Saturday, December 29, 2012

Yohimbine & Berberine Protect From Death Due to LPS Intoxication; BCAAs Inhibit Serotonin Metabolism & Cause Anxiety, Tryptophan but not SSRIs Help; Sweet Tea Leaves Are PPAR-G Antagonists & Battle High Lipid + Leptin Levels

Skip the fireworks invest the money in some quality ingredients for a fondue or whatever you like and invest the (often non-negligible) rest of the money in a gym membership for the next year.
Actually my figure of the week is 115,000,000 EUR (~152,000,000 US Dollar), which is the sum my fellow country men and women are about to waste on pyrotechnics this year. And a scientifically unconfirmed addition based on my personal observation: 90% of the worst offenders as far as spending money for fireworks goes are at least overweight. Would be interesting to see, if the use of pyrotechnics on New Years Eve is directly associated with fat mass...

I mean, it could be that they spent so much money on their fireworks that they feel they can only afford the junkfood of which everybody and his/her mama still tend to believe that it would be cheaper than buying fresh products and preparing your own food from those.

Ah, I am ranting. That's usually Carl Lanore's task, so I will better go on with the items I have compiled for the today's last installment of On Short Notice in the year 2012:
  • Berberine + yohimbine - a synergistic duo to prevent LPS toxicity (Li. 2012) -- With all the recent hoopla about the gut microbiome, I suppose that I don't have to tell you what the acronym LPS stands for, right? Hmm... just to make sure it stands for lipopolysaccharide endotoxins which are produced by gram negative bacteria in your gut and are so "toxic" (in fact they cause profound inflammation) that they can be lethal at higher doses.

    Figure 1: Survival rates (%) after ALB/c mice LPS injection (Li. 2012)
    A group of Chinese scientists have now found that aside from berberine the anti-inflammatory effects of which have been known for quite some time now, yohimbine administered in a daily dose of 2mg/kg (human equivalent 0.16mg/kg) does add to the survival rate of berberine treated rodents (human equivalent 4mg/kg) that were injected intragastrically (so not directly into the blood) with a potentially lethal dosage of 20mg/kg LPS. What's more, taken on its own yohimbine is even more potent than the alkaloid that's found in such plants as Berberis aquifolium, Oregon grape, Berberis vulgaris, Berberis aristata, Hydrastis canadensis (goldenseal), Phellodendron amurense, Coptis chinensis and Tinospora cordifolia.

    The mechanism is mediated by the prevention of liver injury, an upregulating of IL-10 production (an anti-inflammatory cytokine), and related anti-inflammatory effects resulting from the suppression of phosphorylation of IkBa, JNK, ERK and IRF3 in macrophages.

  • Chronic 9-week high BCAA diet impairs brain tryptophan levels and causes anxiety (Coppola. 2012) -- Scientists from the Duke University took another look at the BCAA-tryptophan depression connection, you may have read about in the context of my "Sugar Addicted or Just Stressed Out?" post from January 3, 2012.

    According to the results Anna Coppola and her colleagues are about to publish in the American Journal of Physiology  - Endocrinololgy and Metabolism the provision of a BCAA-enriched diet for 9 weeks leads to both reductions in brain tryptophan levels and an increased turnover of serotonin (5-HT) in rodent brains:
    Figure 2: Composition of low fat  (LF) and high fat (HF) diets with or without added BCAAs (left); effects on the ratio of tryptophan  to the molar sum of large neutral amino acids with and without supplemental  tryptophan in the drinking water and 5HT turnover in the brain (no supplemental trp, right; Coppola. 2012)
    Both groups (BCAA and non-BCAA) consumed about identical amounts of food as the rodents in the complementary (LF or HF) groups, which confirms that the BCAA content did not modify the taste of the chow or rendered it unpalatable (cannot have been cheap bulk powder then ;-). The reduction in both the availability of tryptophan as well as the increase in serotonin (5-HT) turnover in the brain must in fact have been a consequence of the added BCAAs and are most likely the root of the disrupted transport of tryptophan across the BBB in rats, leading to reduced exploratory behavior of rats in EPM testing, a sign of increased anxiety.
    "Recent studies demonstrating a strong  association between BCAA levels, obesity, and obesity-related metabolic disorders, when linked to the findings reported here, may help to explain the strong association between obesity and behavioral abnormalities, including depression and anxiety." (Coppola. 2012)
    As the slight differences between the high an low carb diets show, other nutrients can influence serotonin as well (read more)
    In this regard it is important to point out that these negative side effects were mostly reversible by the provision of 15 mg/100 ml tryptophan in the drinking water of the rodents, but were not alleviated by  the administration of the common serotonine reuptake inhibitor fluoxetine (at 10 mg/kg/day for four weeks).

