A Short List of Biological Interventions That Improved My Life

The following is a list of biological interventions that have helped me with energy levels, mood, well-being, cognition, and general health.

I differentiate between “soft” and “hard” based on how risky something is and whether access to prescription drugs is needed.

“Soft” interventions

Sleep

• Good sleep improves all aspects of my health & well-being. If my sleep is crap, everything is crap.

• For me, regularity is key. Going to bed at the same time every day (+/- 30 minutes) improves all aspects of my sleep.

• Light is picked up by the retina and transmitted to the brainstem, where it interferes with sleep even if I do not consciously notice it. I use blackout curtains & magnetic tape.

• The same is true for sounds. Noises impair deep sleep even if I am not aware of it. Using earplugs has considerably improved my sleep quality.

• Whenever I go to bed in a cold environment, I fall asleep faster, and I sleep better. Year-round I use a cooling blanket made of nylon and polyethylene. During the summer months, I often use a Chili Pad.

• I expose myself to bright blue light in the morning. I put on light therapy glasses immediately after waking up and leave them on for about 30 minutes. This not only helps with the entrainment of my circadian rhythm, but also improves my sleep, hormones, energy levels, and mood.

• In the past, I abused melatonin as a sleeping pill. However, I stopped using it as it might blunt the secretion of multiple other hormones.

• Before sleep, I take 5 grams of glycine and 400mg of magnesium, both of which improve my deep sleep slightly.

• Occasionally, I use a low dose of a sleeping pill.

• I discuss my sleep optimization protocol in more detail here.

Exercise

• Other than high-quality sleep, there are few things that have a greater impact on my vitality than consistent, high-quality exercise. Regular exercise improves metabolic health, musculoskeletal health, brain health, and brain function. It also improves my energy levels, cognition, and mood.

• I combine different kinds of exercise types (resistance training, aerobic exercise, high-intensity exercise, mobility training) because they all have (partially) independent benefits.

• I do about three hours, each one hour long, of steady-state cardio per week. Of this, I spend about 10% in the “high-intensity zone”, with a heart rate target of about 170-190 bpm. Aerobic exercise (“cardio”) is not just great for my metabolic and cardiovascular health, but, according to available data, one of the most powerful things I can do for my overall brain health. A good heart rate target is 180 minus my age.

• I go to the gym three times per week and do a full-body workout. I carry a decent amount of muscle mass, which is not just beneficial for feeling more comfortable in my body but is also known to prevent musculoskeletal decline and to improve metabolic health.

• For me, caring about my physical fitness was a gateway drug to general self-improvement.

• I discuss my exercise regimen in more detail here.

Diet

• In my opinion, going from a crappy diet to an “okay” diet gives huge benefits but going from an okay to a “perfect” diet (whatever that means) has a pretty bad cost-benefit ratio. In the past, I cared about my diet more than I should have, and perfectionism took away from life enjoyment and caused me a lot of unnecessary stress. Now, I only adhere to a couple of loosely held rules, which I believe provide the bulk of the benefits that can be maximally attained through dietary intervention.

• I match my carbohydrate intake to my leanness and activity levels. The leaner and more active I am, the more carbohydrates I need.

• I avoid overly processed food most of the time. Processed foods have several things wrong with them: A lot of sugar and salt, a lack of fiber, excessive amounts of omega-6 fatty acids, a lot of additives, and usually a high caloric density.

• I eat sugar sparingly. Firstly, it is addictive. Secondly, fructose is metabolized differently than glucose contributing to weight gain and insulin resistance.

• Perhaps the single most important dietary factor is caloric intake. Undereating is just as bad as overeating. In the past, I often neglected this point, and I had to pay for it.

• For a long time, I used a low dose of semaglutide, which modifies the homeostatic and hedonic aspects of feeding, to decouple my appetite from my caloric intake. While doing this, I rarely thought about food. For me, semaglutide had been a huge hack for my productivity, looks, and well-being. I recently came off because I wanted to gain body mass.

• I found intermittent fasting and a ketogenic diet temporarily useful. However, both of these caused a “crash” down the line. The “crash” was brought about in part by declines in leptin levels, sex hormones, thyroid hormones, and cortisol.

• I pay attention to how certain foods make me feel. I react somewhat badly to eggs (but only if I eat them frequently). Most “objective” food sensitivity tests are not very useful. The best way to test for food sensitivities is through a boring but cumbersome elimination diet. Some people may have immunological reactions against the following foods, which often manifest as unusual tiredness and brain fog:
  • Dairy: Some people are immunologically sensitive toward the A1-casein fraction.
  • Nuts: To prevent immune sensitization, I find it best to rotate different nuts.
  • Grains: Some people seem to react badly to grains.
  • I share my thoughts on dairy, grains, and gluten in more detail here.

