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Some butter on top of the broccoli would allow for the assimilation of the absorption of the 101.6?g vitamin K 623IU vitamin A (various).

There are a handful of very basic questions in nutrition science, no one appears to have an answer to. One of these questions, which is directly related to the  well-known fact that the vitamins A, D, E & K are "lipid soluble". This means that they are "solved" and thus made absorbable by fats and oils. The general assumption is thus that the vitamins A, i.e. the retinol and carotenoids, all forms of vitamin D, the tocopherols and -trienols (vitamins E) and the two major forms of vitamin K, i.e. phylloquinone (K1) and menaquinone (K2) will only be absorbed, if you consume them with a sufficient amount of dietary fat. Now, the questions obviously are (a) is this correct and (b) how much is sufficient.
In view of the fact that the answers to (a) and be are not necessarily identical for all four vitamins of interest, it appears sensible to tackle them one after the other.


Starting with vitamin A and the various forms of carotenoids, we can already confirm that (a), i.e. the assumption that we need dietary fats to optimally absorb vitamin A is correct. As Karin van het Hof and her colleagues point out, the "amount of dietary fat required to ensure carotenoid absorption [does yet] seem low (?3–5 g per meal), although it depends on the physicochemical characteristics of the carotenoids ingested." (van het Hof. 2000) In spite of the fact that 5g of fat are not exactly much, the classic uncooked vegetarian orthorexic salad often comes with a total of only 5g of fat of which 95% remain at the bottom of the salad bowl. If that sounds like your favorite dish, you should be aware that you are risking that all the good  beta- and other carotenoids in the salad will pass right through.

Figure 1: Changes in hepatic vitamin A (retinol) and carotenoid stores in gerbils after 14 days on high fat (30%) vs. low fat (10%) diet (Deming. 2000)

In that, the concomitant presence of both dietary fat and carotenoids in a meal is a necessary prerequisite for the absorption of vitamin A, also because the fatty acids will trigger the conversion of of beta-carotene into vitamin A and its subsequent absorption via the lymphatic system (Ribaya?Mercado. 2002). It is thus not surprising that animal studies by Lakshman et al. (1996) and Deming et al. (2000; see Figure 1) suggest that low fat diet can lead to a depletion of the vitamin A tissue stores even if the serum levels remain constant. The amount of fiber in the diet, on the other, has no influence the absorption of vitamin A (Mills. 2009).

Interestingly enough, the provision of the fat blocker Orlistat reduces the absorption of vitamin A only insignificantly, as a 1996 paper by Angela T. Melia, Susan G. Koss?Twardy, and Jianguo Zhi would suggest (Melia. 1996).

Which takes us right to vitamin E, the absoprtion which is - in spite of being "blocked" by the fat blocker orlistat (Melia. 1996) - less susceptible to the absence of dietary fat than you may think. Annet JC Roodenburg, Rianne Leenen, Karin H van het Hof,  Jan A Weststrate, and Lilian BM Tijburg do in fact argue that the optimal intake of vitamin E requires only "a limited amount" of dietary fat (Roodenburg. 2000).

Figure 2: Vitamin E serum levels after 7 days on control (low fat, 3g) or high(er) fat (36g) diet with and without supplemental vitamin E (Roodenburg. 2000)

As you can see in Figure 2. A minimum intake of only 3g per day was sufficient to keep the vitamin E levels stable. The short study period of 7-days (each) and the absence of measures of tissue concentration of vitamin E do yet reduce the practical relevance of the data, Roodenburg et al. present in their Y2k paper in the American Journal of Clinical Nutrition.
If you take a look at the high prevalence of vitamin E dieficiency among the fat (and PUFA) "loving", or at least eating, majority of Americans, it does yet become obvious that a lack of dietary fat is not just theoretically, but also practically not exactly the #1 reason you may become deficient in tocopherols and -trienols. That the latter is an increased demand due to chronic inflammation and the (over-)consumption of exactly those PUFAs that come with a shitload of vitamin E in nature, for a reason would yet be a topic for another SuppVersity article and thus something we will skip to fast forward to ...

...Vitamin K, obviously. Vitamin K is a relative newcomer to the publics understanding of the alphabet soup. Aside from being it a good tool to rip customers vitamin K, or rather K1 (plant sources) and K2 (animal sources) are thus also the only fat soluble vitamins not everyone knows. The fact that the amount of phylloquinone (K1) that makes it into your blood stream is ~70% reduced if you eat your spinach without fat (Gijsbers. 1996).

And if we take the results researchers from the Gifu University School of Medicine present in a 1996 paper in the Journal of Pharmacological Sciences, as a reference, the amount of fat you need to optimally absorb your K2 (menaquinones), is not exactly low.

Figure 3: For optimal absorption of K2, there has got to be a huge amount of fat in the meal - but who wonders. K2 comes with a high amount of fat (Uematsu. 1996)

Uematsu et al. had to supply their subjects, who consumed otherwise identical test meals with 8.8, 20.0 and 34.9g of fat in them with the maximal (i.e. 35g) of fat before the K2 absorption maxed out. In that the total area under the curve did not really differ between those subjects who consumed the K2 before and those who took it immediately after the test meal.

Thats a pity, cause a high intake of vitamin K (menaquinone from animal sources) has been associated with a 27% reduced risk of developing heart disease (Geleijnse. 2004), an ailment of which many still believe that it was brought about by the fat they need to optimally absorb their vitamin K.

