Dr. Darryn Willoughby, a professor of health, human performance and recreation and the director of the Exercise and Biochemical Nutrition Laboratory at Baylor University, told us that even in studies where there was an increase in testosterone, it was only around 15–20 percent. “In men with clinically normal testosterone levels, this modest increase will most likely not be anabolic enough to improve exercise performance,” he says. So if you have normal testosterone levels, and are simply trying to get an extra edge in gaining muscle, losing weight, or some extra time in the bedroom — you might see some results from taking a testosterone booster. But really, these will be most useful for men with low testosterone trying to get back to a healthy testosterone range.

That there is an association between depression and testosterone concentration seems possible because of the observation that depression may be associated with reduced testosterone concentrations, hypogonadal men may have their symptoms of depression relieved by TRT and that testosterone itself may have anti-depressant properties (Pope et al 2003). The evidence, however, is inconsistent. Seidman and colleagues (2002), for example, found that there was no relationship between testosterone and depression but there was an association of testosterone with dysthymia. McIntyre and colleagues (2006), on the other hand, found that middle-aged men with depression did have a reduction in bio-available testosterone.

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The use of anabolic steroids (manufactured androgenic hormones) shuts down the release of luteinising hormone and follicle stimulating hormone secretion from the pituitary gland, which in turn decreases the amount of testosterone and sperm produced within the testes. In men, prolonged exposure to anabolic steroids results in infertility, a decreased sex drive, shrinking of the testes and breast development. Liver damage may result from its prolonged attempts to detoxify the anabolic steroids. Behavioural changes (such as increased irritability) may also be observed. Undesirable reactions also occur in women who take anabolic steroids regularly, as a high concentration of testosterone, either natural or manufactured, can cause masculinisation (virilisation) of women.

Vitamin D deficiency is a growing epidemic in the US, and is profoundly affecting men’s health. The cholesterol-derived steroid hormone vitamin D is crucial for men’s health. It plays a role in the development of the sperm cell nucleus, and helps maintain semen quality and sperm count. Vitamin D can also increase your testosterone level, helping improve your libido. Have your vitamin D levels tested using a 25(OH)D or a 25-hydroxyvitamin D test. The optimal level of vitamin D is around 50 to 70 ng/ml for adults. There are three effective sources of vitamin D:
Afrisham, R., Sadejh-Nejadi, S., SoliemaniFar, O., Kooti, W., Ashtary-Larky, D., Alamiri, F., … Khaneh-Keshi, A. (2016, November 24). Salivary testosterone levels under psychological stress and its relationship with rumination and five personality traits in medical students. Psychiatry Investigations, 13(6), 637–643. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5128352/
Testosterone boosters are used by many athletes worldwide to achieve a significant muscle mass increase within a short period of time.[1] However; one cannot be completely confident in terms of the quality and efficacy of such products because of several reasons, such as the possibility of bad storage conditions and originating from an unreliable source. Over the years, some consumers of testosterone boosters have complained of kidney and liver abnormalities that could be linked to their use of boosters.[10] Cases of erroneous product administration have occurred in the past as athletes may not follow the instructions on the label fully, which can lead to many side effects.[11] In the present case, a man was admitted to a hospital because of a severe abdominal pain. The pain was later found to be caused by liver injury. The diagnosis confirmed that the levels of the key hepatic enzymes were markedly elevated. The medical complications observed were found to have occurred following the consumption of two courses of a commercial testosterone booster. According to researchers based in the US, about 13% of the annual cases of acute liver failure are attributable to idiosyncratic drug- and/or supplement-induced liver injury.[12] Marked increase in the levels of ALT, AST, and gamma-glutamyl transferase was observed after consuming the first course of the commercial testosterone booster, and they started to decline after the 2nd and 3rd course. This abruptly increases the levels of liver enzymes after the first course may be attributed to the interruption effect of commercial testosterone booster on liver function as a result of the effects of its ingredients.
Beast Sports Nutrition - Super Test has all four of our dream ingredients: magnesium, fenugreek, longjack, and zinc. These ingredients have all been demonstrated to help increase natural testosterone levels, with plenty of scientific research to support them (done on humans too, and not just rats). By combining all four ingredients, Super Test has the best chance of helping to increase your testosterone levels, and thereby helping you gain muscle or have a more active sex life.
Exercise is one of the most effective ways to prevent many lifestyle-related diseases. Interestingly, it can also boost your testosterone. A large review study found that people who exercised regularly had higher testosterone levels. In the elderly, exercise increases testosterone levels, fitness and reaction time. New research in obese men suggests that increased physical activity was even more beneficial than a weight loss diet for increasing testosterone levels. Resistance training, such as weight lifting, is the best type of exercise to boost testosterone in both the short- and long-term. High-intensity interval training (HIIT) can also be very effective, although all types of exercise should work to some extent. Taking caffeine and creatine monohydrate as supplements may further boost your levels when combined with a training program.

