Natural Sildenafil & Testosterone Alternatives: Pedalium Murex & Paederia Foetida +150% Testosterone and +200% Erectile Function. Plus: Icariin, Aromatase & Stronger Bones. Probiotics, Phytosterols & Thyroid Activity.

If the Aliens have seen these Bugarash apocalypse pilgrims, they have probably turned tail and fled ;-)

I guess the SuppVersity figure of the week was a date "12/21/2012", I mean this is a once in a life-time event! Or do you really believe there will be another chance for mankind to be snatched from the jaws of extinction?

Ok, enough of the sarcasm, the world is still there and the SuppVersity is still operating, so let's get to the not so short On Short Notice items for today.

If there had been more room in the headline I would probably have labeled it "Endocrine Special" and I guess once you have gone through the posts, you will agree that this would certainly have made sense.

• Traditional treatment of osteopenia with Epimedium brevicornum works, 'cause it's a potent aromatase promoter (Yang. 2012) -- When a group of researchers from the Chengdu Institute of Biology, Chinese Academy of Sciences and the School of Chinese Pharmacy, Chengdu University of Traditional Chinese Medicine in Chengdu, China, set out to investigate the mechanism behind the anti-osteoporotic effects of the dried leave extract from Epimedium brevicornum, they already suspected that it would probably be related to some sort of endocrine modulation.
  
  

  

  Figure 1: In vitro effect of Forskolin and Icariin on aromatase expression in KGN cells (Yang. 2012)

  With estrogen deficiency being the major cause of osteoporosis, a disease which does by the way affect over 200 million people worldwide (Riggs. 1998), being their the most likely mechanism behind the bone building and bone mineral density (BMD) protective effects, it was obvious to study, whether there was some sort of interaction between the extract and the data in figure 1 shows that Yang et al. were right to do so (note: the cell line used in the study was a KGN granulosa cell that's closely associated with the developing female oocyte, so effects could vary from one tissue to the other)
  
  Now all that certainly sounds as if this was bad stuff no sane male human being should be taking. Luckily, for many of you, my fellow men, who may have been exposed to Epimidium / Icariin from various supplements, this is not the case. Why? Simply because estrogen is not the enemy and Epimidium has not only been found to have anti-aging effects (whole extracts; Yan. 2009), it also prevents neurotoxicity from beta-amyloid plague the key feature of Alzheimer's and similar diseases (Zeng. 2010; listen to Thursday's Science Round-Up for other amyloid beta inhibitors / protectant's) and the neurotoxic effects of excess corticosteroids (Liu. 2011). In addition, Epimidium pubescen flavenoids have been shown to reverse the negative effects even passive exposure to cigarette smoke may have on the bone mineral density of male rats (Gao. 2012) and Icariin the common denominator in all of the members of the Epimidium family exerts direct proliferative and thus pro-fertility effects on the sertoli cells in male rodents (Nan. 2012).
  
  

  

  Table 1: Analysis of Chinese Epimidium species (MDida. 2010)

  Ah, and last but not least the beneficial effect Horny Goat Weed (likewise one of the members of the Epimidium family) has on male libido are likely partly a result of the increased aromatase activity, as well. If it works for you, your estrogen levels are probably pretty low to begin with (this reasoning is based on the profound beneficial effects of estrogen on male libido in men expressing little to no aromatase enzyme; Carani. 1999).

• Pedalium murex Linn. fruits may not be as potent acute libido and erectile performance enhancers as sildenafil, but the effects accumulate and persist just as its unique testosterone boosting effects (Sharma. 2012) -- In case taking a potential proestrogenic compound like Horny Goat is nothing you feel would do anything good for your libido, you may want to use some Pedalium murex Linn. in traditional Indian medicinea herb that has been used in traditional Indian medicine for centuries to treat male sexual dysfunction and impotency.
  

  

  Figure 2: Effects of different doses of an ethanolic extract from Pedalium murex (P.m.) and Sildenafil citrate (5mgkg) on penile erection scores and post ejaculatory interval (time it takes to be able to have sex again) exrpessed relative to saline treated control (based on Sharma. 2012)

  As the data in figure 2 shows, its effects on erectile performance are slightly less pronounced than those of sildenafil citrate, but at an appropriate dosage and after some time, it will probably do its job sufficiently for most men with respective problems. What's really exiting though, is that the data in figure 3 clearly shows that it does so not by simple nitric oxide effects (P. murex at 10 mg/
  ml exhibited a relative nitric oxide release of 15.3 mM as compared to a nitric oxide release of 39.3472.7 mM with sildenafil citrate), but probably (also) by boosting testosterone levels. 
  