For vitamin D, our last "V" on the list, things look differently. For one, everybody knows about this miracle vitamin and for two, it may be "fat soluble", but the amount of fat thats required to optimally absorb it turned out to be much lower than previously thought (see "A Fat D-Ficiency! Do You Really Need More Vitamin D or Simply More Fatty Foods? Study Shows, Even 50.000 IU of Vitamin D3 Useless, When You Ingest It Without Fat. " | read more).
In fact, Niramitmahapanya et al. found in 2011 that its not necessarily a high amount, but rather the right type of fat that determines if and how much of the vitamin D you take in capsule form or find in comparably low amounts in your foods that determines how much of the vitamin D actually makes it into your bloodstream:

"The change in plasma 25OHD (nanograms per milliliter) during vitamin D supplementation was positively associated with MUFA, (? = 0.94; P = 0.016), negatively associated with PUFA, (? = ?0.93; P = 0.038), and positively associated with the MUFA/PUFA ratio (? = 6.46; P = 0.014)."

In plain English this means, that the "good" seed and vegetable oils with their high PUFA content will effectively inhibit the absorption of vitamin D - an observation that adds to the many reasons the modern sedentary, sun-avoiding, sun-screen using, soybean oil (MUFA:PUFA = 0.4) guzzling American is low in or  quasi devoid of vitamin D.

Figure 4: 25(OH)D levels of 30 healthy men and women after ingestion of 50.000IU vitamin D3 supplement in conjunction with a normal or low fat breakfast (Raimundo. 2011)

Against that background its not surprising that you will not find a conclusive answer to the question how much fat you actually need. In a study that used a fatty meal with soybean oil in it, the effect would be totally different from one in which the subjects consumed meals that were made with sunflower oil, an oil with a MUFA:PUFA ratio >1. In view of the results Gnadinger et al present in a recent appear it does still seem appropriate to consume at least some fat alongside your vitamin D supplements. As far as the food-borne vitamin D is concerned, you dont have to worry, anyways. Foods that are high in D3 usually come with all the fat you need to absorb it.

How much fat, exactly you would need to make the most of dietary and supplemental vitamin D, on the other hand, is still not known. The previously mentioned data from the study by Raimondo et al. (see Figure 4, to the right) I wrote about in "A Fat D-Ficiency" is obviously still valid. The extremely high amount of vitamin D (50,000IU!) could yet require a correspondingly high amount of fat to be optimally absorbed and the fact that the fat in the study came from a "vegetable margarine" with an undisclosed ratio of MUFA:PUFA does not make the real-world effects any more predictable.
References:

• Chitchumroonchokchai, Chureeporn, et al. "Dietary fats with increased ratio of unsaturated to saturated fatty acids enhance absorption of carotenoid and vitamin E by increasing both efficiency of micellarization and lipoprotein secretion." FASEB J 24 (2010): 539-3.
• Deming, Denise M., et al. "Amount of dietary fat and type of soluble fiber independently modulate postabsorptive conversion of ?-carotene to vitamin A in Mongolian gerbils." The Journal of nutrition 130.11 (2000): 2789-2796. 
• Geleijnse, Johanna M., et al. "Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study." The Journal of nutrition 134.11 (2004): 3100-3105.
• Gijsbers, Birgit LMG, Kon-Siong G. Jie, and Cees Vermeer. "Effect of food composition on vitamin K absorption in human volunteers." British Journal of Nutrition 76.02 (1996): 223-229.
• Goodman, Dew S., et al. "The intestinal absorption and metabolism of vitamin A and beta-carotene in man." Journal of Clinical Investigation 45.10 (1966): 1615.
• Jayarajan, P., Vinodini Reddy, and M. Mohanram. "Effect of dietary fat on absorption of ? carotene from green leafy vegetables in children." Indian journal of medical research 137.5 (2013).
• Kris-Etherton, P. M., et al. "Polyunsaturated fatty acids in the food chain in the United States." The American journal of clinical nutrition 71.1 (2000): 179S-188S.
• Lakshman, M. R., et al. "The effects of dietary taurocholate, fat, protein, and carbohydrate on the distribution and fate of dietary ??carotene in ferrets." (1996): 49-61.
• Melia, Angela T., Susan G. Koss?Twardy, and Jianguo Zhi. "The effect of orlistat, an inhibitor of dietary fat absorption, on the absorption of vitamins A and E in healthy volunteers." The Journal of Clinical Pharmacology 36.7 (1996): 647-653.
• van het Hof, Karin H., et al. "Dietary factors that affect the bioavailability of carotenoids." The Journal of nutrition 130.3 (2000): 503-506.
• Raimundo, Fabiana Viegas, et al. "Effect of high-versus low-fat meal on serum 25-hydroxyvitamin D levels after a single oral dose of vitamin D: a single-blind, parallel, randomized trial." International journal of endocrinology 2011 (2011).
• Ribaya?Mercado, Judy D. "Influence of Dietary Fat on ??Carotene Absorption and Bioconversion into Vitamin A." Nutrition reviews 60.4 (2002): 104-110.
• Roodenburg, Annet JC, et al. "Amount of fat in the diet affects bioavailability of lutein esters but not of ?-carotene, ?-carotene, and vitamin E in humans." The American journal of clinical nutrition 71.5 (2000): 1187-1193. 
• Uematsu, Toshihiko, et al. "Effect of dietary fat content on oral bioavailability of menatetrenone in humans." Journal of pharmaceutical sciences 85.9 (1996): 1012-1016.

