Stand on one foot with the arch and heel hanging off of the edge of a step or platform. Hold onto something if you need help balancing. Drop your heel all the way down below the step, and then rise all the way up on your toes. Hold dumbbells to make it harder. If you can balance without holding on to something, you’ll work your core muscles, too. You'll also build more stable joints in the other leg.

Mr. Olympia is part of the International Federation of Bodybuilding Professional League. The I.F.B.B. says that it operates under the guidelines of the World Anti-Doping Agency and that competitors are subject to drug testing. Chang, who oversees the Mr. Olympia contest, said that I.F.B.B. testing is random, but is not conducted during the Mr. Olympia contest itself.

A meta-analysis found that creatine treatment increased muscle strength in muscular dystrophies, and potentially improved functional performance.[57] Creatine treatment does not appear to improve muscle strength in people who have metabolic myopathies.[57] High doses of creatine lead to increased muscle pain and an impairment in activities of daily living when taken by people who have McArdle disease.[57]
Mitochondrial myopathies are a subgroup of mitochondrial cytopathies in which the skeletal muscle is negatively influenced. They are characterized by weaknesses in muscular function and energy metabolism.[547] These particular myopathies are thought to benefit from creatine supplementation, since creatine can help with some of the dysregulated energy production.[548]

Creatine has been noted to increase the amplitude (0.5-5mM) and frequency (25mM only) of NMDA receptors, although concentrations of 0.5-25mM also reduced signaling intensity. This was credited to creatine causing an increase in ligand binding of glutamate with an EC50 of 67µM and maximal activity at 1mM creatine (158±16% of baseline).[214] Creatine appears to modulate the polyamine binding site of the NMDA receptor, as it is abolished by arcaine and potentiated by spermidine.[215] This binding site is known to modify NMDA receptor affinity.[216][217]

Whenever you hear the word, “bodybuilding”, your mind usually flashes you images of bulging muscles, steel, sweat, the shouts of weightlifters, and ripped, muscular bodies of men and women in skimpy spandex. Your mind instantly takes you to the gym followed by wishful thinking that you can have a sexy body and bigger muscles. However, it takes more than just

This suppression of creatine synthesis is thought to actually be beneficial, since creatine synthesis requires s-adenosyl methionine as a cofactor and may use up to 40-50% of SAMe for methylation[35][36][122] (initially thought to be above 70%, but this has since been re-evaluated[122]) though the expected preservation of SAMe may not occur with supplementation.[487] Reduced creatine synthesis, via preserving methyl groups and trimethylglycine (which would normally be used up to synthesize SAMe), is also thought to suppress homocysteine levels in serum,[37] but this may also not occur to a practical level following supplementation.[487]
Prohormones are precursors to hormones and are most typically sold to bodybuilders as a precursor to the natural hormone testosterone. This conversion requires naturally occurring enzymes in the body. Side effects are not uncommon, as prohormones can also convert further into DHT and estrogen. To deal with this, many supplements also have aromatase inhibitors and DHT blockers such as chrysin and 4-androstene-3,6,17-trione. To date most prohormone products have not been thoroughly studied, and the health effects of prolonged use are unknown. Although initially available over the counter, their purchase was made illegal without a prescription in the US in 2004, and they hold similar status in many other countries. They remain legal, however, in the United Kingdom and the wider European Union. Their use is prohibited by most sporting bodies.

Still, it's important to realize that for everyone, at a certain point, building muscle becomes more difficult. "We all have an endpoint to our genetic potential," Matheny says. "Someone who is starting strength training for the first time can build muscle with a lower percentage of their 1RM [the maximum amount of weight they can lift one time] than a more tenured athlete. The longer you train and the closer you to get to your natural potential, the more specific you need to get with your training and nutrition to keep making progress. And that week-by-week progress will likely be much smaller than it once was."

Generally, you should consume about 20 grams of protein with some carbs shortly after a workout. During the post-workout anabolic window, you’ll also want to limit fats, which can slow the absorption of protein. While there is some recent research that suggests the window may actually extend up to several hours following exercise, there’s no harm in getting nutrients in early as long as you’re sticking to your overall caloric and macronutrient goals.

