All about Testosterone

Admittedly this blog post has very little to do with Intermittent Fasting, but I’ll do my best to tie it all together in the end.

Instead of fasting, today we’re talking about Testosterone. And, although the name testosterone is only 65 years old, the hormone that it identifies has been a focus of scientific interest for more than a century.

I would argue that its influence on masculinity has made Testosterone the most controversial hormone in the human body, and that this controversy has left the average person blind to its potentially therapeutic properties and benefits.

However, despite the common belief, there is a lot more to Testosterone than baseball and bodybuilders.

For the purpose of keeping this post under 10,000 words we’re going to be mostly exploring testosterone in men, but I will point out some of the facts that apply to women as well.

All right, lets get started.

The basics of Testosterone are fairly easy – Men have much more than women and this difference in circulating testosterone levels is largely responsible for the main differences between the sexes (muscle mass, body fat storage patterns, body hair etc).

Testosterone secretion in men follows a circadian rhythm^[i]. This is just a fancy way of saying that the amount of Testosterone in your blood varies depending on the time of day. Peak serum testosterone levels in men occur between 5:30 AM and 8:00 AM and then slowly taper off towards the end of the day then start to rise again during the night ^[ii],[iii].

It is also well known that Testosterone plays an important role in the development of skeletal muscle size ^[iv]. There is a well established dose response between average serum testosterone and muscle mass. This includes levels in the extremely low range all the way into ‘supraphysiologic range’ – the levels only possible with testosterone injections, or really rare disease states.

Actually, funny story about the above statement… Back when they first declared the ‘war on steroids’ the experts tried to tell people that testosterone didn’t actually work. That it didn’t increase strength or muscle mass… Oops. 😉

OK, so we know Testosterone is a hormone that is found in high levels in men and is at least partly responsible for the fact that men typically have more muscle mass then women, but what is not really well known is how eating affects Testosterone levels.

Surprisingly, the very act of eating just about anything over 300 calories causes a decrease in Testosterone levels in healthy men and this decrease can remain significant for more than 3 hours after the meal^{[v], [vi], [vii],[viii]}. Even meals under 300 Calories may have an effect, I just wasn’t able to find any studies that used anything under 300.

And it doesn’t have to be a ‘mixed meal’ containing carbs, fats and proteins.  Even a single oral glucose tolerance test (Basically a drink containing 75 grams of glucose) can decrease testosterone levels in men with good glucose sensitivity, bad glucose sensitivity and even in diabetics ^[ix].

The odd thing about testosterone is that while sugar, fat, and protein all decrease testosterone levels acutely, they seem to have differing affects chronically.  Acute high fat intakes lower also testosterone, however chronic high fat intake may slightly increase serum testosterone levels ^[x],[xi]

And while acutely high protein meals are known to decrease serum protein levels, chronic protein malnutrition has also been shown to cause sustained decreases in serum Testosterone levels^[xii].

Even more interesting the source of protein may also affect serum testosterone differently as well as if you’re looking at a single meal or chronic habitual intake. Both meat and tofu decrease Testosterone in a single serving⁶_.  However, switching from a meat based diet to a lacto-ovo vegetarian diet can decrease serum testosterone and the testosterone response to exercise. (protein intake remained equal)^[xiii].

So right away it becomes clear that there is an abundance of research showing that not only does nutrition affect testosterone levels in men, it does so in one general direction. Down.

However, we also know that fasting for long periods (over 50 hours) starts to cause a decrease in testosterone^[xiv], and fasting for more than 10 days causes significant decreases in Testosterone^[xv]. So it’s not like you can just ‘not eat’ and have super high Testosterone levels.

Based on these findings it’s already clear that there is a difference between fasted state Testosterone levels and fed state testosterone levels. But lets be careful with how we word these things: It would be incorrect to say that fasting is able to ‘boost’ or ‘raise’ testosterone. It would however, be correct to say that eating does decrease testosterone levels from the level seen in the fasted state.