  

  

  Figure 3: Serum testosterone levels during and after Pedalium murex or Sildenafil citrate administration expressed relative to saline control (Sharma. 2012)

  Since the testosterone levels remained elevated for 14 days after the treatment was seized these observations make P. murex a potential candidate for the next best natty test booster.to be powered by advertisement lines like "up to 125% increase in testosterone that last for more than 2 weeks" even when you take some time off. I guess, the only serious downside here is the close relation of P. murex to the notoriously useless Tribulus, which does also contain furostanol glycosides. Luckily Magnle and Jolley found another potentially active ingredient in P. murex fruit. The compound goes by the name diosgenin and appears to be a direct precursor for the synthesis of sex hormones including testosterone (Mangle. 1998).
  
  Since I don't think you will have to wait very long until the first major players in the supplement business will jump on this bandwagon - you know that a single rodent study is enough to make fortune until people realize that this stuff does not work, at all - you will probably soon be able to test it on yourself. In case you intend to do that, you should certainly look for a standardized ethanolic extract with ~20%+ of diosgenin (that was the content of the extract Sharma et al. used) and a serving size of 16.2mg/kg per body weight, the HED of the 100mg/kg group (that would be 1,300mg /day of the extract for an 80kg adult).

• Paederia foetida Linn. (P. foetida) yet another Indian libido and testosterone boosting herb (Soni. 2012) -- If you like the appeal of exclusiveness a climbing plant found in the Central and Eastern Himalayas, at elevations of up to 5000 ft, you may prefer the an ethanol extract of Paederia foetida Linn. (P. foetida) leaves over the previously discussed Pedalium murex fruit extract.
  
  

  

  Figure 4: Penile erection index and testosterone levels of rats after 15 and 28 days on P. foetida, data expressed relative to saline control (Soni. 2012)

  According to a recent study from the same group of Indian scientists (yet a different lead author), the effects of P. foetida and P. murex are in fact virtually identical. While the general protocol was very similar (in this done on rat, not mice) the positive control was not Sildenafil citrate, as in the previously mentioned experiment, but an intramuscular injection of 0.5 mg/kg body weight of testosterone suspension in arachis oil twice a week. It's actually a pity the scientists didn't measure the actual testosterone levels in the animals in the testosterone group. I would be curious how the 2.5x increase in the high dose group (200mg/kg, human equivalent ~2,600mg/day) would compare. When it comes to the erection quality, it did at least easily top the results of injectable testosterone (see figure 4), which is yet allegedly not the best erection booster, anyway. And if we went by the data on body weight and the weight of the testes, seminal vesicles, prostate glands and epididymis, it even appears to be more anabolic than testosterone; after all the body weight gain in the PF groups were 15%. 23% and 34% higher than in the control group and comparable if not higher to those that were induced by testosterone (+29%).
  
  And for all the supplement producers and fans of stacks it may be important to know that the leaves of P. foetida, which is also used as carminative, antiinflammatory, astringent, spasmolytic, antidiarrhoeal, diuretic and antilithic do contain a whole host of well- and lesser known compounds, e.g. iridoid glycosides, sitosterol, stigmasterol, campesterol, ursolic acid, hentriacontane, hentriacontanol, ceryl alcohol, palmitic acid and methyl mercaptan, but no diosgenin. So Ayurvedabol (TM) or whatever name ending on -bol, -drol or -ripp-off has not been used by the creepy competition, already, could benefit from having both Paederia foetida and Pedalium murex in it ;-)

• Combination of probiotics and phytosterols ramps up thyroid function and (re-)establishes a healthy lipid profile (Awaisheh. 2012) -- While I could offer you a minimum of two additional libido enhancing, potentially pro-anabolic testosterone booster, I know that not all of you are into these products (am I right ladies?), so I thought it prudent to close this installment of On Short Notice with a study on thyroid metabolism, which could be is of interested for all of you.
  