Brain injury. Early research shows that taking creatine by mouth daily for 7 days increases the ability to exercise by increasing lung function in people with a spinal cord injury. However, other research shows that creatine does not improve wrist muscle or hand function. Early research also shows that taking creatine by mouth daily for 6 months reduces amnesia following a traumatic brain injury in children.
Don’t take sets to the point of failure—where you absolutely can’t perform another rep. You should never get to where you’re turning purple and screaming like you’re getting interviewed by “Mean” Gene Okerlund before WrestleMania. Most of the time, you want to end your sets two reps before total failure. Not sure when that is? The moment your form breaks down, or you’re pretty sure it’s going to break down, end the set.
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Site enhancement oil, often called "santol" or "synthol" (no relation to the Synthol mouthwash brand), refers to oils injected into muscles to increase the size or change the shape. Some bodybuilders, particularly at the professional level, inject their muscles with such mixtures to mimic the appearance of developed muscle where it may otherwise be disproportionate or lagging.[54] This is known as "fluffing".[55][56] Synthol is 85% oil, 7.5% lidocaine, and 7.5% alcohol.[55] It is not restricted, and many brands are available on the Internet.[57] The use of injected oil to enhance muscle appearance is common among bodybuilders,[58][59] despite the fact that synthol can cause pulmonary embolisms, nerve damage, infections, sclerosing lipogranuloma,[60] stroke,[55] and the formation of oil-filled granulomas, cysts or ulcers in the muscle.[59][61][62] Rare cases might require surgical intervention to avoid further damage to the muscle and/or to prevent loss of life.[63]
The high levels of muscle growth and repair achieved by bodybuilders require a specialized diet. Generally speaking, bodybuilders require more calories than the average person of the same weight to provide the protein and energy requirements needed to support their training and increase muscle mass. In preparation of a contest, a sub-maintenance level of food energy is combined with cardiovascular exercise to lose body fat. Proteins, carbohydrates and fats are the three major macronutrients that the human body needs in order to build muscle.[24] The ratios of calories from carbohydrates, proteins, and fats vary depending on the goals of the bodybuilder.[25]
Weight trainers commonly spend 5 to 20 minutes warming up their muscles before starting a workout. It is common to stretch the entire body to increase overall flexibility; however, many people stretch just the area being worked that day. The main reason for warming up is injury prevention. Warming up increases blood flow and flexibility, which lessens the chance of a muscle pull or joint pain.

Include cardio training. Good cardiovascular health improves blood flow, a requirement for muscle growth. Doing cardio also improves your cardiovascular fitness, which allows you to use your muscle gains for various sports and activities. The standard recommendation is 150 minutes of moderate cardio each week, or 75 minutes of vigorous cardio, or an equivalent combination of the two. A good place to start would be doing 30-60 minutes of cardiovascular activity every other day or 3 times a week. Examples of cardio include running, biking, swimming, and any sport that involves constant movement.

