipidemic effect of avocado (Persea americana Mill) seed in a hypercholesterolemic mouse model. Plant Foods Hum Nutr. 2012 Mar;67(1):10-6.
  • Petrie JR, Shrestha P, Zhou XR, Mansour MP, Liu Q, Belide S, Nichols PD, Singh SP. Metabolic engineering plant seeds with fish oil-like levels of DHA. PLoS One. 2012;7(11):e49165. 
  • Rudnan D, Smith RB 3rd, Salam AA, Warren WD, Galambos JT, Wenger J. Ammonia content of food. Am J Clin Nutr. 1973 May;26(5):487-90.
  • Ueda M, Hayashibara K, Ashida H. Propolis extract promotes translocation of glucose transporter 4 and glucose uptake through both PI3K- and AMPK-dependent pathways in skeletal muscle. Biofactors. 2013 Jan 28.
  • Zivadinov R, Treu CN, Weinstock-Guttman B, Turner C, Bergsland N, O'Connor K, Dwyer MG, Carl E, Ramasamy DP, Qu J, Ramanathan M. Interdependence and contributions of sun exposure and vitamin D to MRI measures in multiple sclerosis. J Neurol Neurosurg Psychiatry. 2013 Feb 5.

Saturday, September 24, 2011

Mitohormesis - Suffocated Mitochondria Live Longer: Scientists Probe Longevity-Effect of Low-Level Stressors.

Image 1: Walter Breuning died in April 2011at the biblical age of 114! And you bet that a man who has seen two world wars has had his share of mitohormetic stress in his life.
As a diligent reader of the SuppVersity you will be familiar with the work of S. Schmeisser and M. Ristow from the Department of Human Nutrition at the University of Jena, here in good old Germany (where not everyone eats Sauerkraut und Weisswurst, even now that the Oktoberfest is in full swing). In previous publications, the scientists have (at least in my mind conclusively) argued against the publicly accepted free-radical hypothesis of aging, which implies that the presence of free radicals is one of the fundamental mechanisms of aging. Now, a few month after the publication of their last review back in May 2011, they are presenting the latest results from their own lab in a paper that is going to be published in the October issue of Hormone and Metabolic Research (Schmeisser. 2011).

Want to live longer? Then you better put another log on the fire

Schmeisser, Zarse, and Ristow used lonidamine (LND), a indazole-3-carboxylic acid derivate, to inhibit cellular respiration in the infamous round-worm (Caenorhabditis elegans) model for aging processes (for a review on the pharmacology, biochemistry and toxicology of lonidamine see Silvestrini. 2008). In essence, they thusly made it more difficult for the cells to "breath", which as you may probably imagine, is a major stressor, which will inevitably increase the formation of purportedly dangerous free radicals (ROS) and should thus increase the aging process, if... yes, if there was any truth to the nonsensical idea that you better sit there, don't eat, don't drink, don't move - in essence - don't live to avoid any potential ROS formation, if you want to extend your lifespan... I guess, you as a self-educated SuppVersity reader won't be surprised that the roundworms did not only survive the "torture" (of life), but - after an initial mitohormetic response, i.e. an adaptational response to the the scientists' effort to suffocate their mitochondria (the initial reduction in oxygen consumption was -37 %!) - thrived on the purportedly life-shortening inhibitor of mitochondrial respiration!
Figure 1: Lifespan of C. elegans treated with 5µM lonidamine, n-acetyl-L-cysteine (NAC) or both (data calculated based on (Schmeisser. 2011)
As you can see in figure 1, the "pro-oxidant" treatment with lonidamine, of which Schmeisser's, Zarse's and Ristow's data shows that it increased respiration and thus mitochodrial ROS formation, increased both median as well as maximal life-expectancy of the nematodes (roundworms) by ~8% - an increase with statistical significance, as the p-value of p<0.001 (= chances that the increased lifespan observed in the study is just coincidence are <0.1%). The latter cannot be said of either the slight increase in maximal lifespan nor the slight decrease in median lifespan in the group of nematodes that was treaded with n-acetyl-L-cysteine (p=0.17; non-significant) or a combination of the anti-oxidant sulfur-amino acid and lonidamine (p=0.95; absolutely non-significant; cf. figure 1).