It seems that adequate testosterone levels are an important influence on sexual symptoms in the aging male and also influence the response of men to PDE-5 inhibitors, the first line treatment for erectile dysfunction in men. Many would now suggest screening for testosterone deficiency in all men presenting with erectile dysfunction (Gore and Rajfer 2004; Shabsigh 2005). This would seem appropriate because, in addition to benefits on sexual function, identification and treatment of hypogonadal men with testosterone could improve other symptoms of hypogonadism and protect against other conditions such as osteoporosis.


However, along with bone healthy and density, vitamin D may also ensure proper testosterone production in men. Studies suggest a correlation between low testosterone levels and vitamin D deficiencies. Other research suggests that men supplementing with vitamin D experienced a statistically significant increase in testosterone levels. Studies found that simply spending more time in the summer sun increased the subjects’ vitamin D and testosterone levels.
DHEA (dehydroepiandrosterone) extract - this is a chemical that used in your body which a ‘hormone precursor’. This means it’s the chemical used by the body to create hormones like oestrogen or testosterone. When taken as supplement it is believed to boost testosterone levels, but DHEA has not been shown to increase testosterone in men. DHEA comes in two form:
D-Aspartic acid is a natural amino acid involved in the synthesis and release of testosterone, which research shows can be used as a testosterone booster for infertile men. One 90-day study gave D-Aspartic acid to men with impaired sperm production, and found their sperm count rose from 8.2 million sperm per ml to 16.5 million sperm per ml, more than a 100 per cent increase.
Does zinc provide testosterone benefits? The answer is, yes. It is an essential mineral which is used in many processes within the body and has a similar role like vitamin D. Men who have a deficiency of zinc may suffer from low testosterone levels but taking zinc supplements can help them to improve the testosterone levels. Zinc deficiency is an essential factor in infertility because it also reduces the sperm count, but with supplements, the sperm count increases along with improvement in testosterone levels. It also helps to recover from high-intensity interval training because that also cause the decline in testosterone levels.
It may be unlikely to completely eliminate products with EDCs, but there are a number of practical strategies that you can try to limit your exposure to these gender-bending substances. The first step would be to stop using Teflon cookware, as EDCs can leach out from contaminated cookware. Replace them with ceramic ones. Stop eating out of cans, as the sealant used for the can liner is almost always made from powerful endocrine-disrupting petrochemicals known as bisphenols, e.g. Bisphenol A,
Increase testosterone if you’re an adult with abnormally low levels. Under most circumstances, adults who have been medically diagnosed with low testosterone levels can safely increase their levels, and natural methods can be some of the healthiest ways to do so. That being said, you should avoid intentionally increasing your testosterone if you are still an adolescent or if you’re an adult with normal or undiagnosed levels.
Findings that improvements in serum glucose, serum insulin, insulin resistance or glycemic control, in men treated with testosterone are accompanied by reduced measures of central obesity, are in line with other studies showing a specific effect of testosterone in reducing central or visceral obesity (Rebuffe-Scrive et al 1991; Marin, Holmang et al 1992). Furthermore, studies that have shown neutral effects of testosterone on glucose metabolism have not measured (Corrales et al 2004), or shown neutral effects (Lee et al 2005) (Tripathy et al 1998; Bhasin et al 2005) on central obesity. Given the known association of visceral obesity with insulin resistance, it is possible that testosterone treatment of hypogonadal men acts to improve insulin resistance and diabetes through an effect in reducing central obesity. This effect can be explained by the action of testosterone in inhibiting lipoprotein lipase and thereby reducing triglyceride uptake into adipocytes (Sorva et al 1988), an action which seems to occur preferentially in visceral fat (Marin et al 1995; Marin et al 1996). Visceral fat is thought to be more responsive to hormonal changes due to a greater concentration of androgen receptors and increased vascularity compared with subcutaneous fat (Bjorntorp 1996). Further explanation of the links between hypogonadism and obesity is offered by the hypogonadal-obesity-adipocytokine cycle hypothesis (see Figure 1). In this model, increases in body fat lead to increases in aromatase levels, in addition to insulin resistance, adverse lipid profiles and increased leptin levels. Increased action of aromatase in metabolizing testosterone to estrogen, reduces testosterone levels which induces further accumulation of visceral fat. Higher leptin levels and possibly other factors, act at the pituitary to suppress gonadotrophin release and exacerbate hypogonadism (Cohen 1999; Kapoor et al 2005). Leptin has also been shown to reduce testosterone secretion from rodent testes in vitro (Tena-Sempere et al 1999). A full review of the relationship between testosterone, insulin resistance and diabetes can be found elsewhere (Kapoor et al 2005; Jones 2007).