  
  Which phytosterols are there and where can I find them? The major phytosterols in the human diet are sitosterol (high in nuts, amaranth, avocados, grape leaves), stigmasterol (high in coriander, chocolate and soy), campesterol (high in various vegetable oils, spec. conola / rapeseed) and brassicasterol (high in cabbage, broccoli, other brassica, but also coriander, seafood and rapeseed oil).
  Contrary to some previous studies and anecdotal reports on the Internet, a recent paper by scientists from the Department of Food Science at the Al-Balqa Applied University, in Salt, Jordan, suggest that phytosterols don't have thyroid inhibiting, but promoting effects.
  
  In their latest study Awaisheh et al. investigated the effects of a probiotic stack containing two strains of each of Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus gasseri, and Lactobacillus reuteri and a phytosterol supplement on the lipid metabolism in rodents. Their results show that the addition of the phytosterol supplement promoted the already pronounced effects the probiotics had on the hypercholesterolemia of the rodents who were fed with a high-fat-high-cholesterol basal diet for 8 weeks. In addition, the phytosterols, yet not the probiotics alone, elevated the levels of serum total thyroxine (TT4), total triiodothyronine (TT3), and free triiodothyronin (fT3), which could have exerted additional benefits on the non-measured triglyceride levels.
  
  These results do actually come as a surprise and I would like to see more research - specifically in human trials - before I would buy products from producers who seize the scientists suggestion that this renders probiotics and phytosterols potential candidates for "functional foods" - I mean, let's be honest ever since the first "functional foods" hit the market people have been getting sicker: Do you really believe that's because they don't eat the "good" cholesterol lowering margarine instead of their beloved Kerrygold butter? I don't think so.

That's it for today.. well, aside from the promise to include the other testosterone and libido boosting herb studies in another SuppVersity post and a selection of the latest  SuppVersity Facebook News, of course:

• Iron deficiency makes H Pylori go on a rampage - Iron deficiency enhances H. pylori virulence and increases risk of gastric cancer (read more)
• Danish folk medicine for depression? Not really, but there are a couple of promising natural MAO-A inhibitors the Danes have been using for centuries (read more)
• Strength training equally heart healthy as aerobics - 6-weeks of strength training show particular beneficial effects in African American men (read more)

Since I it's still pretty early and I am certainly not going to the city, before the shops close and all the people who believed they wouldn't need Christmas presents this year, since the world would *put whatever apocalyptic catastrophe you like here*, have gone home, I may be adding some more news later. Until then, I hope you have some fun with what's already there and are looking forward for the 2nd installment of the "Making HIIT a Hit" series that will be published tomorrow.

References:

• Awaisheh SS, Khalifeh MS, Al-Ruwaili MA, Khalil OM, Al-Ameri OH, Al-Groom R. Effect of supplementation of probiotics and phytosterols alone or in combination on serum and hepatic lipid profiles and thyroid hormones of hypercholesterolemic rats. J Dairy Sci. 2012 Nov 22.
• Carani C, Rochira V, Faustini-Fustini M, Balestrieri A, Granata AR. Role of oestrogen in male sexual behaviour: insights from the natural model of aromatase deficiency. Clin Endocrinol (Oxf). 1999 Oct;51(4):517-24.
• Gao SG, Liu H, Li KH, Liu WH, Xu M, Jiang W, Wei LC, Zhang FJ, Tian J, Xiao WF, Yang Y, Song Y, Lei GH. Effect of Epimedium pubescen flavonoid on bone mineral density and biomechanical properties of femoral distal end and femoral diaphysis of passively smoking male rats. J Orthop Sci. 2012 May;17(3):281-8.
• Liu B, Zhang H, Xu C, Yang G, Tao J, Huang J, Wu J, Duan X, Cao Y, Dong J. Neuroprotective effects of icariin on corticosterone-induced apoptosis in primary cultured rat hippocampal neurons. Brain Res. 2011 Feb 23;1375:59-67. 
• Mangle MS, Jolley CI. HPTLC studies on Tribulus terrestris (Chota ghokru) and Pedalium murex (Bada ghokru). Indian Drugs. 1998; 35:189–194.
• MDidea Extracts Professional. Horny Goat Weed or Epimedium Herb: Botanical Origin, Archeology, Traditional and Pharmacological findings of Epimedium species, fractions and isolated components. 08th, Oct. 2010. < http://www.mdidea.net/products/herbextract/icariin/data10.html > retrieved on 12/21/2012. 
• Nan Y, Zhang X, Yang G, Xie J, Lu Z, Wang W, Ni X, Cao X, Ma J, Wang Z. Icariin stimulates the proliferation of rat Sertoli cells in an ERK1/2-dependent manner in vitro. Andrologia. 2012 Nov 7.
• Riggs BL, Khosla S, Melton LJ 3rd. A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res. 1998 May;13(5):763-73. 
• Sharma V, Thakur M, Dixit VK. A comparative study of ethanolic extracts of Pedalium murex Linn. fruits and sildenafil citrate on sexual behaviors and serum testosterone level in male rats during and after treatment. J Ethnopharmacol. 2012 Aug 30;143(1):201-6.
• Soni DK, Sharma V, Chauhan NS, Dixit VK. Effect of ethanolic extract of Paederia foetida Linn. leaves on sexual behavior and spermatogenesis in male rats
• Yan S, Wu B, Lin Z, Jin H, Huang J, Yang Y, Zhang X, Shen Z, Zhang W. Metabonomic characterization of aging and investigation on the anti-aging effects of total flavones of Epimedium. Mol Biosyst. 2009 Oct;5(10):1204-13.
• Zeng KW, Ko H, Yang HO, Wang XM. Icariin attenuates β-amyloid-induced neurotoxicity by inhibition of tau protein hyperphosphorylation in PC12 cells. Neuropharmacology. 2010 Nov;59(6):542-50.