"Go slow, grow fast" - does it really work this way?

I have to admit that I didnt have time to write "complete" article, so I will just work out an introduction and a bottom line to a never-finished draft that discusses an - in my humble opinion -  still unresolved question:  "Does the time under tension, which must not be confused with the simple number of reps let alone the set, matter when it comes to strength or muscle gains?"  As I said, based on my knowledge of the contemporary literature this is still an unresolved issue. Mostly, because slow (by necessity) means "light weight" and is hard / impossible to distinguish from the rep-number.

The methodological issues are probably also part of the reason that it would be an exaggeration to say that there are only "few" studies that investigate the influence of the time under tension (TUT) on hypertrophy or strength gains - but alas, I have collected the science-crumps for you. So here you go (for a preliminary list):

• Figure 1: Myofibrillar fractional protein synthesis (%/h; Burd. 2012)

  Low load + slow movement = high TUT ? increased protein synthesis -- The 175% increase in muscle protein synthesis in response to leg extensions that were performed with a TUT of 6s in the concentric, and 6s in the eccentric phase of the movement Nicholas A. Burd et al. report in their a 2012 paper in the Journal of Physiology is one of the is one of the few very concrete results from studies that were designed to isolate the effect of the time under tension (Burd. 2012).
  
  In view of the pathetic load (30% of the 1RM) and the matched volume, the practical relevance of these figures is yet highly questionable. For me personally, it is thus more surprising that the difference between ...
  
  • doing 12, 7 and 6 reps @ 30% of the 1 rep max to failure for 198±10 s 119±9 and 90±7s, respectively (SLOW condition w/ TUT of 606), and 
  • performing the same number of reps with the same weight, this time obviously not to failure, within 25±2s, 14±1s, and 11±1s, respectively,
  ...was not even more pronounced than the +/- 49% difference (175% vs. 126%) Burd et al. observed in their eight young male subjects after performin three sets of unilateral leg extensions. 
• Longer TUT, greater anaerobic energy expenditure - Inspite of the fact that it appears logical that longer times under tension would be associated with increases in energy expenditure, you as a SuppVersity reader know very well that not all things that exercise and nutrition science is not necessarily logical.
  
  In view of the overall scarcity of literature it is thus more than worth mentioning that Christopher B. Scotts 2012 study into the effects of time-under-tension and weight lifting cadence on aerobic, anaerobic, and recovery energy expenditures found that both, the anaerobic (=glyoclytic) energy expenditure and post energy oxygen consumption (EPOC) were significantly increased, when you train with a cadence of 4:1 or 1:4 and a corresponding TUT of 25s instead of 1.5:1 (TUT = 15s).

  Figure 2: Anaerobic energy expenditure, post exercise oxgen consumption and total energy expenditure (all in kJ) in the low TUT (1.5:1.5; 15s) vs. high TUT trials (Scott. 2012)

  It is thus only logical (you see, sometimes there is logic in exercise science ;-) that the total energy expenditure in the 25s TUT trials was ~30% higher than in the 15s TUT trial with its 1.5s up : 1.5 down cadence (see Figure 2).
  
  In view of the fact that the majority of us are hopefully not hitting the gym to "burn calories" (learn why thats simply dumb), these findings are interesting, but of similarly irrelevant as the previously cited increases in protein synthesis in the Burd study.
• Concentric tension time is key to muscle growth -- I know that broscience dictates otherwise, but the evidence from a human study by Gillies, Putman & Bell suggests just that: Its the concentric portion of the exercise that stimulates skeletal muscle hypertrophy in response to leg presses, parallel squats, knee extensions and knee flexions in 28 healthy young women with previous strength training experience (Gillies. 2006).

  Figure 3: Fiber area (µm²) of type I & II fibers before and after the 9-week training intervention (Gillies. 2006)

  As you can see in Figure 3, the baseline fibre size(s) of the subjects were yet so different that the participants that had been randomized to the group with an emphasis on the concentric phase (4:1 cadence) had an unfair growth advantage compared to the ladies in the eccentric emphasis group.
  
  In view of the fact that the eccentric emphasis group did also record greater strength gains, it appears unwarranted to change your training regimen from explosive / fast concentric vs. slow eccentric movements to the "concentric emphasis" pattern with its 4s : 1s cadence that was used in the study at hand. 
• Heavy and fast or "slow" and long - it does not even matter -- In 2006 and thus 6 years before the previously discussed study by Burd et al., Michiya Tanimoto and Naokata Ishii, two scientists from the University of Tokio conducted a similar, yet more realistic study which compared
  

  • Figure 4: Cross-sectional area of the knee extensor before (open bars) and after (solid bars) LST, HN, and LN exercise training for 12 wk (Tanimoto. 2006)

    a low-intensity training regimen [ 50% of onerepetition maximum (1RM)] with slow movement and tonic force generation (3 s for eccentric and concentric actions, 1-s pause, and no relaxing phase; LST), to a
  • a high-intensity training regimen ( 80% 1RM) with normal speed (1 s for concentric and eccentric actions, 1 s for relaxing; HN), and 
  • a low-intensity with normal speed training regimen (same intensity as for LST and same speed as for HN; LN)
  and found what most of you will probably already have expected: As far as muscle growth there was no difference to be seen between the LST and the HN regimen after 12 weeks. The LN = low-intensity, normal speed training on the other hand sucked was a total waste of time and did not increase the size of the quadriceps muscle that had been hammered with three sets thrice a week at all.