Ten healthy men aged around 24 years old spent 1 week sleeping for 8 hours per night at home, they then spent the next 11 nights in a lab. They slept for 10 hours per night for 3 nights, followed by 8 nights of restricted sleep, when they slept for only 5 hours. Doctors checked their blood every 15 to 30 minutes during the last night that they slept 10 hours, as well as on the sleep-restricted session.
At the present time, it is suggested that androgen replacement should take the form of natural testosterone. Some of the effects of testosterone are mediated after conversion to estrogen or dihydrotestosterone by the enzymes aromatase and 5a-reductase enzymes respectively. Other effects occur independently of the traditional action of testosterone via the classical androgen receptor- for example, its action as a vasodilator via a cell membrane action as described previously. It is therefore important that the androgen used to treat hypogonadism is amenable to the action of these metabolizing enzymes and can also mediate the non-androgen receptor actions of testosterone. Use of natural testosterone ensures this and reduces the chance of non-testosterone mediated adverse effects. There are now a number of testosterone preparations which can meet these recommendations and the main factor in deciding between them is patient choice.
Instead of turning to some drug that can only ameliorate symptoms and cause additional complications, I recommend using a natural saw palmetto supplement. Dr. Moerck says that there are about 100 clinical studies on the benefits of saw palmetto, one of them being a contributed to decreased prostate cancer risk. When choosing a saw palmetto supplement, you should be wary of the brand, as there are those that use an inactive form of the plant.
12)  Use Aswaghanda and Collagen Protein:  This adaptogenic herb has been shown to reduce stress hormone, increase DHEA and boost testosterone levels.  You can take the Cortisol Defense to help you get restorative sleep at night which will support your testosterone.  In addition, I personally enjoy using the Organic Bone Broth Collagen in addition to the Amino Strong for a post weight training shake.  This protein powder has all the benefits of collagen protein and it has 500 mg of high potency ashwagandha in each serving!
We do note that Beast Sports’ supplemental magnesium level is fairly low — 26 mg per serving, up to 52 mg per day. If your diet is not particularly rich in magnesium (found in leafy greens, nuts, and whole grains), Beast Sports may not give you enough to meet the daily recommended dose. However, if you’re taking other multi-vitamins or supplements with magnesium, you’re less likely to cross that 350mg daily upper limit.
Starting around the age of 30, men’s testosterone production begins to decline and only continues to go down as you get older. Whether you simply want to build lean muscle or ensure that you always have healthy levels of testosterone, there are a wide range of dietary supplements that can help to increase your testosterone levels. Let’s take a look at some of the most popular ingredients to boost your testosterone. 
For example, the study published in Obesity Research tells that the scientists measured testosterone levels in two groups of middle-aged men with obesity. One group underwent a 16-week weight loss program, while the second group did nothing. Each participant of the first group lost 20 kg on the average. And these participants experienced a significant increase in testosterone levels. So, the fight against overweight is very important for those who want to overcome testosterone deficiency. But starvation is strictly forbidden because this is a stressful situation which leads to the sharp decline in T levels.

Lean beef, chicken, fish, and eggs are some of your options. Tofu, nuts, and seeds have protein, too. Try to get about 5 to 6 ounces per day, although the ideal amount for you depends on your age, sex, and how active you are. When you don't eat enough of these foods, your body makes more of a substance that binds with testosterone, leaving you with less T available to do its job.