Transparent Labs’ Creatine HMB really did their homework. The HMB, which stands for hydroxymethylbutyrate, is the main metablite in the branched chain amino acid leucine that prevents the breakdown of muscle protein. Translation: it helps you to retain muscle, and it appears to do so more effectively than leucine alone. One bonus is that combining HMB with creatine also appears to increase strength better than taking either supplement alone. Plus, the blue raspberry flavor is delicious and contains no artificial sweeteners.
A double-blind study provided 20 g/day of creatine monohydrate for 5 days to qualified sprinters and jumpers who performed 45 seconds of continuous jumping and 60 seconds of continuous treadmill running. Supplementation enhanced performance in the jumping test by 7% for the first 15 seconds and 12% for the next 15 seconds, but there was no difference for the final 15 seconds. There was a 13% improvement in the time of intensive running to exhaustion [12].
Nephrectomized rats may have significantly reduced creatine synthesis rates[509] via impairment of methylation (the GAMT enzyme)[510] although creatine reuptake from the urine seems unimpaired.[511] Supplemental creatine in a rat model of 2/3rds nephrectomy (2% creatine in the diet) does not appear to negatively influence kidney function as assessed by the serum biomarkers of cystatin C and urinary protein or creatinine clearance rates.[512] Elsewhere, 2% creatine in the diet in rats for two weeks again failed to show negative effects on kidney function, but showed benefit in reducing homocysteine in late-stage uremic rats.[312] While there is not much human evidence for the rat nephrectomy model, a lone case study in a man with a single kidney failed to find an impairing effect of creatine (20g daily for five days and 5g for another month) in conjunction with a high protein diet.[513]
The majority of studies focusing on creatine supplementation report an increase in the body’s’ creatine pool [15-17]. There is a positive relationship between muscle creatine uptake and exercise performance [17]. Volek et al [18] observed a significant increase in strength performance after 12 weeks creatine supplementation with a concurrent periodized heavy resistance training protocol. The creatine supplementation protocol consisted of a weeklong loading period of 25 g/d followed by a 5 g maintenance dose for the remainder of the training. These positive effects were attributed to an increased total creatine pool resulting in more rapid adenosine triphosphate (ATP) regeneration between resistance training sets allowing athletes to maintain a higher training intensity and improve the quality of the workouts along the entire training period.
When creatine supplementation is combined with heavy resistance training, muscle insulin like growth factor (IGF-1) concentration has been shown to increase. Burke et al [2] examined the effects of an 8 week heavy resistance training protocol combined with a 7 day creatine loading protocol (0.25 g/d/kg lean body mass) followed by a 49 day maintenance phase (0.06 g/kg lean mass) in a group of vegetarian and non-vegetarian, novice, resistance trained men and women. Compared to placebo, creatine groups produced greater increments in IGF-1 (78% Vs 55%) and body mass (2.2 Vs 0.6 kg). Additionally, vegetarians within the supplemented group had the largest increase of lean mass compared to non vegetarian (2.4 and 1.9 kg respectively). Changes in lean mass were positively correlated to the modifications in intramuscular total creatine stores which were also correlated with the modified levels of intramuscular IGF-1. The authors suggested that the rise in muscle IGF-1 content in the creatine group could be due to the higher metabolic demand created by a more intensely performed training session. These amplifying effects could be caused by the increased total creatine store in working muscles. Even though vegetarians had a greater increase in high energy phosphate content, the IGF-1 levels were similar to the amount observed in the non vegetarian groups. These findings do not support the observed correlation pattern by which a low essential amino acid content of a typical vegetarian diet should reduce IGF-1 production [33]. According to authors opinions it is possible that the addition of creatine and subsequent increase in total creatine and phosphocreatine storage might have directly or indirectly stimulated production of muscle IGF-I and muscle protein synthesis, leading to an increased muscle hypertrophy [2].
Focus on form. Good form means you can reap all of the benefits of your workout and avoid injuries at the same time. To maintain proper form, pay attention to your posture (stand tall with chest lifted and abs held tight), move slowly (this ensures you're relying on muscles, not momentum, to do the lifting), and remember to breathe. Many people hold their breath while exerting, but exhaling during the hardest part of the exercise helps fuel the movement.
Perform bent over rows to work your back. Stand with your feet shoulder-width apart, about 6 to 10 inches (15–25 cm) behind the barbell or two dumbbells. Bend slightly at the knees but keep your shins vertical. Bend forward at the waist with your spine and head straight. Lift the weight with an overhand grip up to your lower chest or upper abdomen. Lower slowly until your arms are nearly extended, without touching the ground. 3 x 8.[5]
A 2001 study at the University of Texas found that lifters who drank a shake containing amino acids and carbohydrates before working out increased their protein synthesis more than lifters who drank the same shake after exercising. The shake contained 6 grams of essential amino acids — the muscle-building blocks of protein — and 35 grams of carbohydrates.
Getting comfortable with a steady running routine is definitely something to be proud of, but when you're on that cardio grind day-in and day-out, you might be ready to change things up and take on a new challenge. Time to throw some strength training into the mix. It can be a little intimidating at first if you don't know where the hell to start, but understanding the basics can help you feel confident in your refreshed fitness routine.
The creatine transporter is a sodium[139][140] and chloride[141][142] dependent membrane-associated transporter that belongs to the Na+/Cl-dependent family of neurotransmitter transporters.[143] In muscle cells and most other cell types,[131][141] the isomer of the creatine transporter is known as SLC6A8 (solute carrier family 6, member 8). SLC6A8 is encoded by the gene present on the Xq28 region of the human X-chromosome and is expressed in most tissues.[144] A related gene encoding a creatine transporter variant has also been identified at 16p11.1 that is expressed exclusively in the testes.[145] These two transporters share 98% homology.[144][145]
When creatine is increased in the fetus (from maternal supplementation of 5% creatine), the fetus has a greater chance of survival and increased growth rates to a level not significantly different than vaginal birth.[531] Protection from hypoxia has also been noted in the offspring’s diaphragm (through preserved muscle fiber size),[533] kidneys,[534] and neural tissue (due to less oxidation in the brain and less cellular apoptosis).[535]
You should be keeping whichever program you are doing to no more than 1 hour of duration. Be sure that you are focusing on keeping the intensity high rather than making the workout drag on. Plus, there's no research that says marathon training sessions are better for muscle growth. Focus on keeping your rest periods under a minute and limit the small talk with other gym members.