    Bottom line: Isolation is not what you want if what your body has been build for is complex food. And while the single serving of BCAAs you may gulp down during or right before a workout, on the other hand, probably isn't going to harm you. The "I need BCAAs every 30min" approach to gaining muscle mass, may well turn you into a psychotic wrack if you follow it day in and day out for months or years - at least without chronically adding some l-tryptophan to the equation.

  • Sweet tea leaves protect against obesity: Once more via PPAR-gamma blockade (Zhou. 2012) -- Actually this is probably not news to anyone out there with a degree in Traditional Chinese medicine. After all, Lithocarpus polystachyus Rehd.(Sweet Tea) is Chinese folkloric medicine that has always been used to treat obesity, diabetes, and hypertension in South China:
    "Previous experiments revealed that it contains plentiful bioactive flavonoids and polyphenolic compounds, e.g. phlorizin, trilobatin, 3-hydroxy-phlorizin, etc. These components have extensive pharmacological activities, such as anti-diabetes, memory improvement, anti-aging, inhibition of lipid peroxidation and the growth of human colon cancer cells, and so on." (Zhang. 2012)
    From a "scientific" perspective, however, the efficacy of this herbal medicine as an obesity treatment had still to be elucidated.
    Figure 4: Effects of oral gavage of 75 mg, 150 mg and 300 mg/kg of body weight/day of sweet tea extract or placebo (DIO) in conjunction with the 8 weeks on a obesogenic diet (Zhang. 2012)
    In this context it is yet worth mentioning that this study demonstrated for the first time that the aqueous dry leaves extract of Lithocarpus polystachyus Rehd. can potently reduce the worst metabolic side effects of obesity, such as the hypolipidemia, hypoleptinaemia and the degree of insulin resistance (FINS, HOMA-IR, cf. figure 3) what it does not answer, however, is whether the decline in PPAR-gamma is tissue specific, what exactly is behind the profound decline in leptin levels and whether or not lean rodents, let alone humans, who don't consume an obesogenic diet will see anywhere similar benefits.

    In other words, this is research in progress, but I suppose something you are going to hear more about at the Supppversity in 2013.
* * * * * *

Apropos hearing or rather reading more, I guess you will realize that you have reached the end of today's installment of On Short Notice which means that you will have to progress to the SuppVersity Facebook Wall if you want a second serving of news on...
  • The history of vitamin A as a light sensor and beyond - actually a free full-text I guess those of you who like to "think paleo" may enjoy (read more)
  • A paper on "good" and "bad" inflammation, where the author points out that soothing inflammation too much can lead to a reduction in energy expenditure and may therefore not be the king's road to getting rid of the last blubber (read more)
  • The food-hitlist of young Americans - Featuring sugar, sugary drinks, sugary bakery, sugary ... as their main energy and carbohydrate sources... (read more)
  • Problems with synthroid and generics that have surfaced in a recent study on their efficacy in the treatment of congenital hypothyrodism (read more)
as well as a handful of other news, which are already there or are going to be posted within the next hours. Have a great weekend, everyone! 

  • Coppola A, Wenner BR, Ilkayeva O, Stevens RD, Maggioni M, Slotkin TA, Levin ED, Newgard CB. Branched-chain amino acids alter neurobehavioral function in rats. Am J Physiol Endocrinol Metab. 2012 Dec 18.
  • Li H, Wang Y, Zhang H, Jia B, Wang D, et al. Yohimbine Enhances Protection of Berberine against LPS-Induced Mouse Lethality through Multiple Mechanisms. PLoS ONE. 2012; 7(12): e52863. 
  • Zhou CJ, Huang S, Liu JQ, Qiu SQ, Xie FY, Song HP, Li YS, Hou SZ, Lai XP. Sweet tea leaves extract improves leptin resistance in diet-induced obese rats. J Ethnopharmacol. 2013 Jan 9;145(1):386-92.