Testosterone has several positive effects on sexual function, but its most significant effect is on libido, sexual interest and arousal. Boys going through puberty develop an enhanced interest in sex (thoughts, fantasies, masturbation, intercourse) as a consequence of rising levels of testosterone. Hypogonadal men usually have a significant improvement in libido when TRT is initiated (Wang et al 2000; Morley and Perry 2003).
Interest in testosterone began when farmers of old first noticed that castrated animals were more docile than their intact peers. Ditto for castrated humans. For human males with intact gonads, testosterone increases during puberty. It deepens the voice, increases muscle growth, promotes facial and body hair, and spurs the sex drive. Testosterone also is associated with personality traits related to power and dominance.

Individuals with metabolic syndrome are at increased risk for developing coronary artery disease and diabetes mellitus. Predicting who might develop the metabolic syndrome would allow preventive measures to be taken in addition to weight control and other lifestyle modifications such as cessation of smoking and increased exercise. It is known that with decreasing testosterone availability in aging males there is an increase in fat mass and decrease in lean body mass (van den Beld et al 2000), there are disorders of insulin and glucose metabolism (Haffner et al 1996) and dyslipidemia (Tsai et al 2004). Kupelian and colleagues (2006) in analyzing data from the Massachusetts Male Aging Study demonstrated that men with low levels of testosterone, sex hormone-binding globulin, or clinical androgen deficiency, especially men with a BMI of greater than 25, were at increased risk of developing the metabolic syndrome and hence, diabetes mellitus and/or coronary artery disease.

Dr. Anthony’s Notes: Here's a funny little effect – fenugreek can make you sweet and your urine smell sweet like Maple Syrup. Hell, this could be a good thing for you! This supplement is commonly used for good reasons – it's quite effective for enhancing libido when stacked with the other herbs on this list. Medical Note: Fenugreek may interact with blood thinning medications (Warfarin, Coumadin, Xarleto). Check with your doctor before taking any of these supplements. How To Take Fenugreek: Take 400-600mg (capsule) with food; it's best to take a product standardized for fenuside.
The diagnosis of late-onset hypogonadism requires the combination of low serum testosterone levels with symptoms of hypogonadism. Questionnaires are available which check for the symptoms of hypogonadism. These have been validated for the assessment of aging patients with hypogonadism (Morley et al 2000; Moore et al 2004) but have a low specificity. In view of the overlap in symptoms between hypogonadism, aging and other medical conditions it is wise to use a formal method of symptom assessment which can be used to monitor the effects of testosterone replacement.
But when a premenopausal woman’s testosterone levels are too high, it can lead to polycystic ovary syndrome (PCOS), a condition that increases the risk of irregular or absent menstrual cycles, infertility, excess hair growth, skin problems, and miscarriage. High levels of testosterone in women, whether caused by PCOS or by another condition, can cause serious health conditions such as insulin resistance, diabetes, high cholesterol, high blood pressure, and heart disease. (12)
Testosterone retains nitrogen and is an essential ingredient in the development and maintenance of muscle mass (Sinha-Hikim et al 2006). With a diminution in testosterone, muscle mass diminishes as does strength. Weakness and fatigue result. A number of studies have demonstrated the ability of testosterone to restore lean body mass (muscle) in hypogonadal men, while at the same time causing a reduction in fat mass (Wang et al 2004). Treatment of hypogonadal men with testosterone results in improvement in overall physical performance as well as strength as assessed by, eg, hand grip power (Page 2005). Because of decreased muscle strength and impaired balance, older hypogonadal men are susceptible to falling and since they may already be osteopenic or osteoporotic as a consequence of hypogonadism, they are at increased risk for fracture as a result of the fall (Szulc et al 2003). Men with low levels of testosterone as in androgen deprivation therapy for prostate cancer, have a significant decrease in lean body mass and hemoglobin, while at the same time they experience an increase in weight, body fat and body mass index (Smith et al 2002). Treatment of frail hypogonadal men with testosterone, therefore, can result in changes in muscle gene expression, increased muscle mass, improvements in strength, power and endurance and improved physical function.