There are several ways to enhance the quality of a workout, and some changes can even be made during each rep. “Constant tension should be applied to the last five reps of every working set, meaning, do the first 5-6 reps normal tempo, and the last few reps should be held for at least two seconds at the peak of the contraction,” says Heath. “This allows your muscles to have more time under tension and you work different muscle fibers.” Hold the weight at the top for a maximum pump.
This is another thing I am very tired of hearing. 'No matter what I do or what I eat, I can't gain weight'. I have heard this countless times and I am here to tell you that you are dead wrong. That's OK, because I actually said the same thing until I realized the truth. Most people think they are eating a lot and you just may be. But no matter what you are eating, if you are not gaining, you are not eating enough. Most times, you should re-evaluate your diet as well and focus on more calorie dense foods. But you need to eat more if you are not gaining.
There have been a few reported renal health disorders associated with creatine supplementation [73,74]. These are isolated reports in which recommended dosages are not followed or there is a history of previous health complaints, such as renal disease or those taking nephrotoxic medication aggravated by creatine supplementation [73]. Specific studies into creatine supplementation, renal function and/or safety conclude that although creatine does slightly raise creatinine levels there is no progressive effect to cause negative consequences to renal function and health in already healthy individuals when proper dosage recommendations are followed [73-77]. Urinary methylamine and formaldehyde have been shown to increase due to creatine supplementation of 20 g/d; this however did not bring the production outside of normal healthy range and did not impact on kidney function [56,78]. It has been advised that further research be carried out into the effects of creatine supplementation and health in the elderly and adolescent [73,75]. More recently, a randomized, double blind, 6 month resistance exercise and supplementation intervention [79] was performed on elderly men and women (age >65 years) in which subjects were assigned to either a supplement or placebo group. The supplement group was given 5 g CM, 2 g dextrose and 6 g conjugated linoleic acid/d, whilst the placebo group consumed 7 g dextrose and 6 g safflower oil/d. CM administration showed significantly greater effects to improve muscular endurance, isokinetic knee extension strength, fat free mass and to reduce fat mass compared to placebo. Furthermore the supplement group had an increase in serum creatinine but not creatinine clearance suggesting no negative effect on renal function.

You’ll Feel Better: Not only will you find yourself with more energy and confidence, less stress and anxiety, and a better overall mood, but you’ll actually begin to think better (resistance training has been proven to help increase cognitive function). And while training too close to bedtime can be a bad idea, exercising earlier in the day has been proven to help prevent sleep apnea and insomnia. I even improved my posture – when I started lifting, I was 5’4”.  Now I’m 5’5.5”.
These terms combine the prefix iso- (meaning "same") with tonic ("strength") and plio- ("more") with metric ("distance"). In "isotonic" exercises the force applied to the muscle does not change (while the length of the muscle decreases or increases) while in "plyometric" exercises the length of the muscle stretches and contracts rapidly to increase the power output of a muscle.

