2g Vitamin C Ameliorate Low Testosterone Levels and Sexual Dysfunction in Diabetic Rats. Usefulness in Normoglycemic Individuals Still Questionable.

Illustration 1: In view of the increase in renal
vitamin C clearance with higher plasma levels
(Friedmann. 1940), it may be sensible to use a
time-released vitamin C formula, or, even
better, eat a serving of veggies or fruits that
are high in vitamin C multiple times a day

Yes, I know, supplemental vitamin C does not ward off the common cold... the same applies for taking super high doses of vitamin C as antioxidant buffers before or around workouts. In fact, studies have shown that the antioxidant overkill of a combination of vitamin C and other powerful antioxidants could negate the beneficial effects exercise has on human blood glucose management. Now, a group of Brazilian scientists has published a rodent study that seems to suggest that in the absence of exercise the addition of 2g (human equivalent for 80kg male) of vitamin C to your diet could partially restore sexually function and increase testosterone levels in diabetic patients (Fernandez. 2011).

In their study, the Fernandez et al. had fed 10 out of 20 hyperglycemic rats vitamin C enriched chow (+150mg) and found that the addition of the water-soluble vitamin had beneficial effects on oxidative strees biomarkers in the erythrocytes, which have proven to be a valuable indicator of stress levels for the whole body (Naziroğlu. 2001; Garg. 2000)] (cf. figure 1),

Figure 1: Stress markers TBARS, SOD, GSHt and GSH/Px in hyperglycemic rats after 30 days on normal (placebo) and vitamin C enriched chow; data expressed relative to normoglycemic controls (data adapted from Fernandez. 2011)

as well as reproductive organ weights, sperm parameters, plasma hormone levels (FSH, LH and testosterone), testicular and epididymal histo-morphometry and histopathology.of the hyperglycemic rats (cf. figure 2).

Figure 2: Organ weights (*visceral fat / 100g), reproductive hormones and sperm number and quality in hyperglycemic rats after 30 days on normal (placebo) or vitamin C enriched chow; values expressed relative to normoglycemic control (data adapted from Fernandez. 2011)

Vitamin C supplemented or not, compared to the normoglycemic control,  the diabetic rats must still be regarded as partially impotent and overall sickly, which is an observation the scientists omit, when they conclude

[...] the present study showed that vitamin C supplementation minimized some alterations in the male reproductive system caused by hyperglycemia such as reduction of testosterone and LH levels and impairment in sperm morphology. [italicization by Dr. Andro]

After all, what's the worth of a "minimizing" the negative effect on testosterone levels to  -71%? This may be 10% less damage than without vitamin C, but wouldn't it be much better not to get yourself into such a misery in the first place?

Note! Not everything that is good for sick people makes a viable addition to the supplementation regimen of a healthy or even athletic person. Even Fernandes and her co-workers emphasize that "is possible that the beneficial effects of vitamin C supplementation are only relevant to those individuals with low levels of vitamin C and high levels of oxidative stress that occur in hyperglycemic condition."

Well, regular exercise and the avoidance of high fructose corn syrup and the other sweet suspects you poise yourself with on a daily basis would be the way to go - and you know that!

Gingko Biloba, Your Dopaminergic Brain Viagra. Plant Extract Stimulates Sexual Arousal via the Paraventricular Nucleus and the Mesolimbic System.

Image 1: Gingko biloba
trees are one of a kind, with
no close living relatives
(image Schwabe Pharm.)

I bet you got one of those Viagra spam mails, today, as well, didn't you? Well, although I assume you would not need the small blue pills, anyway, you may be interest to read that researchers from the People's Republic of China may have found a viable Viagra alternative in a longstanding (pun intended ;-) ingredient of Traditional Chinese (and meanwhile also Western) Medicine: Gingko biloba.