References: 

• Burd, N. A., Andrews, R. J., West, D. W., Little, J. P., Cochran, A. J., Hector, A. J., ... & Phillips, S. M. (2012). Muscle time under tension during resistance exercise stimulates differential muscle protein sub?fractional synthetic responses in men. The Journal of physiology, 590(2), 351-362. 
• Gillies, E. M., Putman, C. T., & Bell, G. J. (2006). The effect of varying the time of concentric and eccentric muscle actions during resistance training on skeletal muscle adaptations in women. European journal of applied physiology, 97(4), 443-453.
• Scott, C. B. (2012). The effect of time-under-tension and weight lifting cadence on aerobic, anaerobic, and recovery energy expenditures: 3 submaximal sets. Applied Physiology, Nutrition, and Metabolism, 37(2), 252-256. 
• Tanimoto, M., & Ishii, N. (2006). Effects of low-intensity resistance exercise with slow movement and tonic force generation on muscular function in young men. Journal of Applied Physiology, 100(4), 1150-1157.

Nigella sativa is available in form of seeds, oils and all sorts of ointments and for many of them there are studies suggesting that they work.

SuppVersity reader Amaan Mueen asks on Facebook: "In traditional Oriental medicine its said that blackseed is a cure for everything except death, is there any truth to that?" I probably dont give away too much, when I tell you that blackseed (also "black seed") aka "nigella sativa" is not going to cure everything, but death, but that does not mean that modern Western medicine has not been able to confirm what Oriental "doctors" have known for centuries.

In the following I am going to present an allegedly cursory overview of the existing evidence with a focus on those health benefits that could be relevant for the average and extra-ordinary SuppVersity reader.

• General anti-oxidant effects - The complete oil of N. sativa, as well as thymoquinone (the main compound of the essential oil) have been shown to significantly reduce non-enzymatic lipid peroxidation in liposomes (Houghton. 1995). Significant anti-oxidant effects have also been observed for other compounds isolated from N. sativa, uncluding thymoquinone, carvacol, t-anethole and 4-terpineol.
  
  

  Figure 1: The tymoquinone rich fraction of blackseed (TQRF-X) has dose dependent (L,M,H) effects on antioxidant enzyems in hypercholesterolemic (Ismail. 2010).

  These compounds were found in a series of other in vitro tests to have variable antioxidant, but no pro-oxidant properties.
  
  Most importantly, though, the different compounds in the oil were found to act in a synergistic manner (i.e. more than the mere summation of the actions of the individual compounds). This stresses the importance of using the whole oil (or the crude extract) of the seeds in pharmacological studies.
  
  As Ali and Blunden point out in their review of the literature, "the antioxidant property of N. sativa is multifactorial, [but] it does not seem to involve iron-complexing activity (Ali. 2003). It rather appears as if its general ability to scavenge free radicals, which may be, at least partially, the basis of many human diseases and conditions, could be at the heart of its ability to protect, for example, against CCl4 hepatotoxicity (Nagi. 1999), liver fibrosis and cirrhosis (Türkdogan. 2000), and hepatic damage induced by Schistosoma mansoni infection (Mahmoud. 2002).
• Antiinflammatory and analgesic actions -Its one thing to scavenge free radicals. Its yet a completely different thing to effectively reduce the inflammation thats often, but not always triggered by the presence of free radicals. Against that background its important to note that an aqueous extract from nigella sativa exhibits strong anti-inflammatory effects, as well (Al-Ghamdi, 2001). Using carrageenan-induced paw oedema as a model of inflammation, and the hot plate reaction time as a model of nociception, the extract was found to possess significant antiinflammatory and analgesic (=pain reducing) action.
  
  As Ali & Blunden (2003) point out, this finding lends some credence to the folk medicinal use of the plant as an antiinflammatory and analgesic substance, and also confirms previous reports on the antinociceptive (Abdel-Fattah. 2000) and antiinflammatory (Mutabagani. 1997) effects of N. sativa oil and its major component, thymoquinone, in mice.
  
  The possible mechanism by which N. sativa exerts its antiinflammatory action has been studied. Thymoquinone has been shown to be a potent inhibitor of eicosanoid generation, namely thromboxane B2 and leucotrienes B4, by inhibiting both cyclooxygenase and lipooxygenase, respectively (Houghton. 1995). Interestingly, it was found that the fixed oil of N. sativa had both antioxidant and anti-eicosanoid effects greater than thymoquinone, which is its active constituent (Houghton. 1995)

• Anti-Cancer Effect - In an in-vitro study from the late 1990s researchers from the Tobacco and Health Research Institute in Lexington were able to show that the thymoquinone (TQ) and dithymoquinone (DIM) content of nigella sativa have the astonishing ability to kill several parental and multi-drug resistant (MDR) human tumor cell lines (Worthen. 1997).
  

  Figure 2: A schematic diagram showing major molecular targets of TQ. As an anticancer agent, TQ inhibits the activity of CYP enzymes, which are involved in metabolic activation carcinogens, and induces the expression and activities of cytoprotective enzymes by activating Nrf2 signaling. TQ selectively induces tumor cell death in an ROS-dependent manner following both intrinsic and extrinsic pathways of apoptosis. TQ exerts anti-proliferative, anti-inflammatory, anti-migratory, anti-invasive and anti-metastatic effects by blocking the activation of NF-?B- and STAT3-regulated gene products (Kundu. 2014).

