What to do when biohacking isn't working

What to do when biohacking isn't working

By Jonathan Roseland

I'm not a doctor, medical professional, or trained therapist. I'm a researcher and pragmatic biohacking practitioner exercising free speech to share evidence as I find it. I make no claims. Please practice skepticism and rational critical thinkingYou should consult a professional about any serious decisions that you might make about your health. Affiliate links in this article support Limitless Mindset - spend over $150 and you'll be eligible to join the Limitless Mindset Secret Society.

Almost weekly, rather distressed people contact me privately who are sick of being sick and tired and they are frustrated because they have tried some Nootropics and biohacking stuff but to little avail.

They complain of...

  • Terrible sleep
  • Crippling fatigue
  • Bouts of depression
  • Weight gain
  • Erectile dysfunction
  • Severe social anxiety
  • Or a goldfish attention span

To these people, I recommend a three-pronged approach...

1. Disciplined habituation of lifestyle biohacks
2. Mitochondrial Nootropics
3. Testing and self-quantification

I'll go further in-depth on these three prongs (a prong would be the singular object of a three-pronged approach right? Or is a prong what Australian people call shrimp?) but first I need to clarify something. This methodology was not just conjured up by me (Mr. Unlicensed Internet Biohacker Guy who didn't even go to college), it's a distillation of the information I've metabolized from several books and the 230 scientific papers published on Mitochondria in the past year that I've either read or skimmed.

Mitochondria and the Future of Medicine I recently finished this fairly dense book by Dr. Lee Know summarizing the state of the art of Mitochondria science and research. The major takeaway from the book is that Mitochondrial dysfunction is (likely) the underlying cause of the nasty health conditions and mental illnesses that deprive us of aging gracefully and living life fully.

So how do you fix Mitochondrial dysfunction?

Sorry, there's no easy fix. Good things take time. First of all, there's all the lifestyle stuff...

  • Cut all the junk food and eat a clean keto-style diet (I'll have some broccoli with Kerrygold butter and MORE Kerrygold butter mixed in my coffee)
  • Take cold showers
  • The light hacking (no blue light before bed)
  • Meditation
  • Daily intermittent fasting
  • And cardio exercise (more on this below)

And there are a lot of other lifestyle biohacks for peak Mitochondrial function, if you'd like them organized in a cogent program, read Dave Asprey's recent book Head Strong (or at least my review of it), here...

Head Strong: The Bulletproof Plan to Activate Untapped Brain Energy to Work Smarter and Think Faster-in Just Two Weeks
Category: Book

About cardio, if you're not doing cardio regularly, DO CARDIO. From Dr. Know's book:

It’s been known for decades that aerobic exercise can increase the number of mitochondria in your muscle cells by up to 50 percent in as little as six weeks. To get the benefit , however , you need to do aerobic exercises ( such as running , cycling , swimming , or walking briskly ) at an intensity that’s at least half of your maximum capacity . This intensity needs to be sustained for at least fifteen to twenty minutes per session , three to four times a week .(3014-3017)

Wow! So you get a 50% uptick in Mitochondria in your muscles from just 15-20 minutes of cardio a few times a week. If you don't want to sprain an ankle jogging or get hit by an SUV cycling, you can do what I do and do Dual N-Back brain training on your smartphone while pedaling vigorously on a stationary exercise bike.

If your lucky genetics, 10 years of meditation, military training, or strict religious upbringing imbued you with extraordinary human willpower and you have virtuous, supportive friends and family that enable and encourage your best behavior good for you! You should have little problem hacking away the unessential; implementing and habituating those lifestyle biohacks.

If not...

it's going to be a hell of an uphill battle for you to improve your health! Statistically speaking, your chances of living a happy, healthy life are bleak. You're going to need to implement some serious willpower lifehacks, maybe strapping on that cool Pavlock device that shocks you or doing an Ayahuasca trip in Peru. You could try Oxiracetam, which I call the discipline molecule. You could hire a personal trainer or enroll in one of those Bootcamp-style fitness programs where they yell at you! You could bet your friend $1000 that you won't have a cigarette within the next 90 days or you could inquire about the Limitless Mindset minimalist life coaching program.

But these lifestyle biohacks are only half the battle...

