Saturday, October 27, 2012

Reishi Protects Against Cancer & Contains Anti-Androgen; Adrenalin Rejuvenates Brown Fat; Mild Stress Normalizes Cortisol / DHEA Ratio in Elderly; DHEA, Aromatase Inhibitors & BPA vs. Joint & Brain Health; Vitamin E Battles Lymphoma

I am not happy with how the short news on Facebook simply disappear into oblivion.
The SuppVersity figure of the week is "920"! "920" as in "920 published posts" here at the SuppVersity. The reason that's the figure of the week is that I have been thinking about ways to reorganize the archive, but am a bit lost on how to structure things in a better way using blogger. This beast simply isn't made for anything that goes beyond a weekly classic blogpost a la "last week I did this and that, read about..." *yawn*

What's yet even more enervating is that despite having the huge advantage of being easily posted and directly accessible for all of you, the tons of short news items I post on a daily basis on the SuppVersity Facebook Wall simply disappear into the 'Facebook nirvana'. I currently cannot spend any time on those technical / organizational matters, but in the course of 2013 things are going to change.

In the mean time, follow the SuppVersity on Facebook and read the news, right when I post them + use google to find articles you are looking for. You will be laughing, but that's the way I dig through those 920 posts, as well ;-) Simply type whatever you look for and add a "+site:suppversity.blogspot.com" to it.

Chinese fungi are laden with cancer-protective molecules and 5a-reductase (DHT) inhibitors

In view of a recent paper from the Universitat de Valencia (Rios. 2012) it appears that it would actually be hard not to decrease your risk of developing cancer if you include extracts from Ganoderma lucidum and other related fungi, such as Poria cocos, Laetiporus sulphureus, Inonotus obliquus, Antrodia camphorata, Daedalea dickinsii, and Elfvingia applanata in your supplement regimen. With a total of 81 compounds from Ganoderma lucidum and other species from this genus, as well as 96 compounds isolated from other fungi, principally Poria cocos. It appears that these creatures (fungi are no plants, neither are they animals, but still sort of living beings) could hold the key to hundreds o natural anti-cancer agents.

Ganoderma lucidum better known as Rheishi mushroom may have cancer protective effects, but does not taste so bitter that no sane human being would eat it for a reason (photo by Eric Steinert)
I guess, I don't have to tell you that Chinese Medicine, of course, knew about the powerful anti-inflammatory and anti-proliferative effects of the lanostanes in these fungi, all along. Intuitively and probably by trial and error, the Chinese have found the tetracyclic triterpenoids that are derived from lanosterols in these fungi to be effective in the treatment of various diseases including different types of cancer. As of late the mostly anecdotal effects are backed by more and more research. A preliminary study by Sliva et al. (Sliva. 2002), for example, found that a hot water extract of both spores and the dried fruiting body of G. lucidum inhibited the progression of cancerous growth by reducing the expression of constitutively active growth and inflammation promoting transcription factors AP-1 and NF-κB: 
"The extracts also inhibited the secretion of uPA, thereby suppressing the migration of breast cancer MDA-MB-231 and prostate PC-3 cells. [...] High levels of both uPA and uPAR are associated with advanced tumors and decreased survival time in different malignant human cancers." (Rios. 2012)
These benefits do however come with a downside. At least in vitro, some of the fungi, particularly G. lucidum, obviously exert their effects via anti-androgenic pathways (Liu. 2007). A compound in Reishi that goes by the name ganoderol B, for example, does not just have inhibitory activity against 5α-reductase, but can also bind to the androgen receptor directly (if you will you could say it acts like an anti-anabolic SARM). Now, this was good news in a study that has been conducted by Liu et al., because it inhibited androgen-induced cell growth in an LNCaP cell line while suppressing testosterone-induced regrowth of the ventral prostate in rats. If those effects are however non-selective, you are about to run into problems once the molecules bind to receptors outside the prostate -- epression for example, if they block the androgen effects in the brain, etc.
That reminds me: What did Carl say on Thursday's installment of the SuppVersity Science Round Up? "The good thing about supplements is that they work, the bad thing about them is that they work!" I guess you can basically say the same about Reishi. Good that you as a SuppVersity reader always know about both, the good and the bad sides of supplements!

More short news

With me posting stuff on the fly on facebook, I am actally 'wasting' many of the very short news items, but nevertheless, here are a couple of relatively short news to round things up.
  • If you missed Monday's new on the quasi non-existent thermogenic effects of ephedrine, this would be a good time to read that post.
    Stress-induced browning of the fat? Chronic overexpression of noradrenaline (re-)generates wasted brown fat! In a way this is a follow up on the ephedrine post "Fat Burners Don't Work" as well as an addendum to a news on the role of GABA and brown fat in obesity, I just posted on facebook. According to an allegedly old study in the International Jornal of Obesity (Lee. 1986),  the chronic overexpression of noradrenaline as it is observed in humans with a certain form of adrenal tumor known as phaeochromocytoma can actually reactivate the intra-abdominal fat of human adults, including the omental fat, which is brown adipose tissue in infancy.

