How to use oral anabolic steroids

If want your oral steroids to work well, you should know which factors influence oral bioavailability or oral drug absorption.

There are many factors affecting drug absorption, physicochemical characteristics, physiological properties, formulation and food effects. Other factors, such as the user’s conditions, age, metabolism enzymes, administration time, drug interaction, and so on, are also affecting the pharmacokinetics in drug absorption. These factors will change the relationship between drug intake and clinical response.

A relevant study on the absorption of Metformin, showed that physiological properties affecting drug absorption are altered gastric emptying and gastrointestinal motility. Results showed that AUC (0,infinity) and UR% (percent dose excreted unchanged in urine) generally increased with increase in gastric emptying time and small intestinal transit times, that is the extent of metformin absorption is improved when the gastrointestinal motility is slowed.

Food Effect

Steroid hormones, even when they don't have esters, are still considered lipid- (fat) soluble compounds. They basically like to dissolve in fat more than they do water. If you take a fat-soluble hormone with a meal, particularly one with a high fat content, some of the steroid is going to get dissolved with the fat in your stomach. This is, again, a natural property of the steroid. Some of the fat you ate may go undigested, which will ultimately reduce the overall bioavailability of the steroid hormone by preventing some of it from being absorbed from the gastrointestinal tract (and transported to body tissues).

I looked for a long time for some reference to this and finally found mention of a study that took place several decades ago with stanozolol. The experiment administered an equal amount of hormone to two groups of animals. One group received the drug mixed with their food, and in the other, it was administered directly into the animals' stomachs via a feeding tube (on an empty stomach). The drug indeed had a considerably stronger effect on promoting nitrogen retention (a measure of protein synthesis) when it was given on an empty stomach. Seems like very strong support for this position.

So taking your pills on an empty stomach does seem best- at least when it comes to the standard c17-alpha-alkylated (most) oral steroids. If you want to be really meticulous, you can also take your pills with a glass of water, which will help their absorption a little by facilitating the breakdown of tablets and binders and aiding in the transport of the hormone. Chewing the pills before swallowing will also help, again through rapid breakdown and transport to the GI tract. Also, exercising soon after taking your pills draws blood away from your stomach, which could slow or lower drug absorption. Try not to train right after taking them if you can.

The pH differences in the contents of the upper GI tract between fed and fasted states can influence the dissolution and absorption of weakly acidic and basic drugs. Elevation of gastric pH following a meal may enhance the dissolution of a weak acid in the stomach but inhibit that of a weak base. Furthermore, food inhibits the rate of gastric emptying, prolonged retention in the stomach may increase the proportion of drug that dissolves prior to passage into the small intestine, which is the primary site of drug absorption.

Of course, the advice of taking your pills on an empty stomach wouldn't apply to those oral steroids that rely on lymphatic transport, or absorption of the drug by the lymphatic system (with dietary fat) to bypass the liver. Lymphatic delivery is occasionally used with unprotected (non-c17-alpha-alkylated) steroid hormones, although this isn't a common method of steroid delivery. It won't be of relevance with most pills and the only drug really like that now is Andriol (testosterone undecanoate). At one time, however, other lymphatically transported agents such as Maxibolin (ethylestrenol) and Anabolicum Vister (quinbolone) also circulated on the black market. Bodily utilization of drugs like these may actually be aided by consuming them with a high-fat meal.

Old Ciba research also showed that an increased metabolism (by example from using T3, increases excretion and thus decreases its bioavailability/absorption).

If you are taking Oral Steroids, remember to always drink a full glass of water with it. Drinking water helps the tablet dissolve quicker and also prevents stomach irritation. The pills contain a compound called c17 methyl, which helps the steroid from being destroyed in the stomach and liver so it can work on muscle growth. However, the downside to c17 methyl is that it irritates the stomach and is toxic to the liver. Drinking lots of water with the pills will help lessen the impact of c17 methyl on your body.

Liver toxity exaggerated

It’s said that oral steroids ruin your liver, that’s highly exaggerated, I posted on it here.

It seems that weekly we hear about some professional athlete who sullies himself and his sport through abuse of steroids. The melodrama unfolds, careers and statistics are brought low and asterisked, and everyone bemoans another fallen competitor.  Yet there are millions of cases of steroid use that occur daily with barely a second thought:  Millions of women take birth control pills, blithely unaware that their effects may be subtly seeping into and modulating brain structure and activity.  But surprisingly anabolic steroids are illegal and the birth control pill is not.