  In spite of the fact that there are as of yet no studies that show that humans were cured with blackseed, recent studies have shown that Thymoquinone, a component of Nigella sativa, decreases oxidative DNA damage in a rat model of mammary cancer (Sindi. 2014) and protect the brain, liver and other organs from radiation induced damage during cancer therapy (Ahlatci. 2014; Cikman. 2014). So, even if it were not for its established cytotoxic effects in various human cancer cells (e.g. Liver, Khan. 2014; Kidney, Tabasi. 2014; Prostate & Breast Cancer, Schneider-Stock. 2014; Cervix, Ichwan. 2014; etc.), it would still make sense to use black seed extracts as antioxidants during radiation and as studies indicate also chemotherapy (Pace. 2003; Almog. 2014).
• Anti-allergic effects - In a study from 2003 Kalus et al. observed significant reductions in subjective feeling of allergic symptoms in 152 patients with allergic diseases (allergic rhinitis, bronchial asthma, atopic eczema) who were treated with Nigella sativa oil, given in capsules at a dose of 40 to 80 mg/kg/day.
  
  

  Figure 3: The addition of blackseeds at a dosage of 2g/day propels the beneficial effects of subcutaneous allergen-specific immunotherapy on polymorphonuclear leukocyte (PMN) function in 24 patients sensitive to house dust mites with allergic rhinitis (I??k. 2010)

  Other studies confirm that Nigella sativa can reduce the peripheral blood eosinophil count, IgG1 and IgG2a, cytokine profiles and lung inflammation in murine model of allergic asthma (Abbas. 2004) that are equal to the corticosteriod dexamethasone and scientists from the Gaziosmanpasa University Medical Faculty say that "N. sativa display its antioxidant and regulatory effects via inflammatory cells rather than the host tissue (brain and medulla spinalis)" in a rodent model of experimental allergic encephalomyelitis (Ozugurlu. 2005). Effects that were also observed in a 2010 human study which indicates that "N. sativa seed supplementation during specific immunotherapy of allergic rhinitis may be considered a potential adjuvant therapy" (I??k. 2010 | see Figure 3).
• Anti-diabetes effects: The volatile compounds in nigella sativa oil have been shown to exert potent glucose lowering effects in healthy and diabetic animals (Al-Hader. 1993). Effects that occured in the absence of changes in insulin levels and are almost unsettlingly pronounced.
  

  Figure 4: Reduction in fasting blood glucose in the hours after the administration of 50mg/kg volatile oil extract to normal and diabetic rodents (Al-Hader. 1993).

  For those of you who are hovering around in the netherlands of glucose levels, anyway, the 14% reduction Al-Hader et al. observed in the healthy rabbits in their 1993 could in fact be enough to induce mild hypoglycemia and side effects such as ravenous appetite, feeling cold, cold sweat, being irritable and so on - an effect thats going to be particularly pronounced, because blacksee will at the same time inhibit the production of glucose in the liver that would otherwise compensate the drop in blood glucose (Al-Awadi. 1991).
  
  With comparatively lower doses of only 5ml of nigella sativa oil, Mohtashami et al. have recently demonstrated that the beneficial effects on blood glucose are not rodent specific.
  
  

  Figure 5: Blackseed consumed in 2x2.5ml servings everydy improves blood glucose management in healthy humans, too (Mohtashami. 2011)

  In their randomized clinical trial with 70 healthy subjects who received either 2.5 ml Black seed oil or a similarly looking mineral oil two times a day, the scientists observed achieved less pronounced, but still significant reductions in fasting blood glucose and the long(er)-term glucose marker HbA1c within only two months.
  
  In view of the comparatively small reductions in blood sugar (see Figure 5), its also not surprisng that the only side effect was an occasional case of transient nausea. Notable changes in liver enzyme and kidney functional adverse effects, on the other hand, were not observed..
  
  Similar results have been reported for subjects with diabetes (Najmi. 2008), intact and diabetic rats (Hawsawi. 2001; Houcher. 2007) and in several cell models, like muscle cells, where it increases AMPK and GLUT4 expression (Benhaddou-Andaloussi. 2011) or the Langerhans cells (Rchid. 2004) of the pancreas of which Fararh et al. (2002) were able to show that they can partly recover their ability to release insulin in a rodent model of diabetes, when nigella sativa is administered in conjunction with nicotinic acid.
• Cardiovascular effects - The results of a 2014 study by Mohammad et al. indicate that "[t]he use of N. sativa as an alternative therapy for hypercholesterolemia could have profound impact on the management of CVD among menopausal women especially in countries where it is readily available." In the corresponding study 1g of nigella sativa powder consumed after breakfast lead to significant improvements in lipid profiles of menopausal women (decreased total cholesterol, low density lipoprotein cholesterol and triglyceride, and increased high density lipoprotein cholesterol)within 2 months. Improvements that were lost almost completely after one month without the capped Nigella sativa supplement.
  
  Rather ambigous - at least at first sight - are the effects of nigella sativa on the physiology of the heart, while Al-Asoom et al. (2014a) were able to show that the IFG-1 boosting effects Nigella sativa exerts on exercising rats could make it a valuable tool for the treatment of heart failure with superior advantages to exercise training alone, the same effects are often mentioned as potential unwanted side effects of Nigella sativa.
  