Do standard squats with a weighted bar. Place enough weight on a bar and rack so that it's a little lower than shoulder height. It should be heavy enough that doing a squat is difficult, but not impossible. If you're a beginner, this may mean using a bar without any weight to start with. Duck under the bar and stand up so that the bar rests comfortably on your trapezius muscles, just below the neck. Keep your knees slightly bent and your legs slightly wider than shoulder width. Lift the bar up off the rack and move backwards one step.
Creatine is a powerful supplement for strength and muscle gain. It always recommended utilize creatine before the workout. It gives you the strength and power of more repetition. With creatine, you can also use SR-9009. SR-9009 has the capabilities of lowering obesity and reversing metabolic syndrome. SR-9009 allows to perform more cardio training, weight loss, improve cholesterol levels, and gain lean muscle mass. Hope this information will help someone.
How much of a difference does EPOC make? Well, in one research study of young women, basal metabolic rate spiked by 4.2 percent 16 hours following a strength-training session that lasted an hour and 40 minutes—the equivalent of burning an extra 60 calories, on average. That’s a long workout, and 60 extra calories isn’t exactly huge. Plus, EPOC is not a permanent boost. Research suggests it may last anywhere from 12 hours to a few days, depending on the workout and who is doing it. The calories you burn through EPOC can add up over time, especially if you’re lifting weights three or four times a week, but all in all, it doesn’t have a very big effect on your metabolism.
Creatine is most commonly found in the basic form of creatine monohydrate, which is the standard form and usually recommended due to the low price. It can also be micronized to improve water solubility, or the monohydrate can be temporarily removed to concentrate creatine in a small volume supplement. Neither alteration changes the properties of creatine.
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When it comes to building lean muscle, size bodybuilders are king. That’s their ultimate goal. Sure, Crossfit, powerlifting and all the other modalities will build muscle, but that’s not their focus. They want performance and any muscle they build is a side effect. Not so with bodybuilding where muscle size and shape are the priorities. Learning how to build muscle for the sake of building muscle has some benefits to the performance athlete. It allows for ais less injury prone. Its also a fact that bigger muscle contract harder regardless of technique or form, so it’s a good strategy to throw in some bodybuilder muscle building sessions here and there to give yourself stronger muscles to then train for performance. Build the muscle bigger, then train it to perform better.
Maintaining proper form is one of the many steps in order to perfectly perform a certain technique. Correct form in weight training improves strength, muscle tone, and maintaining a healthy weight. Proper form will prevent any strains or fractures.[6] When the exercise becomes difficult towards the end of a set, there is a temptation to cheat, i.e., to use poor form to recruit other muscle groups to assist the effort. Avoid heavy weight and keep the number of repetitions to a minimum. This may shift the effort to weaker muscles that cannot handle the weight. For example, the squat and the deadlift are used to exercise the largest muscles in the body—the leg and buttock muscles—so they require substantial weight. Beginners are tempted to round their back while performing these exercises. The relaxation of the spinal erectors which allows the lower back to round can cause shearing in the vertebrae of the lumbar spine, potentially damaging the spinal discs.
Squats target both your inner and outer thighs. Use a barbell heavy enough to challenge your muscles but light enough that you can still control your form. Hold it behind your head with your feet shoulder-width apart. Tighten your core, then squat down as far as comfortable. There should be no knee or back pain. As you come back up, raise your hips and chest together.