    Lee et al. see this as one of the main contributing factors to the weight loss which is typically seen with phaeochromocytoma. Sounds, logical, since the same stimulus that rejuvenates the Brown fat will also have it burn energy continuously - the overexpression of noradrenaline.

    Symptoms of overtly high noradrenaline levels include abdominal pain, chest pain, irritability, nervousness, pallor, palpitations, rapid heart rate, severe headache, sweating, hand tremor, high blood pressure, sleeping difficulties, and also weight loss.
    Even patients with Cushing's syndrome (hypercortisolemia) there is an increase in brown fat compared to healthy individuals. That the latter is not as profound is probably due to the ameliorative effect of cortisol on nor-adrenaline. After all, cortisol comes into play, when the stress becomes chronic and the acute nor-adrenaline response to stress, when it was prlonged any further would actually pose a direct threat to your health (just as phaeochromocytoma does, by the way; see red box on the right)
  • Repeated moderate stress exposure increases DHEA production and normalizes corticosteriod levels in old apes (Goncharova. 2012). Yep, you are reading right we are not just talking about no rodent studies (although macacs are not exactly very human either ;-), but also about the role of repeated moderate stress in the normalization of aged induced abnormalities in the expression of adrenal hormones.
    Figure 2: Cortisol/DHEA ratio before and after 2h/day of immobilization stress.
    "In old monkeys the basal DHEAS levels were lower, while the [cortisol]/DHEAS ratio was higher than in young animals. Repeated immobilizations inhibited [cortisol] elevation on day 3, caused no changes in DHEAS reaction, led to increase of basal DHEAS levels and to a reduction of [cortisol]/DHEAS ratio on days 2, 3, 4, 10, 11." (Goncharova. 2012)
    In figure 2 you can see how profound the differences between acute, subchronic (3-day) and chronic responses actually are and that after 10 days of daily stress exposure in the form of daily 2-h immobilization stress actually are. Since I assume you don't want to be bound or enchained (well, maybe you want?), I suppose a viable alternative could be a shorter not too intense workout, although the acute responses to the latter vary with age as well (cf. Lennartsson. 2007).
  • Monitor your DHEA levels closely, if you are concerned about joint degeneration According to a study that's about to be published in the next issue of the Journal of Steroid Biochemistry and Molecular Biology, DHEA, or the estradiol your body generates from it via local aromatization, exerts major protective effects against osteoarthritis (Li. 2012).

    An additional note of caution with respect to the abuse of aromatase inhibitors, natural or not. Since they have the potential to reduce the expression of estrogen at the neuronal level in the brain they can precipitate  Alzheimer's dementia. While estrogen appears to decrease the MMP-3 & 13 expression in the cartilage reasearch by Merlo et al. suggests that it will increase others, namely namely MMP-2 and MMP-9  in the brain and thus facilitate the clearance of the ameloid beta plague that's rendering the brains of AD patients more and more dysfunctional (Merlo. 2012). You see, it's no chance that pre-menopausal women are protected from Alzheimer's yet more susceptible to multiple sclerosis (MS). After all, high MMPs 7 & 9 have only been observed in kids with MS, as well (Unsal. 2012).
    In their experiments on a rabbit model of osteoarthritis the scientists from the Zheejiang University in China tried to nail down the beneficial effects of DHEA on chrondocites and cartilage to estrogen by co-administering DHEA with the aromatase inhibitor letrozole, and/or the estrogen receptor inhibitor fulvestrant and observed that the
    "[e]xpression of MMP-3 and MMP-13 increased in both DHEA-treated chondrocytes and cartilage in the presence of letrozole and/or fulvestrant, while the expression of TIMP-1 and collagen type II (Col-II) decreased." (Li. 2012)
    With the former metalloproteinases (MMPs) being proteolytic enzymes, which break down cartilage and the latter, i.e. the tissue inhibitors of metalloproteinases (TIMPs), acting as their antagonists, it appears clear why both patients on testosterone replacement therapy who use too high of a dose of aromatase inhibitors and athletes who abuse respective products on cycle or during PCT often suffer from severe cartilage degeneration - I mean, combine the endogenous cartilage destruction due to high MMPs and low TIMP levels with the wear and tear of weight lifting... what good could come out of that?

    Note: A very similar effect has been reported for bisphenol A by Wang et al. in 2010, already (Wang. 2010). No wonder, after all BPA decreases the local expression of aromatization in joints and cartilage so that less estrogen will be floating around to keep the MMP levels in check and TIMP up (Watanabe. 2012).
  • Alpha tocopherol to prevent lymphoma Regular vitamin E, i.e. the alpha-version of the tocopherols is no longer the star at the supplement sky it has once been hailed to be. A recent study by Renu Sharma Manjula Vinaya that's been published ahead of print in the journal Molecular Biology Reports shows however that this does not mean that it's outdated and useless (ask Ray Peat about it ;-).