• I tried to go vegan for ethical reasons though I stopped. A vegan diet is probably not optimal from a health and performance aspect. To make up for the shortcomings of a vegan diet, a vegan friend does the following:
  • He supplements nutrients missing or found only in meager quantities in plant foods: high-quality protein, creatine, choline, beta-alanine, taurine, carnitine, calcium, magnesium, zinc, omega-3 fatty acids.
  • He regularly checks his iron and B12 levels, and if necessary, supplements with these.

• Diet is discussed in more detail here.

Supplements

• I supplement with 400mg of magnesium per day (not the oxide form). I do this because most of our soils are quite deficient in magnesium due to current harvesting practices. Magnesium is needed for hundreds of different enzymes. I take magnesium before sleep because it supposedly increases sleep quality.

• I supplement with two grams of Omega-3 fatty acids (EPA & DHA) per day. I use fish oil in liquid form as capsules often have unnecessarily high amounts of Vitamin E. Omega 3 fatty acids are important for a lot of different things. Among others, they are known to improve metabolic health, lipid markers, inflammation, cognition, and mood, and (possibly) reduce all-cause mortality. Some researchers hypothesize that most people are deficient in Omega 3 fatty acids by a factor of 5-10.

• I supplement with 3.000 IU of vitamin D per day. This seems to be a dosage that can be safely taken long-term. Vitamin D is a steroid-like hormone that affects about 5% of the human genome with downstream effects on cognition, mood, immune regulation, and bone metabolism.

• I take a lot of other supplements. Most of them are just taken in a “just-in-case” mentality and I do not notice anything whether I take them or not. Many of these are presumably close to worthless, though I do not know which ones. I discuss the supplements I take, and why I take them, in more detail here.

• I experimented with a couple of herbal supplements but for a variety of reasons, I decided to avoid herbal supplements altogether. I discuss the reasons behind this in more detail here.

Hormones

• I deeply care about my hormonal profile. Whenever one of my major hormones (thyroid, sex hormones, cortisol, leptin) is off, this is a bottleneck for my energy levels, mood, sleep, motivation, and general health – and no drug or supplement can remedy that.

• Four times per year I get my hormones checked out.

• I am currently on TRT “lite”. Essentially, I take 100 IU of HCG per day. On this dose, my T levels are around 1000ng/dl, my E2 is at around 40pg/ml, and I am not even shut down (my LH and FSH are at the bottom of the normal range). I describe my first run with TRT here. This time, my experience was much better, presumably because many other things had been fixed. I will publish an article about my “TRT lite” experience soon. In order to not virilize too much from the increased androgen exposure and to age “more gracefully” (from a visual perspective) I take a very low dose of finasteride (0.125mg/d) along with it. Background: Individuals with hypogonadism look much younger than they are vs. people on TRT (after a couple of years) usually look much older than they are. Article about finasteride soon as well.

• I found out that I have rather low thyroid hormones (but still well within the “normal” reference range). Because lifestyle interventions did not make a difference, I used to supplement with them to bring them from the “medium-low normal” to the “medium-high normal” range. Supplementing with thyroid hormones, in particular a low dose of T3, has considerably improved many aspects of my health, energy levels, sleep, and life enjoyment. I recently came off because for some reason my thyroid axis had naturally improved over time.

• Whenever I am not eating enough, my hormones decline across the board. This is partly related to a drop in leptin levels. In the past, for two years, I supplemented with a low dose of metreleptin (synthetic leptin) to keep my body fat levels low without starvation-induced counteradaptations (e.g., fatigue, hunger, drop in libido, etc.).

• On and off I use a topical 17-beta estradiol cream for facial skin care (the same product postmenopausal women use for HRT – I just use a much smaller dosage).

• I have experimented with a variety of different hormones, among them testosterone, cortisol, leptin, and growth hormone…and about a dozen others. I discuss my experience and hormone basics in more detail here.

Blood test

• I get regular blood tests, ready to intervene accordingly. I test for the following parameters at least once per quarter:
  • Hematology, liver enzymes, kidney markers
  • Uric acid, homocysteine
  • Triglycerides, ApoB
  • Ferritin, vitamin D, vitamin B12
  • TSH, fT3, fT4
  • LH, FSH, SHBG, total testosterone, E2
  • DHEA-S
  • CRP
  • IGF-1
  • Leptin
  • CMV-IgG

• Occasionally I wear a continuous blood glucose monitor (CGM)

• Every other year I also test for some other markers, which I share here.