However, the basis of “take creatine after your workout” comes from a 2013 study published in the JISSN, which can be found here (open access too!). In this study, recreational male bodybuilders (19 men overall) were given five grams of creatine either before or after their workouts. They trained five days per week but were also directed to consume 5g on their rest days at any time they wanted. The workouts were fairly similar to most gym workouts, and the methodology (what they did and how they did it) suggests that the findings would apply to most weightlifters.
At the end of the day, yes, strength training does impact your metabolism, but any boost you get will be minimal and completely secondary to all of the other health benefits of strength training. Any change in metabolism or increase in calorie burn will vary widely from person to person, and depends on so many factors: your genetics, eating habits, health conditions, what workout you do that day, how much sleep you’re getting, and even how stressed you are on any given day. But incorporating a couple of strength training sessions into your fitness routine is worth doing no matter what—you’ll feel yourself get stronger, and put yourself in a position to say healthier throughout life. Those are the best, most promising benefits to work for.
Cyclocreatine (1-carboxymethyl-2-iminoimidazolidine) is a synthetic analogue of creatine in a cyclic form. It serves as a substrate for the creatine kinase enzyme system, acting as a creatine mimetic. Cyclocreatine may compete with creatine in the CK enzyme system to transfer phosphate groups to ADP, as coincubation of both can reduce cyclocreatine’s anti-motility effects on some cancer cells.[96]
Bodybuilding developed in the late 19th century, promoted in England by German Eugen Sandow, now considered as the "Father of Bodybuilding". He allowed audiences to enjoy viewing his physique in "muscle display performances". Although audiences were thrilled to see a well-developed physique, the men simply displayed their bodies as part of strength demonstrations or wrestling matches. Sandow had a stage show built around these displays through his manager, Florenz Ziegfeld. The Oscar-winning 1936 musical film The Great Ziegfeld depicts the beginning of modern bodybuilding, when Sandow began to display his body for carnivals.
Researchers described the study as one of the first to examine how strength training can reduce the risk of cardiovascular disease, separate from the effects of aerobic activity like running or long walks. The point: for those who are not meeting recommended guidelines for aerobic activity—perhaps because they lack the time—bursts of weight training can be enough.
In the stomach, creatine can degrade by about 13% due to the digestive hormone pepsin, as assessed by simulated digestion.[127] Although creatinine is a known byproduct of creatine degradation, simulated gastric digestion did not increase creatinine levels, indicating that other breakdown products were formed. However, creatinine was noted to increase in the presence of pancreatin, a mixture of pancreatic enzymes.[127] 
Isometric exercise provides a maximum amount of resistance based on the force output of the muscle, or muscles pitted against one another. This maximum force maximally strengthens the muscles over all of the joint angles at which the isometric exercise occurs. By comparison, weight training also strengthens the muscle throughout the range of motion the joint is trained in, but only maximally at one angle, causing a lesser increase in physical strength at other angles from the initial through terminating joint angle as compared with isometric exercise. In addition, the risk of injury from weights used in weight training is greater than with isometric exercise (no weights), and the risk of asymmetric training is also greater than with isometric exercise of identical opposing muscles.
A retrospective study [81], that examined the effects of long lasting (0.8 to 4 years) CM supplementation on health markers and prescribed training benefits, suggested that there is no negative health effects (including muscle cramp or injuries) caused by long term CM consumption. In addition, despite many anecdotal claims, it appears that creatine supplementation would have positive influences on muscle cramps and dehydration [82]. Creatine was found to increase total body water possibly by decreasing the risk of dehydration, reducing sweat rate, lowering core body temperature and exercising heart rate. Furthermore, creatine supplementation does not increase symptoms nor negatively affect hydration or thermoregulation status of athletes exercising in the heat [83,84]. Additionally, CM ingestion has been shown to reduce the rate of perceived exertion when training in the heat [85].
By increasing the overall pool of cellular phosphocreatine, creatine supplementation can accelerate the reycling of ADP into ATP. Since ATP stores are rapidly depleted during intense muscular effort, one of the major benefits of creatine supplementation is its ability to regenerate ATP stores faster, which can promote increased strength and power output. Over 95% of creatine is stored in muscle at a maximum cellular concentration of 30uM. Creatine storage capacity is limited, though it increases as muscle mass increases.[24] A 70 kg male with an average physique is assumed to have total creatine stores of approximately 120g.[25] The body can store a lot more energy as glycogen in the liver, brain, and muscles,[26][27] and even more as fat.
Citrulline Malate is an amino acid also known as L-Citrulline and is taken for many different medical conditions. There is some research that shows that the amino acid may help improve performance while exercising by reducing fatigue. What does that mean for you? In your muscle building efforts, you can use this supplement to help you make it through longer, harder workouts. This will spur more muscle building in response to the trauma your muscles experience in a tough workout. Not only that, but Citrulline Malate can also help reduce soreness after a workout. Who doesn’t want to avoid feeling sore? Reduced soreness means you can get back to the gym the next day with renewed enthusiasm.

Back in the 1970s, scientists discovered that taking creatine in supplement form might enhance physical performance. In the 1990s, athletes started to catch on, and creatine became a popular sports supplement. The supplement is particularly popular among high school, college, and professional athletes, especially football and hockey players, wrestlers, and gymnasts. 

^ Jump up to: a b c d e f g h Momaya A, Fawal M, Estes R (April 2015). "Performance-enhancing substances in sports: a review of the literature". Sports Med. 45 (4): 517–531. doi:10.1007/s40279-015-0308-9. PMID 25663250. Wilson et al. [91] demonstrated that when non-resistance trained males received HMB pre-exercise, the rise of lactate dehydrogenase (LDH) levels reduced, and HMB tended to decrease soreness. Knitter et al. [92] showed a decrease in LDH and creatine phosphokinase (CPK), a byproduct of muscle breakdown, by HMB after a prolonged run. ... The utility of HMB does seem to be affected by timing of intake prior to workouts and dosage [97].