In order to elucidate the underlying mechanisms of previously (Yeh. 2010) observed beneficial effects of Ginkgo biloba extract on noncontact erections in male rats, Yeh et al. (Yeh. 2011) recorded both copulation, as well as non-contact erections in a group of 20 male Long-Evans (telling name, isn't it?) rats, which had been randomly assigned to a treatment (50mg/kg body weight Gingko biloba extract [EGb 761 from Schwabe Pharmaceuticals], human equivalent 8mg/kg ~ 640mg for an 80kg man) or a control group. 14 days after initiation of treatment, there was "a significant increase in the number of NCEs [non contact erections]" in the 10 rats of the treatment group. Furthermore,

[...] the expression of catecholaminergic neurons in the PVN [paraventricular nucleus] and the VTA [ventral tegmental area] was seen [to be significantly increased ...] and tissue levels of dopamine and 3,4-dihydroxyphenylacetic acid in the NAc [nucleus accubens] were also markedly increased in the EGb 761-treated animals. However, the norepinephrine tissue levels in the PVN and the NAc in the EGb 761-treated group were not significantly different from those in the controls.

In other words, the increased number of catecholaminergic neurons did not, as one might have expected, increase the total amount of the stress-related neurotransmitter /hormone norepinephrine. In agreement with previous work by Mas et al., 1990; Pfaus et al., 1990; Pleim et al., 1990;Wenkstern et al., 1993; Tsai et al., 2006, it's dopaminergenic effects in the nuccleus accubens (dopamine levels in the increased by 66%), on the other hand, had profound effects on their sexual behavior (cf. figure 1).

Figure 1: Effect of Gingko biloba extract @ 50mg/kg on non-contact erection frequency in male Long-Evans rats before and after 14 day treatment (data adapted from Yeh. 2011)

In view of the effect, that the scientist do not want to "exclude that EGb 761 treatment may also influence dopaminergic activity in other brain areas", these results may be of interest even to those among you, who do not have any trouble "getting it up".

Note: The mechanism by which Gingko biloba increases sexual desire is different from the one of PDE-5 inhibitors such as avanafil, lodenafil, mirodenafil, sildenafil citrate, tadalafil and all the other "-afils". While the systemic effect on nitric oxide induced vasolidation of Viagra and Co. will help with erection quality and quantity, Gingko biloba probably won't help if blood flow restriction in your most valuable part is an issue. The different mechanisms of action, on the other hand, would suggest the two would make an interesting stack. And in fact back in 2010 Kim et al. found that "GBE [Gingko biloba extract] could increase the relaxant potency of mirodenafil even at a minimally effective dose" (Kim. 2010).

With dopamine playing an important role in behavior and cognition, voluntary movement, motivation, punishment and reward, inhibition of prolactin production (juicers did you read that?), sleep, mood, attention, working memory, and learning, the implications of this finding reach beyond sexual function alone. Even in the etiology of the dubious central fatique syndrome, every second visitor of one of the major internet health bulletin boards claims to experience, these days, may involve dopamine or rather a lack thereof (Caldizán Uzón. 2008). That being said, the group of patients who benefit from one of the readily available over-the-counter Gingko biloba supplements may soon expand from best agers, who are concerned about cognitive decline to (pre-)andropausal men who want to regain their interest in the fairer sex and, eventually, everyone who feels he/she would benefit from some additional dopaminergic drive.

Andropause? Low Testosterone? At Risk of Developing Diabetes? Get a Free Hormonal Panel and Access Your Personal Health Risks With an Old-Fashioned Measuring Tape.

Image 1: Not as realiable as bloodwork,
but a valid first indicator of testosterone
levels and metabolic health in general
(image from Millionlineincome)

I have been writing about getting hormones tested before. And if you listened to Thursday's episode of Super Human Radio and tuned in even before I was on, you will have heard Dr. Crisler from "All Things Male" talk about the paramount importance of optimal testosterone and free testosterone levels on physiological and pyschological health of the purportedly "stronger" sex (yeah, I am talking about us, guys ;-) If that got you interested or you suspect, for whatever reason, to have low testosterone levels, but are unwilling or unable to spend money on a blood test, you may well be interested in the results of a study that was published in the May issue of the Asian Journal of Andrology (Alan. 2011).