    Figure 3: Lifespan (top) and ascite volume (=water accumulation in the abdominal area) of lymphoma carrying mice treated with what would be in human terms ~325, 650 and 975 IU/day of an alpha tocopherol only supplement  (Sharma. 2012)
    In order to test the hypothesis that the ROS scavenging abilities of vitamin E should help with cancer prevention (as a student of the SuppVersity you know that respective data from epidemiological studies are equivocal, some suggesting the exact opposite; read more), the researchers initially induced the growth of lymphomas in 10-15 week old male mice and subsequently treated them with either 1.5 mg (50 mg/kg bw), 3 mg (100 mg/kg bw) or 4.5 mg (150 mg/kg bw) of alpha-tocopherol for 14 days.

    As the data in figure 1 goes to show you, the treatment increased the lifespan of the rodents by 25% and reduced the ascite fluid volme (see image in figure 1) by ~46%. This was accompanied by reductions in protein carbonylation and increases in the "master anti-oxidant" GSH, as well as several other markers showing that vitamin E exerted profound anti-inflammatory effects in this rodent model of lymphoma.

    At least in my humble opinion that does not change the fact that your best sources of vitamin E are natural and that's smart to stay away from alpha-tocopherol only supplements and prefer a whole spectrum tocopherol + tocotrienol supplement. Remember: More is not better, when the one thing that counts are the ratios (read more about vitamin E)!
That's it for this week's installment of On Short Notice. As mentioned in the introduction, there are more and even shorter news on the SuppVersity Facebook Wall, which usually gets updated 3+ times per day with I would guess 9-12 items total - depending on whether it's a slow news day or not and the time I have to skim studies and popular science mags and repost summaries and links of and to the latter. Let's see what did we have today, already? Ah, yeah: "Review concludes: Just being patented makes Kinesio® no better than conventional taping" (more), "Interesting stupid science finds that GABA directly mediates energy expenditure." (more), or maybe you are interested in "If rapamycin blocks seizures in model of epilepsy. Is mTOR to blame for both?" (more)?

References:
  • Goncharova ND, Vengerin AA, Chigarova OA. Repeated Moderate Stress Stimulates the Production of Dehydroepiandrosterone Sulfate (DHEAS) and Reduces Corticosteroid Imbalance in Old Macaca Mulatta.  Bulletin of Experimental Biology and Medicine Volume 153, Number 5 (2012), 750-753. 
  • Lean ME, James WP, Jennings G, Trayhurn P. Brown adipose tissue in patients with phaeochromocytoma. Int J Obes. 1986;10(3):219-27. 
  • Lennartsson AK, Kushnir MM, Bergquist J, Jonsdottir IH. DHEA and DHEA-S response to acute psychosocial stress in healthy men and women. Biol Psychol. 2012 May;90(2):143-9.  
  • Li WJ, Tang LP, Xiong Y, Zhou XD, Wu LD. The chondroprotective effects of dehydroepiandrosterone probably exerted by its conversion to estradiol. J Steroid Biochem Mol Biol. 2012 Oct 18. 
  • Liu J, Shimizu K, Konishi F, Kumamoto S, Kondo R. The anti-androgen effect of ganoderol B isolated from the fruiting body of Ganoderma lucidum. Bioorg Med Chem. 2007 Jul 15;15(14):4966-72. 
  • Merlo S, Sortino MA. Estrogen activates matrix metalloproteinases-2 and -9 to increase beta amyloid degradation. Mol Cell Neurosci. 2012 Apr;49(4):423-9.
  • Ríos JL, Andújar I, Recio MC, Giner RM. Lanostanoids from Fungi: A Group of Potential Anticancer Compounds. J Nat Prod. 2012 Oct 23.
  • Sharma R, Vinayak M. α-Tocopherol prevents lymphoma by improving antioxidant defence system of mice. Mol Biol Rep. 2012 Oct 14.
  • Sliva, D.; Labarrere, C.; Slivova, V.; Sedlak, M.; Lloyd, F. P., Jr.; Ho, N. W. Biochem. Biophys. Res. Commun. 2002, 298, 603– 612.
  • Unsal Y, Kıvılcım G, Ayşegül A, Arzu A, Esra G, Ercan D, Ayşe S. Matrix metalloproteinase-7 and matrix metalloproteinase-9 in pediatric multiple sclerosis. Pediatr Neurol. 2012 Sep;47(3):171-6.
  • Wang KC, Lin YF, Qin CH, Chen TL, Chen CH. Bisphenol-A interferes with estradiol-mediated protection in osteoarthritic chondrocytes. Toxicol Lett. 2010 Oct 5;198(2):127-33. 
  • Watanabe M, Ohno S, Nakajin S. Effects of bisphenol A on the expression of cytochrome P450 aromatase (CYP19) in human fetal osteoblastic and granulosa cell-like cell lines. Toxicol Lett. 2012 Apr 5;210(1):95-9.