Interestingly, the Belgian company Solvay, acquired for €4.5 billion in 2010 by American pharmaceutical giant Abbott, didn't put its own or its product's name on the website. As AdWeek pointed out when the campaign launched, "One of the advantages of taking the unbranded route for Androgel is that the company does not have to warn consumers quite so prominently about Androgel's side effects."
We all remember the time during our teens where our body underwent majority of its changes that led us into adulthood. As far as testosterone levels go, this period of time is where the production of this hormone peaked. Testosterone levels during these teenage years remain high and consistent, and therefore it is not advisable to use a testosterone boosting supplement during this time. This is because, Natural Testosterone Boosters work by encouraging your body to increase it;s natural levels back to their maximum capacity. If your body is already producing it’s maximum amount of Testosterone, these products will be ineffective for you. You should be prioritising quality, intense training sessions with adequate nutrition, rich in protein and carbohydrates to elicit growth and repair.
Testosterone treatment is unequivocally needed in classical hypogonadism for reasons discussed in subsequent subsections. In classical hypogonadism, testosterone production is usually clearly below the lower limit of normal and patients are highly symptomatic; the various symptoms are easily related to the deficiencies in various bodily systems where testosterone action is important. Symptoms of testosterone deficiency are listed in Table 2. A few prominent causes of classical hypogonadism are listed in Table 3.
“This study establishes testosterone levels at which various physiological functions start to become impaired, which may help provide a rationale for determining which men should be treated with testosterone supplements,” Finkelstein says. “But the biggest surprise was that some of the symptoms routinely attributed to testosterone deficiency are actually partially or almost exclusively caused by the decline in estrogens that is an inseparable result of lower testosterone levels.”

Individuals with metabolic syndrome are at increased risk for developing coronary artery disease and diabetes mellitus. Predicting who might develop the metabolic syndrome would allow preventive measures to be taken in addition to weight control and other lifestyle modifications such as cessation of smoking and increased exercise. It is known that with decreasing testosterone availability in aging males there is an increase in fat mass and decrease in lean body mass (van den Beld et al 2000), there are disorders of insulin and glucose metabolism (Haffner et al 1996) and dyslipidemia (Tsai et al 2004). Kupelian and colleagues (2006) in analyzing data from the Massachusetts Male Aging Study demonstrated that men with low levels of testosterone, sex hormone-binding globulin, or clinical androgen deficiency, especially men with a BMI of greater than 25, were at increased risk of developing the metabolic syndrome and hence, diabetes mellitus and/or coronary artery disease.
Such sort of injuries varies in severity and extent of damage markedly from one person to the other and withdrawal of the drug/supplement coupled with proper medical attention suffice in terms of alleviating the symptoms.[8,12] This was observed in the present case. However, the liver injury observed here may not be confidently linked to product consumption as the subject later reported that the following recovery he consumed two more courses of the booster with no side effects. Tests performed following hospital discharge, and repeated use of the product showed AST and ALT to be slightly high, whereas the rest of the blood parameters tested appeared to be normal. The AST/ALT ratio is considered to be a very important parameter for the evaluation of liver diseases, such as non-alcoholic fatty liver disease,[13] though it is rarely considered alone. Overall, the evidence was inconclusive in the present work in terms of linking the use of a testosterone booster with liver injury. However, even though a single case report cannot establish causality with statistical power.[13] Further research on the usage of a commercial testosterone booster within large populations for a long period is necessary to investigate whether the symptoms shown in the present case were significantly present in other athletes consuming the same commercial product or not. To guarantee an optimal outcome with no severe side effects, further research is warranted to confirm the present findings and determine whether the effects observed in this case report would be statistically significant in larger samples.

I highly recommend using a great essential amino acid mix post-exercise in order to boost testosterone.  These essential amino acids and especially the concentrated branched chain amino acids leucine, isoleucine and valine stimulate muscle protein synthesis.  Getting these amino acids in the post-workout window dramatically boosts testosterone production (14).  I like using our Amino Strong and will often recommend a scoop pre-workout and post-workout for the best muscle building, testosterone boosting benefits.