  1. This post and others on your site refer to the importance of a protein rich diet but you also mention Creatine and EAA/BCAAs regularly.
    I appreciate that a lot of factors will depend on how an individual might supplement these in their diet but I was wondering whether you have any view or know where I could find guidance on the best/most effective dosage?

    1. Most effective dosage for what?

    2. good question: I can certainly tell you that the most healthy diet is one where you don't use much protein to derive energy from it. Which equates to "eat enough carbs and fat" as your fuel source. You will notice that ALL the scientifically "benefits from high protein diets" are usually achieved with <=40% of the energy coming from protein.

    3. Dosage for EAAs and BCAAs. Also I would be interested to know the dosage for Creatine too. Thank you

    4. But what are you using them for? Pre-workout? What? It matters.

      As for creatine, 20g/day for a week followed by 3-5g/day, or just 3-5g/day for a month. Either way saturation will occur and then you just continue the 3-5g/day to maintain.

    5. Using them to build muscle - I've seen elsewhere that they can be taken pre workout and post workout. I was hoping to take a daily amount for consistency - but perhaps there is a better way?

    6. Eat 1-1.5 g/lb. lean body mass of protein daily. Set fat at 50g/day or 25% of Calories, whichever is higher. Remainder carbs. BCAAs are unneeded and a waste of money with the only exception being if you workout fasted. In that case take 10g 10-20 minutes pre-workout.

    7. Would this be different if I was trying to improve the amount of energy I have. I was thinking of using Creatine, BCAAs and Acetyl-L-carnitine to improve my energy levels. Sorry for jumping around but it's very interesting to hear your views.

    8. I suppose when you mean energy levels you mean your training performance? If so, BCAAs can help but IMHO they are not worth it due to the negative effects they might have on your well being and mental health.
      ALCAR and creatine are good choices though. If you are looking for an energy boost you might want to consider tyrosine and/or NADH.

  2. Excellent post, well done for highlighting the BCAA craze. I've been preaching about the rather serious side effects to those willing to listen for a long time but hey, nothing builds muscle bettere than 30gms of BCAA every 4 hours haha. I remember our discussion in the sugar addicted post, I was wondering what your thoughts are on BCAA induced prolactin increase and impaired functioning of the decision making process. I guess that the chances of that happening are slim IF the diet is not (over)abundant in protein. Let us not forget that serotonin is just a part of the picture as dopamine takes a hit too with BCAA supplementation.
    Personally, I have cut out all protein powders, bcaa, eaa and just rely on my diet to meet my protein requirements, which appear to be much lower than I previously thought. I dropped from 250 to 200 and then subsequently 150-170 and feel much better- depression and anxiety is all gone.

    1. as far as dopamine is concerned the study at hand did show a minimal reduction in tyrosine, but nothing that would suggest that it was likewise whacked. That could be different with other baseline diets and higher BCAA intakes, though.

      As far as prolactin is concerned, I would have to dig deeper, but out of my head I remember that it BCAAs are actually used to lower prolactin in patients with hepatic encephalopathy. I would therefore be surprised if it had the exact opposite effects in healthy people. Also because high 5HT = high prolactin.

    2. Re BCAAs and prolactin I am quite sure that they elevate prolactin. BCAAs are used in stuttering patients in order to decrease their dopamine levels. There's a negative correlation betweeen dopamine and prolactin so if BCAAs lower dopamine (and apparently they do), they will also cause a spike in prolactin.
      "Compared to placebo, the BCAA mixture increased prolactin levels and impaired IGT performance. "
      So it looks like BCAA mess up both your dopamine and serotonin levels. Yikes!

  3. Doc, you confused Zhou with Zhang, both sweet leaf references should be Zhou 2013. Great study BTW.