Alan et al. who investigated the relationship of age, adiposity and testosterone levels in 207 otherwise healthy aging men (>= 54 year) with symptoms of hypoandrogenism found a significant correlation of both total and free testosterone levels and the waist-to-height (WHt) ratio of their subjects:

[...] WHt ratio was more strongly correlated with TT and cFT than either WC [waist circumference] or BMI. Furthermore, in models of TT and cFT, the addition of Ht to WC resulted in an increase in the magnitude of the regression coefficients for both WC (inverse correlate) and Ht (positive correlate), with the contributions of both WC and Ht both being significant (P<0.05 for all).

Table 1: Waist-to-height ratio corresponding
to increased risk of high blood pressure,
elevated blood glucose and high triglyceride
levels (data adapted from Leitzmann. 2010)

Or in other words, if your tall and lean chances are your erectile dysfunction or whatever possibly androgen-related problem is plaguing you, is not a result of low testosterone levels. While this does not exclude the possibility that overtly high estrogen levels or low 5a-reductase activity and consequently low DHT levels (I have written about the importance of DHT in the context of "all things male" before) are at the bottom of your problems, you will at least know that checking testosterone alone probably won't provide the answer to your question.

On the other hand, these results exemplify the viscous circle of how low, or as many family physicians like to refer to them, "age appropriate", androgen levels, predispose to (predominantly visceral) adiposity, which - apart from its direct detrimental effects on metabolic health (cf. table 1) - in turn increases aromatization of testosterone to estrogen and thus further reduce the availability of the primary male sex steroid. While it appears that this is another instance of the "chicken and the egg, who was first?"-question, I would argue that chances are that the "age appropriate" decline in androgen levels goes hand in hand with increasing obesity and should thus also be addressed by a multi-faceted approach constituting of professionally* supervised hormone replacement therapy and appropriate life-style changes, in other words, the incorporation of regular exercise and healthy eating habits into your daily routine.

* the attribute "professional" obviously excludes your average family Dr. who considers your testosterone level "age appropriate" and refuses to measure estrogen, DHT, DHEA and all the other endocrine parameters without which you will never get the full picture

Now Its Official: Propecia Drug Finasteride Kills Male Libido Permanently

Image 1: Chemical structure of finasteride

Other than the FDA some European medicine and health care agencies, such as the Swedish Medical Products Agency and the Medicines and Healthcare Products Regulatory Agency of the United Kingdom already had the guts to declare in their patient informations that "persistence of erectile dysfunction after discontinuation of treatment with Propecia has been reported in post-marketing use." While this was obviously no reason for the all-mighty FDA to correct or re-evaluate their own documents, two it did intrigue Michael S. Irwig and Swapna Kolukula, two US scientists from Washington and Baltimore, respectively.

In their study (Irwig. 2011), the scientists conducted standardized interviews with 71 otherwise healthy men (age: 21–46y), who experienced permanent (>3 months) sexual side effects after temporary use of Finasteride. Their reports are staggering:

94% developed low libido, 92% developed erectile dysfunction, 92% developed decreased arousal, and 69% developed problems with orgasm. The mean number of sexual episodes per month dropped and the total sexual dysfunction score increased for before and after finasteride use according to the Arizona Sexual Experience Scale (P < 0.0001 for both).

These sexual side effects occurred after a "mean duration of finasteride use [of] 28 months" and they were persistent up to the interview date. For the study population this meant that they had already been suffering 40 months, on average, when the interviews took place; and chances are that many of them will suffer the consequences of an insufficient (or should I say incompetent or corrupted?) drug approval process and consequent indoctrination of medical practitioners for the rest of their lives.