  Figure 6: In trained rats, the Nigella sativa induced boost in IGF-1 (left) promotes the exercise induced increase in heart weight (right | Al-Asoom. 2014a)

  Whether thats actually a problem is yet questionable. In view of the nature of the cardiac hypertrophy, its rather an augmentation of the beneficial cardiac remodeling due to exercise similar to the one we call "athletes heart" than a pathological increase in the size of the heart. Whether similar effects can be observed for skeletal muscle has, at least as far as I know, yet not been tested - its yet certainly not impossible.

References

• Abbas, Ayman Talatt, et al. "Effect of dexamethasone and Nigella sativa on peripheral blood eosinophil count, IgG1 and IgG2a, cytokine profiles and lung inflammation in murine model of allergic asthma." The Egyptian journal of immunology/Egyptian Association of Immunologists 12.1 (2004): 95-102.
• Abdel-Fattah, Abdel-Fattah Mohamed, Kinzo Matsumoto, and Hiroshi Watanabe. "Antinociceptive effects of< i> Nigella sativa</i> oil and its major component, thymoquinone, in mice." European journal of pharmacology 400.1 (2000): 89-97. 
• Al-Saaidi, J. A. A., A. L. D. Al-Khuzai, and N. F. H. Al-Zobaydi. "Effect of alcoholic extract of Nigella sativa on fertility in male rats." Iraq J Verterin Sci 23 (2009): 123-8.
• Al-Asoom, L. I., et al. "Effect of Nigella sativa Supplementation to Exercise Training in a Novel Model of Physiological Cardiac Hypertrophy." Cardiovascular toxicology (2014a): 1-8. 
• Al-Asoom, Lubna Ibrahim, et al. "Comparison of Nigella sativa-and Exercise-Induced Models of Cardiac Hypertrophy: Structural and Electrophysiological Features." Cardiovascular toxicology (2014b): 1-6.
• Al-Awadi, Fatania, and U. Shamte. "The effect of a plants mixture extract on liver gluconeogenesis in streptozotocin induced diabetic rats." Diabetes research (Edinburgh, Scotland) 18.4 (1991): 163-168.
• Al-Hader, Aqel, M. Aqel, and Z. Hasan. "Hypoglycemic effects of the volatile oil of Nigella sativa seeds." Pharmaceutical Biology 31.2 (1993): 96-100.
• Ali, B. H., and Gerald Blunden. "Pharmacological and toxicological properties of Nigella sativa." Phytotherapy Research 17.4 (2003): 299-305. 
• Ahlatci, Adem, et al. "Radiation-modifying abilities of< i> Nigella sativa</i> and Thymoquinone on radiation-induced nitrosative stress in the brain tissue." Phytomedicine 21.5 (2014): 740-744. 
• Benhaddou-Andaloussi, Ali, et al. "The in vivo antidiabetic activity of Nigella sativa is mediated through activation of the AMPK pathway and increased muscle Glut4 content." Evidence-Based Complementary and Alternative Medicine 2011 (2011).
• Cikman, Oztekin, et al. "Radioprotective Effects of Nigella Sativa Oil Against Oxidative Stress in Liver Tissue of Rats Exposed to Total Head Irradiation." Journal of Investigative Surgery (2014).
• Fararh, K. M., et al. "Isulinotropic properties of< i> Nigella sativa</i> oil in Streptozotocin plus Nicotinamide diabetic hamster." Research in veterinary science 73.3 (2002): 279-282.
• Hawsawi, Zubaida A., Basil A. Ali, and Abdullah O. Bamosa. "Effect of Nigella sativa (black seed) and thymoquinone on blood glucose in albino rats." Annals of Saudi medicine 21.3-4 (2001): 242-244. 
• Houcher, Zahira, et al. "Effects of methanolic extract and commercial oil of Nigella sativa L. on blood glucose and antioxidant capacity in alloxan-induced diabetic rats." Pteridines 18.1 (2007): 8-18.
• Houghton PJ, Zarka R, de las Heras B, Hoult JRS."Fixed oil of Nigella sativa and derived thymoquinone inhibit eicosanoid generation in leukocytes and membrane lipid peroxidation". Planta Med 61 (1995): 33–36.
• Ichwan, S. J., et al. "Apoptotic Activities of Thymoquinone, an Active Ingredient of Black Seed (Nigella sativa), in Cervical Cancer Cell Lines." The Chinese journal of physiology 57.5 (2014).
• Lautenbacher LM. "Schwarzkümmelöl." Dtsch Apoth Ztg 137 (1997): 68–69.
• Khan, Fazal, et al. "Evaluation of the effect of Nigella sativa extract on human hepatocellular adenocarcinoma cell line (HepG2) in vitro." BMC Genomics 15.Suppl 2 (2014): P63.
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• Mohtashami, R., et al. "Blood Glucose Lowering Effects of Nigella Sativa L. Seeds Oil in Healthy Volunteers: a Randomized, Double-Blind, Placebo-Controlled Clinical Trial." Journal of Medicinal Plant 10.36 (2011): 90-94.
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If you dont see any results, changing the angle, grip, etc. is unlikely to bring you from "zero" to "extreme" gains.