Study Finds 17x Elevated Estrogen, High Progesterone + Reduced DHEA Levels in 65% of Ecdysteroid, Tribulus, Phytoestrogen, Phytosterol and / or Soy Protein Users!

Image 1 (Oliver Knöbel aka "Olivia Jones"): Not sure, but maybe the famous German drag artist Oilver Knöbel  aka "Olivia Jones" would be willing to buy some of your "all natural ergogenics"?

Tekin and Kravitz estimate the number of currently available "nutritional supplements" to be 30,000+ and if you want my personal estimate, roughly 30 of those are useful (Tekin. 2012). And while many of the other 29,970 supplements are often just dispensable, some are downright harmful or, as we have recently seen for alpha lipoic acid and zinc only beneficial for a certain, often sick, obese and diabetic part of the population (see "You are better of without alpha lipoic acid" and "Zinc supplements may cause insulin resistance & diabetes") and can - if taken in high doses or for long periods of time - become downright harmful for active physical culturists like you and me. The data Paolo Borrione and his colleagues from the Department of Health Sciences at the University of Rome present in a recently published paper does now confirm that ALA and zinc are probably still the most benign among the "potent ergogenics" and "all natural", "plant-derived nutritional supplements" that are specifically marketed to fitness enthusiasts all around the globe (Borrione. 2012).

Believe it or not: "Natural" and "non-hormonal" can be worse than synthetic and hormonal

Image 2: In view of the fact that ecdysteroids are meant to turn the guy on the left into the nasty bastard on the right, the guys in this study should be happy that they got away with hormonal imbalances ;-)

In their peer-reviewed observational pilot-study (I am already looking forward to the follow up ;-) the scientists queried 740 trained subjects (420 body builders, 70 cyclists, and 250 fitness athletes) over a 6-months period on their use of "commercially available plant-derived nutritional supplements", which contained any or several of the following ingredients

• ecdysteroids, 
• phytoestrogens, 
• phytosterols and/or
• tribulus terrestris

To my surprise only 26 of those 740 experienced trainees (all subjects have been training regularly for at least 1 year, 1–2 hours per day, 3–6 days per week) declared that they were currently using respective products, with

• In defense of at least some of the ingredients mentioned in this list to the left, it should be mentioned that it is not clear, if the observed effects were due to a single component of the supplements, due to several of the ingredients of an individual product or the highly undesirable and based on studies on isolated compounds non-predictable interactions. Personally, I would bet money that all three of these were involved, though.
  6 subjects consuming products that contained Caffeine, Citrus A., Zingiber, Guggul, Cacao, Naringine and Bioperine. 
• 6 subsect consuming products based on 5-Methyl-7Methoxyisoflavone, 7-Iso- propoxyisoflavone, 20-Hydroxyecdysone, Secretagogues, Triboxybol, Saw Palmetto extract, Beta Sitosterol, Pygeum extract, Guarana extract and Cordyceps extract. 
• 4 subjects consuming different dosages of a commercially available product containing Rhaponticum Carthamoides extract and (in one case) Ajuga Turkestanica and Rhaponticum Carthamoides root extract

for 6-12 months. The rest got at least a daily dose of phytoestrogens from soy protein products, some of which were enriched with Muira Puama and/or Guta Kola extracts - with highly detrimental consequences on the endocrine milieu for 15 (65%) of them.