OK, so eating decreases testosterone from the higher fasted level, but not eating for too long can also cause testosterone to decrease. Just about all foods decrease testosterone however a higher-fat lower-protein diet seems to slightly increase testosterone levels in the long term, as long as the protein intake isn’t too low.

Confusing I agree. Basically from the available research it is obvious that testosterone is actually highly sensitive to acute chronic intake. However, what we still don’t know is while these findings are clinically significant, do they actually influence muscle mass or health? To answer this we need to move on to the research on exercise and testosterone.

It’s fairly well accepted in the scientific community that resistance training (but not too much of it) increases Testosterone levels in the hours after the workout ^{[xvi],[xvii],[xviii],[xix],[xx],[xxi].}

It is interesting to note that while all the studies referenced above showed a training induced increase in testosterone, the one study that did not show an increase (and in fact a decrease) had people doing a massive amount of exercise in one workout – 50 sets combined of squats, bench press, lat pull down, and leg press. These poor guys saw a decrease in both testosterone and free testosterone that lasted for 13 hours. It would appear that training past your limits can depress testosterone levels. Just something to remember next time you decide to do a marathon weight training sessions that is well outside your typically volume of training.

Since most research has found that training increases testosterone it’s interesting to explore what happens to the training induced rise in Testosterone when you eat after your workout.

Surprisingly (at least to me) when exercise is followed by the consumption of carbohydrate and/or protein, testosterone values fall below resting levels in resistance-trained men^[xxii].

This drop in testosterone is not observed in trained men who consume a placebo following exercise^[xxiii].

However, while acute meals after training seem to negatively affect the testosterone response to a workout, the resistance exercise induced increase in Testosterone does not appear to be affected by nutrition variables averaged over 17 days. So your typically way of eating has very little effect on the testosterone release that happens after a workout^[xxiv].

The importance of testosterone in strength-training-induced muscle hypertrophy seems clear – Testosterone is directly involved in the muscle building process^{[xxv],[xxvi],[xxvii]. However, recent research has shown that the acute increase in testosterone that occurs after weight training is not solely responsible for the muscle growth caused by weight training – there are definitely other factors at play[xxviii].}

We know that post-workout nutrition in the 24 hours after a workout are involved in the anabolic process (especially protein), however the importance of acute testosterone in strength-training-induced muscle hypertrophy seems less clear^25,26,27_.

So what gives?

Post workout nutrition is important for optimal muscle growth, testosterone is important for optimal muscle growth, but post-workout nutrition lowers testosterone levels?

Most likely there are a number of factors at play. First we need to remember there is a difference between chronic and acute levels of hormones. In this case chronically high testosterone is associated with higher amounts of lean body mass, but acute changes (the short term increase after a workout) may not be significant to the muscle building process.

Second, testosterone isn’t the only factor in muscle building. There is evidence suggesting that even when testosterone levels are chemically suppressed many of the adaptations to resistance training still occur, but to a lesser extent^[xxix].

Testosterone is very important to muscle building, but muscle building can occur with low levels of testosterone, see the jacked girl at your gym as an example (the ones not on drugs)

Considering the multiple components and systems involved in regulating muscle growth, I would say that it’s a myopic mistake to assume that ONLY testosterone, or ONLY Insulin or ONLY mTOR is the key to muscle growth, when it’s most likely a specific hormonal/nutrient combination (probably even in some sort of optimal order) that leads to lasting noticeable changes in muscle size.

In fact, it appears the anabolic response involves at least two separate processes – The accumulation of specific proteins involved in the enlargement of muscle fibers (possibly Amino acid driven) and the proliferation and differentiation of satellite cells providing additional nuclei to the enlarging muscle fibers (possibly testosterone driven) ^4,[xxx].

Obviously there is way more to it than this simplified explanation, but the fact remains…you need a bunch of things to be optimal for muscle to grow, not just protein intake or Testosterone levels.