I dont need a scientific study to tell that the bench press is among the favorite exercises of all (male) trainees. That being said, the science investigating its effects and how to do it is comparably scarce. Leg extensions are after all the favorite exercise of every researcher, because even sedentary couch potatoes can do them and the results dont depend on your "extension technique" ;-)

That being said, there are a handful of studies dealing with the bench press. Studies that investigate the effects of bench angles, grip width & type, free weight vs. machine training, training to failure or not, etc. a selection of which I will review in todays SuppVersity article.

• Is there a place for the incline bench press in your routine? According to data from a 1995 study from the University of Queensland, it would seem the answer is "unlikely". In the corresponding experiment, Barnett et al. investigated the effects of varying bench inclination on the EMG activity of five muscles acting at the shoulder joint.
  
  Six male weight trainers performed presses under four conditions of trunk inclination and two of hand spacing at 80% of their predetermined max. Preamplified surface EMG electrodes were placed over the five muscles in question. The EMG signals during the 2-sec lift indicated some significant effects of trunk inclination and hand spacing (see Figure 3, as well).
  

  Figure 1: As you can see, the deltaoid muscles take over, as the angle increases (left), when it decreases significantly, i.e. on the decline bench, on the other hand, the latissimus dorsi (right) is suddenly involved (Barnett. 1995).

  More specifically, the sternocostal head of the pectoralis major, or the "middle part of the pecs" as the bros would say, was more active during the press from a horizontal bench than from a decline bench. Since the clavicular head of the pectoralis major, or the "upper part of the pecs", was no more active during the incline bench press (where the delts "shouldered" much of the exercise) than during the horizontal one, and was less active during the decline bench press, it would appear as if doing incline benches is at best something you can do on top of the regular press.
  
  On the other hand, we are - once more - lacking data on the long-term effects of benching on a flat vs. incline bench, which is why I cannot guarantee that changing things up from time to time is not eventually going to give you the best results. Or, as Barnett et al. point out: "Any benefits of varying the bench inclination for the pectoralis major are more likely due to psychological or biological factors (other than the quantity of EMG activation)" (Barnett. 1995).
• Is benching with a slightly wider than shoulder wide grip still the way to go? The purpose of this study from the University of Southwestern Louisiana was to determine the effect of grip width on myoelectric activity of the pectoralis major, anterior deltoid, triceps brachii, and biceps brachii during a 1-RM bench press. Put simply, Clemons et al. wanted to know if using different grip widths would have the triceps, biceps or deltoid do more and the pecs less work.
  
  

  Figure 2: Like most people this guy benches with ~125% of the biacromial breadth (distance from the outer part of the shoulder on the left to the outer part of the shoulder on the right).

  Grip widths of 100,130,165, and 190% (G1, 2, 3, 4, respectively) of biacromial breadth were used in the study. Mean integrated myoelectric activity for each muscle and at each grip width was determined for the concentric portion of each 1-RM and normalized to percentages of max volitional isometric contractions (%MVIC). Data analysis employed a one-factor (grip width) univariate repeated measures ANOVA.

• The results of the study indicate that (a) the grip width you select will have significant main effects on muscle activity (3%, 5% and 8% increased maximal volutional isometric contractions with 30%, 65% and 90% increased grip width vs. should width) and that (b) that this difference was particularly pronounced (surprise ;-) when comparing 190% to 100% and 100%. More specifically, the involvement of the triceps increased, as the grip narrowed. Simlarly, a study by Barnett et al. (1995) indicates that the middle of the pecs major was more active with a narrower hand spacing.
  

  Figure 3: As a study by Barnett et al. indicates the effects of grip width on the absolute activity of the sternocostal head (middle pecs) is negligible (Barnett. 1995).

  Since EMG measures dont necessary translate to gains, these observations do not mean, though, that the wide bench press was the best chest builder (read all SuppVersity EMG Articles). To confirm that wed need long-term studies on the actual growth effect, which are unfortunately lacking.
• Are free weights always the better choice? Common wisdom has it that nothing compare to free weight training. A claim that is supported, but not fully confirmed by a 1994 study from the Illinois State University which shows that greater muscle activity is in fact achieved during the free-weight bench press, especially at the 60% 1-RM load.

  Figure 4: Comparison of the muscle activity during free weight and machine guided bench presses - please not that the differences reached significant only for the low = 60% 1RM weight (McCaw. 1996).

  What is quite noteworthy, though, is that (a) few people bench at only 60% of their 1-RM which would allow them to do at least 15 reps if not more and (b) that there were notable differences among the patterns of individual subjects.
  
  It is thus questionable that (1) the free-weight bench press is vastly superior to benching on a guided machine and that (2) this is the case for everyone - specifically in rookies, I could imagine that they get more out of the benching on a machine... One should keep in mind, however, that if you never bench with free weights, how will hardly learn how to do it properly to eventually benefit from the increased muscle activation.
  

  Figure 4: Free weight bench presses have the edge over the smith machine, in terms of avg. pec activity, but the differences are highly variable individual and dont reach statistical significance (Schick. 2010).

  In view of the fact that a similar study by Schick et al., which otherwise confirms the results of the study at hand observing increased activity of the stabilizer and measurable, but non-significantly increased pectoralis activity on free weight vs. machine bench presses (see Figure 5), indicates that the advantage of free weight vs. guided smith machine bench presses increases in experienced vs. rookie weight lifters, thatd be a bummer.
• Going to failure on the bench - is that useful or bogus? According to the results of a 2005 study from the ACT in Cranberra, bench press training that leads to repetition failure induces greater strength gains than nonfailure training in the bench press exercise for elite junior team sport athletes.
  