Figure 1: Progesterone (ng/ml), estrogen (pg/ml) and DHEA (ng/ml) levels in users vs. non-users of "plant-derived nutritional supplements"; the bars for lower and upper indicate the lower and upper limit of the normal range, the figures on top of the blue bars are relative to the group average of the non-users (based on Borrione. 2012)

If your brain is not already malfunctioning due to too many "all natural ergogenics", it should be plain obvious that neither the 16x increase in estrogen, nor the 3x increase in progesterone are something you would be willing to pay money for. And that goes irrespective of whether you are a man or a women. After all,  these profound "hormonal alterations" (esp. the hyperestrogenism) could, as the scientists point out, lead to "severe health problems" such as

• gynecomastia, hypogonadism and reduced fertility in men, and 
• macromastia, enlarged uterus, menstrual irregularities and breast cancer in women.

In addition, hyperestrogenism represents a major risk factor for the female and male breast cancer (Heinig. 2002; Martin. 2003; Cederroth. 2010).

Taking DHEA or an "all natural" aromatase inhibitor will only exasperate the mess!

Image 2: Actually this post only confirms what I have been written in my previous post on "hormone optimization made simple and cheap". Avoiding all the natural and unnatural hormonal disruptors is the less expensive and healthiest way to optimize your endocrine system.

And while you could try to counter the reduced DHEA levels and the increase in estrogen by simply swallowing another pill (or a whole "stack"), I would suggest you better avoid all those totally natural, but by no means harmless test- or whatever boosters and suppressors of which Paolo Borrione et al. rightly state that they "have not been studied for long-term safety".

Contrary to the users in Berrione's study, of whom 45% did not even know all of the substances on the label of their supplement of choice you are now aware that the phytoestrogens, vegetal sterols and ecdysteroids are not simply not worth their money, they are more importantly not worth your health and should, just like the soy protein, which happens to be the one supplement that was on the list of every subject with abnormally elevated estrogen levels(!) never make it onto your supplement shopping list.

References:

1. Borrione P, Rizzo M, Quaranta F, Ciminelli E, Fagnani F, Parisi A, Pigozzi F. Consumption and biochemical impact of commercially available plant-derived nutritional supplements. An observational pilot-study on recreational athletes. J Int Soc Sports Nutr. 2012 Jun 19;9(1):28.
2. Cederroth CR, Auger J, Zimmermann C, Eustache F, Nef S: Soy, phyto-oestrogens and male reproductive function: a review. Int J Androl 2010, 33:304–316
3. Heinig J, Jackisch C, Rody A, Koch O, Buechter D, Schneider HP: Clinical management of breast concer in males: a report of four cases. Eur J Obstet Gynecol Reprod Biol 2002, 102:67–73.
4. Martin RM, Lin CJ, Nishi MY, Billerbeck AE, Latronico AC, Russell DW, Mendonca BB: Familial hyperestrogenism in both sexes: clinical, hormonal, and molecular studies of two siblings. J Clin Endocrinol Metab 2003, 88:3027–3034.
5. Tekin KA, Kravitz L: The growing trend of ergogenic drugs and supplements. ACSM’s Health Fitness J 2004, 8:15–18.

Want to Benefit from Plant Sterols? Eat Whole Food or Take Supplements With Meals. Plus: Do You "Benefit" at All?

This is not a joke by a blogger this is how Unilever advocates to use their Flora pro.active product to consumers, who "want to lower your cholesterol and follow a healthy diet and lifestyle."

Pharma companies and supplement producers are notorious for picking foods apart and providing you with concentrated extracts of the "active ingredients".

Aside from the fact that more often then not, the activity of those "active ingredients" is critically dependent on co-factors that are lost during the isolation and extraction processes, scientists from the Division of Gastroenterology-Hepatology at the Department of Internal Medicine of the Maastricht University Medical Center have now been able to show that the mere presence of the bulk in which plant sterols would come in the natural form is critically important to their effects.

Can you achieve a "healthily"(?) low cholesterol level by guzzling tuckloads of low-fat yogurt drinks!?