Note: After receiving some critical feedback via facebook, I feel that it is necessary to point out that the result of the study may not be misinterpreted as "Every Finasteride user will experience persistent decreases in libido, erectile disfunction etc.", but as "In those percentage of Finasteride users, where such side effects occur, they can potentially be permanent." So the news is neither that Finasteride will cause these effects in each and every user, nor that it may cause such side effects (that is in fact mentioned in the package insert, I suppose), but that IF side effects occur, it is possible that they are persistent.

Vitamin A Regrows Liver Tissue. Polydextrose Makes Dieting a Breeze. Exercise Blunts Negative Effects of High Fructose Diet. Diabetes Precipitates Female Sexual Dysfunction.

I did miss my own 1000-posts jubilee!

This week it's pretty easy to find the SuppVersity figure of the week. It's 1011 and that's the number of individual posts this "blog" currently holds. Actually, the very moment I hit the "publish" button on this one, it's going to be 1012 (see image on the right). I guess, I should have 'celebrated' that twelve posts before, but you know how I am, it's about the quality, not the quantity and though I am aware that the latter is unquestionably fluctuating, I would hope that each of you has found one or two 'pearls' - I mean, if you didn't why are you coming back regularly, then?

Apropos regularly, it's Saturday and thus about time for a couple of "On Short Notice" items. So let's not waste any time flattering and get to the science news business:

Vitamin A essential for liver regeneration. Plus: β-carotene and cancer even in non-smokers

So much for the vitamin A vs. D antagonism - in fact, one can't go without the other: Vitamin A & D synergize against liver cancer and increase survival rates by more then 75% (read more)

(Blaner 2013) -- Other than SuppVersity readers, the average slef-proclaimed health-conscious citizen probably thinks of (false) horror stories about vitamin A laden polar bear livers killing a handful of ravenous arctic explorers. The fact that the active form of vitamin A is actually one of the most important hormone-like substances in your body that's essential for the maturation process of stem cells, on the other had, got lost at least since vitamin D the supposed vitamin A antagonist became all the rage in the past decade. Scientists from the Coumbia University in New York and the Chernivtsi National University in Chernivtsi, Ukraine, are now going to publish a paper that should remind everyone (including the science community) that the contemporary black and white painting on D & A may well impair the progress we make in our understanding of our own physiology.

Missing half your liver? Not a problem if you got enough "liver building" vitamin A ;-)

In a mouse model which has been genetically modified so that the rodents weren't able to store adequate levels of retinoids  (yeah, there is a whole family of "vitamins A") in the liver, showed a delayed and incomplete regenerative response to partial hepatectomy (cutting away parts of the liver; PHE). As the scientists point out,

"[t]he requirement for proper retinoic acid signaling to allow for normal liver regeneration is underscored by studies of hepatocyte-specific RXRα-null mice [mice lacking the retinoid receptor]. When RXRα is ablated there is reduced hepatocyte lifespan, which is accompanied by premature hepatocyte death and the appearance of necrotic areas. RXRα ablation also results in delayed hepatocyte proliferation following PHE." (Blaner 2013)

At first sight this observation goes again the often cited liver-toxicity of vitamin A. In view of nature's favorite dose-response curve, which is bell-shaped and indicates that bad things (often similar or even identical ones) happen in both deficiency and toxicity states, it's only logical, though. Plus, similar effects have been observed for wound-healing decades ago (Gerber. 1982) and Ehrlich and Hunt report in a 1968 paper in the Annals of Surgery that the administration of vitamin A blunts the negative effects on cortisol on wound healing and appears to be necessary for optimal tissue regeneration (Ehrlich. 1968).

So, another good reason to pop vitamin A supplements?

Supplementation with very high doses of isolated beta-carotene could in fact induce a state of "vitamin A resistance" in response to the formation of a metabolite that blocks the RXR receptor just like a SERM like clomiphene citrate block the estrogen receptor (read more).