“Hard” interventions

As with everything on this blog, the following represents what I found works for me personally (n=1). We are all different.

I found that my response to a certain pharmaceutical, and in particular neuropharmaceutical, is a very individual thing, and it is awfully hard to predict how I respond to something, regardless of what doctors, the medical literature, or anecdotal online reports make me believe. The only way to figure out how I respond to something is to try it.

A list of molecules I have experimented with can be found in the Experience Reports section.

Sleep drugs

• Sometimes I find a low dose of zopiclone or triazolam useful. I take a low dose of eszopiclone occasionally to “guarantee” a restful sleep and I take a low dose of triazolam occasionally whenever I have a particularly hard time falling asleep. If taken occasionally, the risks and side effects of sleep drugs need to be weighed against the risks and side effects of shitty sleep.

• Continuous use (i.e., non-occasional use) of CNS depressants such as benzodiazepines, Z-drugs, gabapentinoids, and antihistamines seem to be associated with progressive low-grade cognitive impairment, and therefore I believe that they should only be reserved for severe cases, and ideally, for only a short period of time.

• I discuss the sleep drugs I have experimented with in more detail here.

Stimulants

• In general, I am best off if I do not take any stimulants at all. I find that stimulants are mostly “borrowed energy” and the only exceptions I have ever found are nicotine and moclobemide.

• My favorite stimulant has become yohimbine and it is essentially also the only stimulant I currently ever use. Whenever I need a push, I take 1.25mg of it. I am a homozygous CYP2D6 poor metabolizer so for me the yohimbine lasts considerably longer than for normal metabolizers. I “feel” stimulated from the yohimbine for roughly 4 hours. No comedown. Just very clean energy. Article about yohimbine soon.

• I recently started using pitolisant. Super interesting molecule. It elevates central histamine levels and gives wakefulness without any stimulant effects (i.e., unlike modafinil and other stimulants). Article about it when I have a better grasp on its long-term effects on me.

• In the past, I was addicted to caffeine. After coming off, I found out that I had considerably better sleep and daytime energy without it. Ever since, I have been using caffeine only very rarely and strategically.

• During university, I often used modafinil. However, it impairs my creativity and sleep and therefore I barely ever use it anymore. Like other stimulants, there is counterregulation associated with its use, which worsens my baseline. I now use a very low dose of modafinil about once or twice per month.

• Sometimes I use nicotine gum during cognitively demanding tasks. Another upside is that I can use it at night without it impairing sleep. I prefer slowly absorbing delivery vehicles such as gum and sublingual tablet, and I only ever use flavorless products, as having something sweet in my mouth decreases executive functions for evolutionarily obvious reasons. The major downside is that it is addictive.

• I avoid amphetamines because most people using them seem to be much worse off in the long run, despite benefiting for a couple of months, sometimes years. After coming off, many people report hardcore withdrawal and anhedonia. It may also be that amphetamines are detrimental, presumably even toxic, to long-term brain health, especially the dopaminergic system.

• For me, most “nootropics” I have tried were worthless. The ones that may be not, such as racetams or noopept have little credible safety data or manufacturer quality control.

• Stimulants are discussed in more detail here.

• For a list of stimulants I have experimented with, see here.

Antidepressants & similar molecules

• By far the #1 thing for my vitality is having an amazing group of friends and spending much of my free time with people I value. Furthermore, having purpose and a fairly set direction in my life is also having a big top-down effect on my physiology and neurobiochemistry. I´ll just briefly mention this even though that is not what this website is about. Both, having purpose and high-quality human connection are very antidepressive, presumably via a “top-down”-mechanism. This is quite unlike the bottom-up effect that comes from chemical stimulants or antidepressants.

• Ashwagandha and rhodiola worked well for times I was heavily stressed, however, for a variety of reasons I decided to stop herbal supplements altogether. Because I have already decided to use exogenous molecules to influence my physiology, in my opinion, there is no difference in principle between taking herbals or a prescription drug.

• In terms of recreational drugs, once a month to once every other month I take a low dose of plant medicine (0.5-1g) to have “a month’s worth of psychotherapy in one afternoon” and to get some “death-bed” clarity. Occasionally I also take a low dose of 1,4-butanediol – a great replacement for ethanol, which I never to rarely (once per year) drink.

• When I was depressed a couple of years ago, vortioxetine was a great general-purpose anti-depressant. It boosted my mood, energy levels, stress resilience, confidence, and cognition while having few adverse effects on sleep, libido, emotionality, or weight. I found it to be a little different from other SSRIs.