We can see that Testosterone levels are affected by both resistance training, nutrition and their combination, and that these effects are actually opposite of what we (or at least I) have been lead to believe.

We also have evidence that overall testosterone levels seem to be more important than small acute dips or increases when it comes to muscle mass and possibly overall health (more on that later)

I promised I wouldn’t turn this into a post on intermittent fasting, but if the above research is correct then it kind of makes me think that training after a fast, then eating, may be the best of both worlds. But who knows, it could be the opposite (eat, then train, then fast). Point is, there isn’t much research in this field that gives us clear answers. Anybody who tells you otherwise is theorizing more than I am currently comfortable with.

Next up is the role that body fat plays in the amount of Testosterone we have.

The bad news is obesity is associated with low testosterone levels in men. The worse news is that the more obese a men gets (especially belly fat) the lower testosterone levels seem to get.  The good news is losing weight is associated with an improvement in testosterone levels^{[xxxi],[xxxii],[xxxiii].}

Visceral adiposity (deep down belly fat) is associated with production of inflammatory cytokines and increased aromatization of testosterone to estradiol, leading to decreased testosterone levels and decreased testosterone production^{[xxxiv],[xxxv]}. Basically as body fat goes up, testosterone goes down…unless you are a women, in which case it will go up.

The relation between waist circumference and levels of testosterone has been found to be different depending on whether you are a man or woman. A larger waist circumference was associated with low testosterone in men, whereas in women, a bigger waist circumference was associated with high testosterone^[xxxvi].

This last statement should be super important to you since the one paper published in the 1980’s by Forbes et al. that ‘proved’ that overeating boosted anabolic hormones was conducted on women. (Gender differences are important)

So now we have a connection between Testosterone and nutrition, testosterone and resistance training and Testosterone and body fat. And we also have the gender difference in the relationship between Testosterone and body fat. Which, by the way in my opinion just makes obesity even worse… men lose testosterone but women gain it, just seems so unfair to someone already suffering from obesity.

The connection between testosterone and body fat immediately made me think of the hormone Leptin.

Leptin is a hormone connected to nutrition and body fat and is blunted by exercise. It is released by fat cells and is monitored by the brain.  Levels of leptin in your blood correlate to the amount of body fat you have and is also correlated to the amount of food you eat .  High levels of leptin are found in obese people, while low levels are found in long term starvation.

Epidemiological and experimental data support the idea that testosterone has a negative influence on leptin levels in men, or at least a negative correlation^{[xxxvii],[xxxviii]}.

Testosterone administration reduces leptin levels in men with low testosterone levels or normal testosterone levels, and in adolescents with delayed puberty. Furthermore, increasing levels of testosterone parallels a decline in leptin levels during puberty^{[xxxix],[xl],[xli],[xlii],[xliii],[xliv],[xlv]}.

Injecting ‘bodybuilder’ amounts of steroids into otherwise healthy men causes large scale reductions in circulating leptin levels, that eventually return back to normal levels even after more than six weeks of heavy steroid use. Also, giving healthy normal weight men a drug to suppress testosterone levels causes a rapid and lasting rise in leptin levels^[xlvi].

In fact, even giving either young or elderly men an anti-aromatase drug that stops the conversion of testosterone to estrogen is able to lower Leptin levels, and this is without increasing Testosterone into the supraphysiological range^[xlvii].

In fact, an inverse association between androgens and leptin has been shown repeatedly in healthy middle-aged and in older men. As men age leptin tends to increase as testosterone levels tend to decrease^{[xlviii],[xlix],[l],[li],[lii]}. Interestingly, in men being treated with testosterone, the age related increase in leptin did not occur^[liii].

It seems clear from this research that as Leptin goes up Testosterone goes down, and as Testosterone goes up, leptin goes down…. Unless you are a woman

In women the opposite relationship between androgens and obesity is present: testosterone is positively correlated with BMI and leptin levels[liv],[lv],[lvi]. So as obesity goes up so does Leptin and Testosterone in women.