Based on the negative outcomes of previous studies into the benficial effect of "functional" foods or dietary supplements enriched in plant sterols, D. Keszthelyi had hypothesized  that

"100 mL drink, when consumed before a meal, would empty fast from the stomach and would not sufficiently trigger gallbladder emptying, whereas ingestion with or after the solid meal would enable the necessary physiological changes to aid inhibition of cholesterol absorption" (Keszthelyi. 2013)

To test this hypothesis the researchers recruited a total of 12 healthy male subjects (age, 25 ± 3 years; BMI, 23 ± 2 kg/m²) who reported the scientists' lab on three separate test days with one-week washout between test days.

Does the Paleo diet ruin your cholesterol levels as the conclusion to a recently published thesis would indicate (learn more)?

On each of the days, the participants consumed a Phytosterol (PS) containing yoghurt drink (100 mL, Becel Pro-Activ with PS added as their fatty acid esters (3.2 g, equivalent to 2.0 g PS), either

• 45 min before (test condition A), 

• during (test condition B), or

• 45 min after (test condition C) 

the consumption of a 500 g macaroni meal (Macaroni Bolognese, Henri, Drunen, The Netherlands) at lunch time (I know not the ideal, but for the average Westerner a realistic test meal). T

he sequence of the test days had been determined by a random pre-selection prior to the start of the study. During each test day, gastric emptying of the test drink as well as the effect of the test drink on gallbladder volumes were determined (figure 1, left):

Figure 1: Gastric emptying (left) and gallbladder volume (right) depending on the time of ingestion of a phytosterol containing yogurt drink (Keszthelyi. 2013)

As the results go to show you the ingestion of the functional food before the meal resulted in the fastest gastric emptying. The ingestion with or after a solid meal, on the other hand, caused a significant contraction of the gallbladder.

"Accepting the postulate that concurrent presence of PS with dietary and/or biliary cholesterol in the small intestine is an important mechanism for the LDL cholesterol-lowering action (Ostlung. 2004), a significant stimulus leading to gall- bladder contraction with simultaneous delivery of the PS-containing food format from the stomach into the duodenum is required. It is therefore important to ascertain which stimuli are able to elicit this postprandial response to a sufficient and desirable degree." (Keszthelyi. 2013)

This is actually interesting, because in the end it means that cholesterol clearance, even when it's induced / supported by questionable supplemental phytoestrogens critically depend on fat intake! This in turn would explain why the rodents in the "optimal diabesity diet study" from one of the recent installments of the Short News found elevated cholesterol levels only in the high sugar and high fat + high sugar groups, yet not in the rodents on a high fat diet.One thing to keep in mind, though: The main reason I picked and posted this study is not to pimp the use of phytosterol-spiked imho dys-functional junk food. It's rather to raise your awareness of the importance of the whole nutrient matrix in terms of the effects of the individual agent.

If you want to do something for your blood lipids, you better eat more eggs than overpriced Frankenfood. The eggs will not only improve your cholesterol particle profile, the regular consumption of whole eggs will also increase HDL's ability to carry lipids out of the macrophages. If these accumulate, they will turn the macrophage into pro-atherogenic foam cells (learn more).

In how far the isolation is also behind the previously observed side effects of plant sterols and stanols, which are likewise used in functional foods remains questionable, but it is not unlikely that sides such as

• abortion of pregnancy in animal models (Burckh. 1982)
• reduced sperm concentrations & testis weights
• neg. effects on the vascular system (Boberg. 1991)
• increased intestinal tumor formation (Marttinen. 2013)

are eventually also a consquence of the absence of important co-factors, when the sterols and stanols are removed from their original food matrix and "transplanted" into yogurts, margarines and all sorts of overly expensive and at best useless Frankenfoods.

References:

• Boberg KM, Pettersen KS, Prydz H. Toxicity of sitosterol to human umbilical vein endothelial cells in vitro. Scand J Clin Lab Invest. 1991 Oct;51(6):509-16.
• Burck PJ, Thakkar AL, Zimmerman RE. Antifertility action of a sterol sulphate in the rabbit. J Reprod Fertil. 1982 Sep;66(1):109-12. 
• Keszthelyi D, Knol D, Troost FJ, van Avesaat M, Foltz M, Masclee AA. Time of ingestion relative to meal intake determines gastrointestinal responses to a plant sterol-containing yoghurt drink. Eur J Nutr. 2013 Jun;52(4):1417-20.
• Ostlund RE Jr. Phytosterols and cholesterol metabolism. Curr Opin Lipidol. 2004 Feb;15(1):37-41.