Effect of caffeine dosing

Information obtained as a result of law enforcement activities in Portugal, has indicated that a particular group of athletes was using caffeine in conjunction with oxandrolone. As a result scientists investigated the possible effect of this co-administration.

Caffeine was included as a doping agent by the IOC in 1984. Initially a cut-off of 15 μg/mL was established and this value was lowered to 12 μg/mL in 1985. In 2004 the World Anti-Doping Agency (WADA) did not include caffeine on the list of prohibited substances.

Although some performance-enhancing effects of caffeine as stimulant and diuretic have been well described, it is problematic to control abuse of caffeine and to distinguish from normal dietary intake.

Oxandrolone (Anavar or Var) has been described as enhancing protein synthesis and lean muscle mass, advantageous effects which would prompt athletes to abuse it. This synthetic 2-oxasteroid derived from testosterone was first prepared in 1962. It showed a very strong anabolic effect, yet apparently with much lower androgenic activity, thereby significantly reducing virilization effects.

The excretion profiles of oxandrolone and epioxandrolone, with and without caffeine dosing, are shown in Figure 1. For oxandrolone the maximum excretion rate is 10ng/min undosed; with the caffeine that rate increases to 150 ng/min. Similarly, for epioxandrolone the maximum undosed rate is 0.9 ng/min and 19 ng/min dosed. The maximal rates occur at less than 4 h undosed, less than 6 h for the dosed study. The oxandrolone excretion data plotted together with the caffeine data are shown in Figure 2. The same data for epioxandrolone are in Figure 3. The caffeine excretion shows a maximum concentration of ~18 μg/mL at 4.7 h (Fig. 4).

In comparing the data from the two studies it seems clear that caffeine does, in fact, alter the excretion profile of oxandrolone. With the 300 mg of caffeine, there were very large increases in excretion amount and rate observed for both oxandrolone and epioxandrolone. Overall the total amount excreted for these two steroids is about 20 times higher compared to the administration of oxandrolone alone (with dietary intake of caffeine). There was however a differential in the increases: total oxandrolone increased more than 20-fold, while total epioxandrolone increased only about 15-fold. It also appears that the patterns of oxandrolone and epioxandrolone excretion follows the caffeine excretion pattern.

There are studies which report that caffeine accelerates absorption and bioavailability of some drugs (e.g., paracetamol). To better understand if there is an additional metabolic effect, alternative routes of administration with/without simultaneous caffeine dosing should be tested; in addition blood samples should be taken. For these studies it would be advisable to test other anabolic steroids.

One final observation. With the 300 mg of caffeine there is only one sample in which the concentration rises above the former 12 μg/mL threshold.

Synergism

R esearchers from the University of California took a group of 22 HIV patients, eleven HIV patients were given a weekly injection of 100 mg testosterone enanthate and took a placebo. The other eleven men were given 20 mg oxandrolone extra each day. The men did 1 hour of weight training 3 times a week. The oxandrolone group had gained almost 8 kg fat free mass after 8 weeks, they also lost a few ounces more fat than the men in the placebo group. The researchers concluded that it's not necessary to do a 20-week course of 600 mg to gain 8 kg fat free mass. It's possible to achieve the same results with much lower doses.

Aside from receptor interaction/activation, it is well known that an effect of steroids on muscle growth is also through its ability to activate and affect the secretion and release of other muscle growth promoting hormones (such as IGF-1 and MGF) that hold an equally effective influence on muscle growth[3], which might interact with other difference receptor types within muscle tissue. This creates a synergistic effect between the anabolic steroid and the other auxiliary hormones involved and interconnected in muscle growth. Evidence of this can be seen in various anabolic steroids that in fact do not exhibit very significant binding strength to the androgen receptor, such as Dianabol (Methandrostenolone) where its effects lie in non-receptor mediated effects as evidenced by a particular study utilizing high doses of the compound that demonstrated a high level of nitrogen retention in the muscles promoted by Dianabol.

Anadrol (Oxymetholone) is another such anabolic steroid that exhibits poor androgen receptor binding strength but is known to be a very strong anabolic agent.

Anadrol is a derivative of DHT. Derivatives of DHT should normally exhibit no estrogenic effects on the body by virtue of the fact that they cannot convert (aromatize) into Estrogen. Although Anadrol too cannot aromatize, the current hypothesis is that it (or its metabolites) seems to act as an Estrogen itself in various tissues of the body. This is a perfect example of how various anabolic steroids will exhibit different effects than others, and perhaps some will exhibit unpredictable effects in comparison to others.