These findings really help us understand why Leptin levels are always higher in women, the difference seems to be driven by the sex hormones^{[lvii],[lviii],[lix]}. It also shows us that we ALWAYS have to be aware of the possibility of gender differences when we explore how the human body works.

Interestingly, Leptin and Testosterone seem to have an inverse relationship, yet Testosterone seems to have a dose dependent effect on whole-body fat mass in healthy young men^[lx],[lxi]. Which makes me wonder how much of what we know about high leptin can be attributed to low testosterone, and how much of low testosterone can actually be attributed to having high leptin. Of course this is one of the major problems in viewing the body in individual pieces instead of as a whole unit – sometimes you miss these interactions.

It’s clear that there is a very strong relationship between testosterone and leptin, however I’m not entirely sure which direction the relationship goes. I was unable to find any studies that injected leptin and measured testosterone levels in either men or women.

Regardless, I think this research is fascinating. Based on these findings, I would say that a measurement of Leptin should be made in men who are worried about their Testosterone levels. It makes sense that a leptin measurement could be used to validate a diagnoses of low testosterone, seeing as testosterone itself can be affected by acute changes in calorie intake. Along the same lines, I think anyone worried about their leptin levels should also have their Testosterone levels measured.

Another fascinating finding from this research raises the question of gender equality in diet and weight loss recommendations. Specifically should men and women follow similar diet and exercise recommendations considering the differing relationship between men, women, body fat and leptin. It especially worries me when it comes to things like ‘bulking’. In my opinion it seems the purposeful overeating and gaining of body fat in the name of building muscle may be a bad idea for both men and women.

But really, the point of the blog post was to explore testosterone and some of the effects it has on the body that you may not be aware of (not just muscle building stuff), so I’d like to explore another important area. Diabetes.

The metabolic syndrome is a constellation of metabolic risk factors (including hypertension, dyslipidaemia, abdominal obesity and impaired glucose metabolism), which is associated with a 2-fold increased risk of cardiovascular disease (CVD), and an even higher risk of type 2 diabetes^{[lxii],[lxiii].}

Low serum testosterone is common in men with type 2 diabetes and/or metabolic syndrome, and numerous studies have reported an inverse association between testosterone levels and obesity, insulin resistance and dyslipidemia. This can partly be explained by an increase of aromatase activity, which is associated with a greater conversion of testosterone to estradiol (testosterone–estradiol shunt associated with increased subcutaneous fatty-tissue)^[lxiv].

A meta analysis that included 14,319 men and 3,904 women in total found a sex difference indicating women with metabolic syndrome had higher testosterone levels, whereas men with metabolic syndrome had lower levels of testosterone than those without. Furthermore this difference remained significant after adjustments for age, diabetes and BMI^[lxv].

From these findings there is a definite relationship between Testosterone and Diabetes in men, and this relationship is strong enough that I think Testosterone should be part of the diagnosis of Diabetes.

So why isn’t testosterone used more widely in the diagnosis of these disorders?

The problem arises in the politics over testosterone. The range we consider ‘normal’ is large, more than a 10 fold difference between ‘low’ and ‘high’. However, what is low in an average healthy male, may be ‘too low’ in a diabetic. Well…maybe, maybe not, point is more research is needed in this field, research done without the stigma of testosterone being ‘bad’ or ‘for muscle only’.

I find the idea of not at least considering  treating anything outside of this range as somewhat surprising. To me, it’s like not helping anyone who’s body fat is within the ‘normal range’ of 4 and 40% body fat. Seems odd to wait until they are REALLY at risk before helping them… but I digress… and I’m not a medical doctor, so really… what do I know about treating patients (the answer is: not much)

Lastly, I wanted to touch on testosterone, depression and mood. In the past few years there has been an increase in the amount of research linking high leptin levels with depression in men.

In older men, high leptin levels were associated with an increased onset of depressive symptoms, especially in the presence of abdominal obesity^[lxvi].