For a healthy person living on a paleo-esque diet supplements should not be necessary. The amount of vitamin A and its pre-cursor beta-carotene you get from a whole-foods diet is usually adequate, even if you don't consume liver or organ meat on a regular basis. The use of what you will generally get, when you go to a healthfood store and buy a "vitamin A" supplement, i.e. a high dose beta carotene, only, product is probably counter-indicated not just for smokers, where it appears to increase the risk of lung cancer development, but also in normal healthy individuals who usually get plenty of beta-carotene from the myriad of fortified foods your local supermarket has to offer - after all, one of the most recent meta-analyses showed that 20-30mg/day increase everyone's risk of lung cancer development by 16% and that of stomach cancer by 34% (Druesne-Pecollo. 2010).

Polydextrose has non-noticeable, but significant satiety effects

(Astbury. 2013) -- I know the headline sounds confusing, but basically that's the long and short of the results, Astbury, Taylor and MacDonald present in their most recent isse in the British Journal of Nutrition. The scientists fed 12 male and 9 female healthy university students (mean age 23.2y; BMI 22.3kg/m²) who had consumed identical breakfasts at 8:00am with isocaloric (210kcal) "preload" mid-morning snacks at 10:45am and 90min before they had a pasta-based test meal, of which they were supposed to eat as much as it would take to feel comfortably full.

Figure 1: Food intake (in kcal) after mid-morning snack with different amounts of polydextrose (left); caloric intake on the subsequent meals of the day (right; Astbury. 2013)

As the data in figure 1 indicates, the consumption of the liquid preload which contained either 0, 6.3, 12 or 21g of the sweet tasting polysaccharide that reaches the colon largely undigested, where 50% of the polydextrose molecules will be fermented to yield CO2 and volatile SCFA such as propionate and butyrate and the rest will be excreted intact in the feces lead to dose-dependent reductions in the amount of food that was consumed in the subsequent meal.

50% energy availability, a source of SCFA, tasty & easy to process - perfect diet 'food'?

With only 50% energy availability and 50% being fermented to short chain fatty acids (SFCA),  the 89% dextrose, 10% sorbitol & 1% percent citric acid molecule, polydextrose could actually be a better choice for dieters than WMHDP (learn more about the SCFA based fat burning effects of resistant starches and how to make fat burning pancakes)

Interestingly, the reduced energy intake was not brought about by a consciously noticeable reduction in either fullness, hunger or desire to eat in response to the test meal (the scientists assessed that by questionnaires). And despite the fact that the effect was only transient, it's actually good and important news that the men and women did not accommodate for the 12-23% (male participants) and 6-18% (female participants) reduction in energy intake on the subsequent meal.

If that worked with every meal and you could achieve a ~20% reduction in energy intake, this alone should help you shed some weight pretty effortlessly. And as if that was not enough, already the polydextrose drinks was even more palatable than the sugary original; with the highest polydextrose content being perceived as most "creamy" - bon appetit ;-)

Even shorter news - "On real short notice", so to say  ;-)

I am well aware that what began as short news has as of late turned into a bunch of regular news - well, almost. So I decided to try and cut the last two items in today's installment short, in order to have them fit into what you would actually expect from a "on short notice" ;-)

• Exercise nullifies bad effects of high fructose diet (Moraes-Silva. 2013) -- A paper by scientists from the University of Sao Paulo puts the "lack of exercise / insuficient activity" hypothesis of obesity back on the radar. Even with an otherwise highly detrimental liquid fructose overload of 100g/l in their drinking water, the rodents in the study Moraes-Silva et al. conducted, did have normal (within statistical limits) glucose tolerance, blood pressure and heart disease risk as the rodents in the sedentary and the exercised control groups.