• My personal favorite antidepressant is moclobemide, which I never used as an antidepressant but rather as a “lifestyle drug”. For me, moclobemide was a great allrounder. It improved my energy and mood while having no side effects other than a subtle emotional and cognitive blunting. Moclobemide made me a slightly happier, a slightly more productive, and slightly “better” human being. I took a very low dose of rasagiline with it to balance out the dopamine-serotonin ratio. I stopped it because on it, my IQ is roughly 10 points lower.

• For two friends with treatment-resistant depression, irreversible MAOIs have been the only antidepressants that have ever worked. However, they come with significant risks, including life-threatening interactions if combined with molecules that react on serotonergic or noradrenergic systems. Furthermore, they have nasty side effects, particularly debilitating hypotension, lethargy, and insomnia.

• On and off I use pharmaceutical grade NSI-189, which is a stimulator of neuroplasticity/neurogenesis. On it, I dream a lot and my libido is undeniably higher. I also seem to have more emotions in general. I will test it for a little longer before I write an article about it.

• From time to time, I struggle with anhedonic depression. This happens about 3-5x per year lasting a couple of weeks. During these times, I do all the things I normally do (e.g., work, gym, friends) but I feel quite little. A single dose of ketamine has thus far always been sufficient to kick me out of it I am always reluctant for a couple of weeks to use it because it is probably more neurotoxic than science currently appreciates. If the “waiting it out” does not work, 24 hours after the ketamine injection, I feel like my brain can “breathe” again and it seems as if somebody has turned my feelings back on and usually they remain on for at least a few weeks, sometimes months. I aim to not use it more often than once a quarter or less. Ketamine works wonders for a colleague whenever biological depression is looming. Besides the fact that some people do not respond at all, there is evidence that ketamine may be neurotoxic, perhaps already at therapeutic doses and frequencies.

• A couple of my friends were addicted to weed. Even though they believed it helped them, not until they stopped, did they realize that their baseline level of motivation was worse, and anxiety was higher during the times they were using. Furthermore, they now realize how bad it was for their cognition, and life overall. Three of my friends found bupropion useful to help with coming off. Bupropion boosts energy levels, mood, motivation, and focus – all of which are helpful when trying to kick an addiction. Bupropion is also a great antidepressant.

• Antidepressants & related molecules are discussed in more detail here: What Kind Of Antidepressant Should I Take?

Metabolic health

• Metabolic health is not just the cornerstone of longevity, but also of general health. The best proxy for metabolic health is insulin sensitivity, which I occasionally measure with a continuous glucose monitor. The most important pillars of great metabolic health are watching my body fat, daily exercise, diet, sleep, and having a good hormonal profile.

• I have experimented with a number of drugs that influence metabolic health, including metformin, SGLT-2 inhibitors, GLP-1 agonists, and acarbose. I currently use none of them.

• I have recommended GLP-1 agonists to a couple of friends who were overweight (and now they are not anymore). Being overweight is the #1 reason for bad metabolic health. According to the available literature, GLP-1 agonists are by far the best intervention currently available for appetite control and weight loss.

• Metabolic health is discussed in more detail here.

Longevity

• I care about preventing cardiovascular disease, which kills about 50% of people in Western countries. Besides not smoking, I watch my blood pressure, insulin sensitivity, and ApoB levels. If any of them were out of order, I would use lifestyle & drugs to optimize them.

• I do not bother with useless supplements such as NMN/NAD or resveratrol.

• I take a weekly dose of rapamycin. According to the currently available data, rapamycin is presumably the most potent geroprotective molecule currently available to mankind. However, there is little long-term efficacy and safety data on intermittent dosing used for longevity purposes. Furthermore, whether rapamycin is as potent in larger mammals (e.g., humans) as it is in smaller ones (i.e., rodents) is unknown. Nonetheless, after thoroughly researching the molecule and speaking with two doctors who take it themselves, I decided to take it. I have been on it for a little over four years, while regularly checking several lipid, metabolic, immunological, and general health markers. I discuss my experience with rapamycin in more detail here.

• I discuss my approach to longevity in more detail here. The more technical version can be found here: My Longevity Protocol (Long & Technical Version)

For a list of many other strategies & molecules click here: Browse By Topic

Disclaimer

The content available on this website is based on the author’s individual research, opinions, and personal experiences. It is intended solely for informational and entertainment purposes and does not constitute medical advice. The author does not endorse the use of supplements, pharmaceutical drugs, or hormones without the direct oversight of a qualified physician. People should never disregard professional medical advice or delay in seeking it because of something they have read on the internet.