The converse is also true; there is an increased incidence of rheumatic/autoimmune disease in men with hypogonadism. Jimenez-Balderas et al (2001) carried out neuroendocrine, genetic and rheumatologic investigations in hypogonadal men. Of the 13 hypogonadal patients, 8 (61%) had rheumatic autoimmune disease (ankylosing spondylitis, systemic lupus erythemetosus, rheumatoid arthritis, dermatomyositis). There is a low frequency of those diseases (0.83%) in the general population.
Testosterone functions within the brain. There are several lines of evidence for this: there are androgen receptors within the brain; testosterone is converted to both dihydrotestosterone (DHT) and estradiol by the actions of 5-α-reductase and aromatase respectively in the brain; steroid hormones promote neuronal cell growth and survival (Azad et al 2003). Testosterone enhances cerebral perfusion in hypogonadal men and that perfusion takes place specifically in Brodman areas 8 and 24, regions of the brain that are concerned with: strategic planning, higher motor action, cognitive behaviors, emotional behavior, generalized emotional reaction, wakefulness and memory (Greenlee 2000; Azad et al 2003). Studies of cognition demonstrate that older men with higher levels of free testosterone index (a surrogate measure of bioavailable testosterone) have better scores in tests of: visual memory, verbal memory, visuospatial functions and visuomotor scanning. Hypogonadal men have lower scores in tests of memory, visuospatial function, with a faster decline in visual memory (Moffat et al 2002). In a very small, short term placebo-controlled study hypogonadal men with Alzheimer’s Disease (AD) treated with testosterone demonstrated a modest improvement in a cognition assessment score in AD (Tan and Pu 2003).
Testosterone makes a contribution to nitric oxide formation. Nitric oxide, released from penile nerves stimulates guanylate cyclase which catalyzes the transformation of guanosine-5-triphosphate into 3′,5′-cyclic, guanosine monophosphate (cyclic GMP). Gyclic GMP causes vasodilatation and hence erection formation (Morelli et al 2005). The breakdown of cyclic GMP to GMP is mediated by the enzyme, phosphodiesterase type-5, the inhibitors of which (eg, sildenafil citrate) enhance erection formation and maintanence (Carson and Lue 2005).
Popular through the centuries in Ayurvedic healing (a traditional practice of medicine in India) ashwagandha is what is known as an "adaptogen." This means the body may be able to use it to help adapt to stressors. While many people supplement with it for reducing cortisol, anxiety, and fatigue levels, ashwagandha also holds relevance for us here with potential testosterone boosting benefits.[8]
For example, the study published in Obesity Research tells that the scientists measured testosterone levels in two groups of middle-aged men with obesity. One group underwent a 16-week weight loss program, while the second group did nothing. Each participant of the first group lost 20 kg on the average. And these participants experienced a significant increase in testosterone levels. So, the fight against overweight is very important for those who want to overcome testosterone deficiency. But starvation is strictly forbidden because this is a stressful situation which leads to the sharp decline in T levels.
Jason, if you look closer you will see that Test Freak did not make it onto our list. Both Test Freak and Zeus were only used in our introductory image to show diversity among test boosters. Despite this, I still would favor Test Freak over Anabolic Freak on the basis that Anabolic Freak’s primary active ingredient is D-Aspartic Acid, while Test Freak contains a wider spectrum of active ingredients including proprietary Testofen and Trigotest along with a good dose of Zinc.
Autopsy studies have found histological prostate cancer to be very common, with one series showing a prevalence of greater than fifty percent in men over age sixty (Holund 1980). The majority of histological cancers go undetected so that the clinical incidence of the disease is much lower, but it is still the most prevalent non-skin cancer in men (Jemal et al 2003). Prostate cancer is also unusual in comparison to other adult cancers in that the majority of those with the disease will die of other causes. Treatment of prostate cancer with androgen deprivation is known to be successful and is widely practiced, indicating an important role for testosterone in modifying the behavior of prostate cancer. In view of this, testosterone treatment is absolutely contraindicated in any case of known or suspected prostate cancer. The question of whether testosterone treatment could cause new cases of prostate cancer, or more likely cause progression of undiagnosed histological prostate cancer that would otherwise have remained occult, is an important consideration when treating ageing males with testosterone.
Testosterone was first used as a clinical drug as early as 1937, but with little understanding of its mechanisms. The hormone is now widely prescribed to men whose bodies naturally produce low levels. But the levels at which testosterone deficiency become medically relevant still aren’t well understood. Normal testosterone production varies widely in men, so it’s difficult to know what levels have medical significance. The hormone’s mechanisms of action are also unclear.
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