Other research shows elevated leptin levels were also found in socially isolated and depressed men. This raises the possibility that increased cardiovascular mortality in socially isolated men is partially mediated by hyperleptinemia^[lxvii].

Finally, in research looking at stroke victims, serum leptin levels at discharge are found to be associated with post-stroke depression and may predict its development during the next month^[lxviii].

Looking at what we now know about the connection between Testosterone and Leptin, I can’t help but wonder if the connection between leptin and depression is really just a connection between low testosterone and depression.

First, there is a sex difference in the relationship between depressive symptoms and leptin in people with Type 2 diabetes, with a positive association in men but not in women^[lxix]. Which makes me think the connection could be Testosterone mediated.

Second, we already know that testosterone is linked to mood.

There is data that suggests normalizing testosterone levels will improve cognition and mood and perhaps even be useful in treating some persons with Alzheimer’s disease^{[lxx],[lxxi],[lxxii],[lxxiii],[lxxiv]}

If you remember from my inflammation theory research, I think that chronic inflammation is the root of a number of diseases, and it’s no coincidence that Leptin is involved in the regulation of the inflammatory response. Leptin can be viewed more as a pro-infalmmatory molecule, while in men testosterone is anti-inflammatory (Lord 1998; Boulounie 1999; Fantuzzi 2000; Caldefie-chezet 2001; Yamagishi 2001; Farooqi 2002; Glitay EJ, 2008; Hatakeyama H 2002; Liva SM, 2001)

In fact, there are already well established links between chronic inflammation and depression, diabetes, obesity, the three main topics of the blog post.

However, this relationship is skewed by the fact that the relationship between leptin and testosterone is different in men and women.

Bottom line and the actually usable information from this blog post:

 

1. This is not a blog post promoting the use of steroids. Just as there seems to be negatives in having low testosterone there are surely negatives having ultra high levels of testosterone. I’m also not suggesting testosterone is a cure all. Rather, the point is that there is a lot more to testosterone than just muscle building, and that there is a lot of exploration we could do inside of the range medicine considers ‘normal’.
2. Leptin and Testosterone should BOTH be measured in men if you think you may have low testosterone. I also think that both Leptin and Testosterone need to be studied more closely for their roles in diabetes and depression.
3. This research furthers my belief that ‘bulking’ is a bad idea, unless you are young (early twenties) or taking testosterone. As you may already know overeating has been purported to aid in the muscle building process in young, non-steroid using athletes. However this effect seems to decrease with time, leading to speculation that the slow build up of inflammation eventually reaches a point where muscle growth is blunted.
4. Eating leads to a decrease in testosterone as does increasing levels of adiposity. During prolonged periods of overeating Inflammation goes up, Leptin goes up, testosterones goes down, and testosterone conversion to estrogen increases.  Therefore unless you are young, or you’re taking testosterone, I simply do not see how prolonged periods of grossly overeating in the name of muscle is a good idea. If you are a women and considering bulking the idea also scares me a bit – lots of Leptin and Lots of testosterone worries me, but truthfully I’m not sure how big of an effect there is on women (thinking I need a women only blog post as a follow up)
5. As a general rule of thumb, never bulk to the point where your waist circumference is greater than 50% of your height (men and women).
6. There are definite gender differences in sex hormones, their interaction with leptin, obesity and probably food.  Why does Testosterone increase in women with increasing adiposity? I have no clue, but it is a very interesting finding.
7. Testosterone is involved in much more than muscle building and needs further examination in its role in diabetes, depression, cardiovascular disease, obesity and even things like leptin resistance.
8. Lastly, Based on this research I feel strongly in my convictions that ‘health’ involves keeping Calories low (but not too low), keeping body fat low (but again not too low), get lots of sleep, and avoid excessive overuse of exhaustive exercise in the name of optimal muscle growth or long term health. Train consistently, and match strenuous exercise with periods of light exercise.
9. If you are worried about your testosterone levels get it measured. If the results come back as ‘normal’ ask exactly what that means.

 

BP