  As you can see in Figure 5, the differences that were observed in response to thrice weekly bench press training for 6 weeks using equal volume programs (24 reps, 80-105% 6RM in 13 minutes 20 seconds) in 26 elite junior male basketball and soccer players with a history of greater than 6 months’ strength training were significant, but not exuberant.
  

  Figure 5: Effects of training to failure on bench throw (left) and bench press 6RM (right) in soccer and basketball players (Drinkwater. 2005).

  The results of previous studies on training to failure are ambigous, by the way. Rooney et al. (1994), for example demonstrated that when a 6RM load is lifted repeatedly 6 times without resting between repetitions, the strength gains are significantly greater than when the same load is lifted an equal number of times with a 30-second interval between each lift to avoid fatigue. He suggested that when the athlete is fatigued, additional motor units are recruited in an attempt to continue the muscular activity, and this is thought to provide an additional stimulus for strength gains and hypertrophy.
  
  Other studies have shown, on the contrary, that training to failure may not be necessary for optimal gains, but they were not controlled for volume and intensity (Kramer. 1997; Stowers. 1983). In his 2010 review Schoenfeld argues that the possible increase in strength and size gains is also paid for with an increase in overtraining and injury risk. It is thus still not clear, whether training to failure is necessarily beneficial for all or should be used only by certain athletes and/or training phases.
• Do exaggerated eccentrics increase your strength gains on the bench? "Yes, it does!" - thats an answer researchers from the Ball State University would probably give to the question. In their 2002 study, the scientists examined the effects of additional eccentric loading on subsequent concentric strength.
  
  

  Figure 6: The data in the graph on the top indicates that the patented weight-release devices provide additional eccentric loading and are released at the bottom of the bench press before the concentric phase (Doan. 2002)

  Eight subjects with some experience in weight training volunteered to perform maximal attempts in the barbell bench press using detaching hooks that allowed them to lower 105% of their concentric 1 repetition maximum (RM) and raise 100%. The detaching hooks allowed attachment of extra weight to the bar and would release from the bar at the bottom of the lift, reducing the weight lifted during the concentric phase of the lift. After determining their 1RM for the bench press, the subjects attempted to increase their performance by using a heavier eccentric load with the detaching hooks.
  
  All 8 subjects who completed the study increased their 1RMs by 5 to 15 pounds; and as the data in Figure 8 indicates, the use of additional eccentric loading significantly (p 5 0.008) increased the weight that could be lifted on the subsequent concentric phase and therefore 1RM performance. As the researchers point out "[t]his phenomenon was a result of the enhancement of stretch-shortening cycle performance by the increased eccentric load" (Doan. 2002).
  
  Athletes who are interested in developing 1RM strength in the bench press may thus as the study and hand indicates benefit from the use of additional eccentric loading.

References:

• Barnett, Chris, Vaughan Kippers, and Peter Turner. "Effects of Variations of the Bench Press Exercise on the EMG Activity of Five Shoulder Muscles." The Journal of Strength & Conditioning Research 9.4 (1995): 222-227.
• Clemons, James M., and Chantelle Aaron. "Effect of Grip Width on the Myoelectric Activity of the Prime Movers in the Bench Press." The Journal of Strength & Conditioning Research 11.2 (1997): 82-87.
• Doan, Brandon K., et al. "Effects of increased eccentric loading on bench press 1RM." The Journal of Strength & Conditioning Research 16.1 (2002): 9-13.
• Drinkwater, Eric J., et al. "Training leading to repetition failure enhances bench press strength gains in elite junior athletes." The Journal of Strength & Conditioning Research 19.2 (2005): 382-388.
• Keogh, Justin WL, Greg J. Wilson, and Robert E. Weatherby. "A Cross-Sectional Comparison of Different Resistance Training Techniques in the Bench Press." The Journal of Strength & Conditioning Research 13.3 (1999): 247-258.
• Kramer, James B., et al. "Effects of single vs. multiple sets of weight training: Impact of volume, intensity, and variation." The Journal of Strength & Conditioning Research 11.3 (1997): 143-147.
• Lehman, Gregory J. "The influence of grip width and forearm pronation/supination on upper-body myoelectric activity during the flat bench press." The Journal of Strength & Conditioning Research 19.3 (2005): 587-591.
• McCaw, Steven T., and Jeffrey J. Friday. "A Comparison of Muscle Activity Between a Free Weight and Machine Bench Press." The Journal of Strength & Conditioning Research 8.4 (1994): 259-264.
• Rooney, Kieran J., Robert D. Herbert, and Ronald J. Balnave. "Fatigue contributes to the strength training stimulus." Medicine & Science in Sports & Exercise 26 (1994): 1160-4.
• Schick, Evan E., et al. "A comparison of muscle activation between a Smith machine and free weight bench press." The Journal of Strength & Conditioning Research 24.3 (2010): 779-784.
• Schoenfeld, Brad J. "The mechanisms of muscle hypertrophy and their application to resistance training." The Journal of Strength & Conditioning Research 24.10 (2010): 2857-2872.
• Stowers, Tim, et al. "The Short-Term Effects of Three Different Strength-Power Training Methods." Strength & Conditioning Journal 5.3 (1983): 24-27.