Oral vs Injectable Stanozolol

ME Olson - ‎2000: The objective of the study was to determine the influence of either oral or intramuscular administration of stanozolol on nitrogen retention in dogs

Both oral and injectable stanozolol resulted in significant increases in amino acid nitrogen retention compared to pretreatment values. Oral stanozolol increased nitrogen retention from 29.2 to 50.3, while stanozolol injection increased nitrogen retention from 26.6 to 67.0. The response to intramuscular administration was significantly greater than the response to the oral dosing regime. Stanozolol increases amino acid nitrogen retention in dogs, as has been previously observed in rats. This action of stanozolol may be beneficial in dogs under stress of surgical trauma and chronic disease. Stanozolol, commonly known as Winstrol®, is primarily to improve appetite and increase strength and overall vitality in ailing animals like dogs .

Studies have shown that taking an oral anabolic steroid with food may decrease its bioavailability. This is caused by the fat-soluble nature of steroid hormones, which can allow some of the drug to dissolve with undigested dietary fat, reducing its absorption from the gastrointestinal tract. First it’s not known if the dogs received the stanozolol in a fasted state. And second, as carnivores or meat eaters, dogs have evolved with a naturally short bowel. This makes it unsuitable to extrapolate results on sled dogs to human bodybuilders, even though you can find this all over the net.

6′,7′-Dihydroxybergamottin (DHB) is a natural furanocoumarin found mostly in grapefruit juice and Seville orange juice. DHB is believed to be responsible for so-called grapefruit juice effect.

Why is 6′,7′-Dihydroxybergamottin Found in Supplements?

6′,7′-Dihydroxybergamottin is sold as “anabolic amplifier” and is supposed to increase the absorption of supplements, drugs, oral anabolic steroids and even food. DHB was reported to be very effective at inhibiting the cytochrome P450 CYP3A4 enzyme activity in intestine and liver, which is responsible for decreasing small foreign organic molecule absorption.

Active ingredients (such as 6′,7′-DHB) in grapefruit juice are responsible for greater bioavailability of drugs after oral dosing but not after intravenous administration of the same drugs. It has been shown that 6-beta-hydroxylase activity (exhibited by CYP3A4 enzyme) plays an important role in metabolism of the anabolic steroids. Both in vivo and vitro hydroxylation at 6-beta-position catalyzed by CYP3A4 enzyme was reported for testosterone, progesterone, cortisol and androstenedione, as well as for the synthetic compounds, Dianabol (methandrostenolone or metandienone), budesonide and dexamethasone. Therefore, many bodybuilders couple their oral anabolics with 6′,7′-DHB and/or bergamottin. In this case, with greater bioavailability comes greater toxicity and adverse reactions (most commonly gynecomastia, high blood pressure, acne and male pattern baldness).

In 2014 Karen M. VanderMolen et al. analyzed six sports nutrition supplements that were labeled to contain the furanocoumarin(s) bergamottin and/or 6′,7′-dihydroxybergamottin. Contrary to the product labeling, four of the supplements contained no detectable quantities of either furanocoumarin, while two of the supplements contained minimal amounts. CYP3A inhibition by this low amounts of bergamottin and DHB was greater than it could be accounted for by the two furanocoumarins which suggests the presence of other potent or highly abundant CYP3A inhibitors.

What is Grapefruit Juice Effect and is 6′,7′-Dihydroxybergamottin Responsible for it?

Grapefruit juice can increase the oral bioavailability of a broad range of medications as it produces mechanism-based inhibition of intestinal drug metabolism when consumed. As mentioned before 6′,7′-dihydroxybergamottin has been identified as probable active constituent responsible for grapefruit juice effect. However, studies report that it is not the major active ingredient, although it largely contributes to the grapefruit juice-felodipine interaction. A study published on Nature.com concluded that grapefruit juice (but not 6′,7′-DHB) increased concentration of cyclosporine probably because intestinal P-glycoprotein may be a more important determinant of cyclosporine availability than inhibition of cytochrome P450 CYP3A4. Studies suggest that grapefruit juice also affects, but only to a minor extent, the modulation of P-glycoprotein function. 6′,7′-Dihydroxybergamottin is an important contributor to grapefruit juice effect, however grapefruit juice contains many other flavonoids and furanocoumarin derivatives that may alter the metabolism of drugs by CYP.

Side Effects and Precautions

Inhibition of the CYP3A4 in the small intestine may elevate drug plasma concentrations (especially felodipine, amiodarone) which increases the risk of adverse reactions (increases the toxicity) of administered drugs [14]. So, 6′,7′-dihydroxybergamottin does not cause side effects per se but it can interfere with prescription medications which may trigger dangerous side effects.