  

  Figure 2: Regular exercise maintains insulin sensitivity, cardiovascular disease risk and blood pressure even in the presence of pathologically high liquid fructose ingestion (Moraes-Silva. 2013)

  The regular treadmill running also blunted the autonomic dysfunction that was characterized by "an approximate 50% decrease in baroreflex sensitivity and 24% in HR variability", as well as increases in sympathovagal balance (140%) and renal sympathetic nerve activity (45%). Now you tell me "it's all about diet", only. Let alone: "Exercise just makes you hungry!"

• Diabetes and female sexual dysfunction correlate (Pontiroli. 2013) -- We already know that diabetes is a, if not the #1 risk factor for male sexual dysfunction, these days. Now a recent meta-analysis that's going to be published in one of the future issues of The Journal of Sexual Medicine found a 150% increase in sexual dysfunction in type II diabetes. Whether or not this was related to the higher depression rates in diabetic women cannot be said. What is certain, though, is that the BMI was a positive predictor of the effect size. In other words, the negative impact on sexual function increased with the degree of adiposity.
  
  Additional read for those women who feel it's their husband's performance that's to blame for their anorgasmia: "Pedalium murex Linn. fruits more effective than sildenafil in the long run and increases testosterone by 125%" (read more)
   

Now that's it for today, but I am now going out on a limb and promise another serving of short news with a focus on exercise early next week - something like the previous "Health & Exercise"- or the "Get Lean & Stay Lean" quickies and for once I can even tell you about one news that's definitely going to be in there - something about working out with and without breakfast.

---

The obligatory reminder: In the mean time I'd suggest you devour the latest SuppVersity Facebook News @ www.facebook.com/SuppVersity. As usual they will receive a couple of updates way before the next official SuppVersity post is going to see the light of the day. Let's see, some of the most recent news are even remotely related to the On Short Notice items of today:

• Penis pumps - Scientists believe they are going to make a revival as a means of penile rehabilitation after surgery for prostate cancer (read more)
• Stress renders cancer immortal - What has just been observed in a rodent model of prostate cancer could have important implications for other cancers, as well (read more)
• PDE5 inhibitor for him, PDE-4 inhibitor for her? Study suggests: PDE-4 inhibitors could improve female sexual function (read more)
• Goose liver for the liver - When it's high in selenium goose liver could protect your liver from the assault of excessive alcohol consumption (read more)

As promised, there will be more. So in case you have not done so already,  you best like the SuppVersity right now so that the latest news will always appear in your news-feed.... ah, and about all that geeky science reading, don't forget that there is more to life than dieting and working out ;-)

References:

• Astbury NM, Taylor MA, Macdonald IA. Polydextrose results in a dose-dependent reduction in ad libitum energy intake at a subsequent test meal. Br J Nutr. 2013 Jan 23:1-9.
• Druesne-Pecollo N, Latino-Martel P, Norat T, Barrandon E, Bertrais S, Galan P, Hercberg S. Beta-carotene supplementation and cancer risk: a systematic review and metaanalysis of randomized controlled trials. Int J Cancer. 2010 Jul 1;127(1):172-84.
• Ehrlich HP, Hunt TK. Effects of cortisone and vitamin A on wound healing. Ann Surg. 1968 Mar;167(3):324-8.
• Gerber LE, Erdman JW Jr. Effect of dietary retinyl acetate, beta-carotene and retinoic acid on wound healing in rats. J Nutr. 1982 Aug;112(8):1555-64.
• Moraes-Silva IC, Mostarda CT, Moreira ED, Silva KA, Dos Santos F, De Angelis K, Farah VD, Irigoyen MC. Preventive role of exercise training in autonomic, hemodynamic and metabolic parameters in rats under high risk of metabolic syndrome development. J Appl Physiol. 2013 Jan 17.
• Pontiroli AE, Cortelazzi D, and Morabito A. Female Sexual Dysfunction and Diabetes: A Systematic Review and Meta-Analysis. J Sex Med. 2013 [e-pub ahead of print]