These observations may be considered further experimental "evidence" for Schmeisser's and Ristow's previously formulated mitohormesis theory ("evidence" in the sense that the results do not falsify their hypothesis - they do yet falsify the ROS hypothesis of aging). A theory that refutes the idea that the aging process is driven by reactive oxygen species and emphasizes (mitochondrial) adaptation processes to (external) stressors that strengthen, not weaken the organism in the long-run - or as the scientists phrase it:
[...] the induction of endogenous defense mechanisms as a secondary response to a stressful condition is assumed to contribute to longevity [...] a lifetime low dose oxidative stress with a subsequent secondary induction of defense mechanisms could delay the aging process
It is thus the interplay of manageable stress and metabolic adaptation which extends life and not an overall reduction of reactive oxygen species, as the vendors of some "super-potent" anti-oxidants would have you believe. What is still missing though, is a tool which would help us to identify the critical point, where the endogenous adaptation processes cannot keep pace with ever-increasing (mainly) exogenous stressors... in case any scientist finds an answer, I guess you will soon be able to download the respective app on your shiny new iPhone - I just hope that this app will account for the significantly (!) decreased glucose metabolism the iPhone itself will induce in the temporoparietal junction and anterior temporal lobe of the right hemisphere of your brain within less than 30 minutes (Kwon. 2011), as well.

Thursday, July 7, 2011

Amino Acids for Super Humans. Part IV: Purported Ergogenics - Beta Alanine, Carnitine, Glutamine

This relevant for all of you - regardless of whether you can or cannot spare the time: Tune in live and listen to me @ Carl Lenore's Super Human Radio to learn that amino acids are far more than just the building blocks of the proteins of your body...

Listen live to SHR @ 12:00PM ET
Amino Acids for Super Humans. Part IV
Purported Ergogenics - Beta Alanine, Carnitine, Glutamine

In the fourth installment of the show, we are going to look at three of those amino acids everyone interested in fitness and body building knows: Beta Alanine, Carnitine and Glutamine. Will the increase performance, fat loss and muscle gains, as some supplement companies would have it, or will they mostly cost your hard earned money or even make you sick? Tune in live @ 1pm ET and learn more!

Monday, June 20, 2011

Show Notes: Amino Acids for Super Humans. Part III - Sulfur, More Than Just Rotten Eggs.

Amino Acids for Super Humans. Part III
Sulfur, More Than Just Rotten Eggs

notice! this are 100% uncorrected show notes not originally intended for publication

In this episode we are going to tackle:
  • methionine (essential amino acid, EAA)
  • cysteine (conditionally essential amino acid)
  • n-acetyl cysteine (acetylated variety of cysteine, not found in food sources)
  • taurine (non-essential amino acid)

Thursday, June 9, 2011

Amino Acids for Super Humans. Part III - Sulfur, More Than Just Rotten Eggs.

This relevant for all of you - regardless of whether you can or cannot spare the time: Tune in live and listen to me @ Carl Lenore's Super Human Radio to learn that amino acids are far more than just the building blocks of the proteins of your body...

Listen live to SHR @ 12:00PM ET
Amino Acids for Super Humans. Part III
Sulfur, More Than Just Rotten Eggs
update: Episode available for download, now!

In the third installment of the show, we are going to look at the commonly overlooked. yet vitally important sulfur-containing amino acid methionine, its "children" and "grand children", cysteine, n-acetyl-cysteine (NAC) and the purported "cell volumizer" taurine.

As usual, I will do my best to provide relevant examples and relate the theory to practical advice. The magic of individual amino acids will be tackled in the shows to come.

Wednesday, January 19, 2011

Reactive Oxygen Specimen (ROS) Trigger Muscle Hypertrophy via IGF-1 Signaling

I have touched on the "usefulness" of oxidation, only yesterday. Now, a very recent study appears to confirm the notion that a controlled amount of inflammation is necessary in order to achieve metabolic and muscular adaptations.
Figure 1: Eesult of the quantitative analysis of myotube diameter after IGF-I and NAC treatment (Handayaningsih. 2011)
Scientists from Division of Diabetes and Endocrinology and Division of Cellular and Molecular Medicine at the Kobe University Graduate School of Medicine published a paper (Handayaningsih. 2011) describing an investigation into the role of Reactive Oxygen Specimen (ROS) in the IGF1-signaling pathway. In this study N-Acetyl-Cystein (NAC), commonly used by recreational athletes as an "ergogenic" aid, blunted myocyte response to IGF1 and thus inhibited muscle hypertophy (cf. Figure 1):
While treatment with H2O2 significantly enhanced IGF-I-induced phosphorylation of the IGF-I receptor (IGF-IR), IGF-IR phosphorylation was markedly attenuated when cells were treated with antioxidants. The downstream signaling pathway, Akt-mTOR-p70S6K was subsequently down-regulated. Furthermore, thephosphorylationof FoxO1by IGF-I decreased concomitantly with the restoration of the expression of its target genes, Atrogin-1 and muscle RING finger 1, which are related to muscle atrophy.
Before you now go and flush all your vitamins and antioxidants down the toilette, you should consider that this is an in-vitro study with a narrow and limited ROS stimulation and not a large scale exercise supplementation study showing that the 500-1.000 mg of NAC you take on a daily basis will completely forestall muscle growth. If anything, it should remind you that excessive "inflammation" could be the "root of all evil" (cf. Super Human Radio), but excessive antioxidant supplementation certainly ain't a solution.