Especially if you're dealing with mitochondria dysfunction, you'll need to use some Mitochondrial Nootropics for 6-9 months. Many Nootropics have an immediate short-term effect of making you more energetic, focused, and clear-headed BUT the human studies indicate that long-term restorative effect on your Mitochondrial function takes longer. So you'll need to commit to a medium-term relationship with them and (sorry!) it won't be inexpensive.

 Here are the supplements in approximate order of effectiveness, if your budget is limited, pick up the ones closer to the top of this list...

1. CoQ10

This antioxidant is close to being a household name and it's one of the most researched Mitochondrial support supplements. Pretty much everyone advancing through their fourth or fifth decades of life should be taking it and you definitely should if you're dealing with one of those check engine light conditions.

Now there's a catch to CoQ10, it's not very bioavailable, in fact, some forms of it are pretty useless.

Unfortunately , absorption of this rather large fat - soluble molecule is challenging , which is a main factor limiting its therapeutic use . Research has shown that oil - based formulations ( typically softgels ) are much better absorbed , and water - dispersible liposomal or pre - emulsified formulations are even better . Ubiquinol ( reduced CoQ10 ) seems to offer much better absorption than ubiquinone ( oxidized CoQ10 ) , and water - soluble ( solubilized ) ubiquinol is even better absorbed .(2364-2368)

Three vendors that meet these high standards for absorption are...

2. Piracetam

According to a 2013 University of Frankfurt paper, Piracetam is something of a Mitochondria hack.

In previous studies we were able to show that piracetam enhanced ATP production, mitochondrial membrane potential as well as neurite outgrowth in cell and animal models for aging and [Alzheimer's disease]. To investigate further the effects of piracetam on mitochondrial function, especially mitochondrial fission and fusion events, we decided to assess mitochondrial morphology... 


Carnitine increases the quantity and quality of the Mitochondria along with greasing the microscopic mechanism of fuel transport that our individual cells need to thrive. From a University of Naples study:

...ALCAR supplementation partly reduces the leptin resistance... and improves ATP production in skeletal muscle mitochondria through an increase in mitochondrial protein content.

In non-scientific terms, it helps transport fat into individual cells that need it for powerIts antioxidant mechanism may be something of a boozing biohack, according to a 2011 University of Nebraska study on the human brain and alcohol:

Mitochondrial membrane protein damage and decreased membrane potential after ethanol exposure indicated mitochondrial injury. These changes were prevented by [carnitine]. Our findings suggest the counteracting mechanisms of oxidants and antioxidants during alcohol-induced oxidative stress at the [blood brain barrier].

Lack of energy to zealously take on life is such a common symptom, that the voracious consumer has near limitless stimulant options to spike energy. Since ALCAR so profoundly affects energy generation at such a foundational level it’s a favorite of more holistic biohackers.

4. Magnesium

Unless you supplement Magnesium regularly you're probably deficient (especially if you drink a lot of coffee)...

Magnesium is likely one of the most underrated minerals and most people are just not consuming enough of it . One reason most are deficient in this mineral is that water softeners , while great for making your faucets shiny , has reduced the water’s hardness by removing minerals such as magnesium...Then there’s our rising caffeine intake , which increases the amount of magnesium we lose through urine... All these factors contribute to the alarming statistic that 70 – 80 percent of the developed world population is deficient in magnesium. (2569-2575)

Personally, given the option, I reach for the Mercedes-Benz of Magnesium, Magnesium L-Threonate. It's more bioavailable and has greater benefits to cognition but it first caught my attention for a silly reason...

About 20 years ago, before all these silly, over-commercialized Star Wars and Star Trek movies came out there was an (actually good!) Star Trek movie called Insurrection featuring Captain Picard and the rest of the Next Generation Enterprise cast. In the movie, they were in this tense political standoff with these aliens that were using these banned, illegal space weapons called ThreonateYou should watch that movie if you like science fiction and regularly supplement magnesium if you care about your Mitochondria!

5. B-Vitamins

B vitamins are crucial to healthy Mitochondrial function; specifically B3, B6, and B12.

Of all the nutrients defined as true vitamins , the ones that have the greatest direct impact on cellular metabolism and energy production are collectively known as the B vitamins . This group is made up of numerous distinct nutrients , and each is either a cofactor in an important metabolic process or a precursor of an important energy - related molecule .(2666-2669)

6. Creatine

Creatine is one of the most well-known supplements that's often caricatured as something just for gym bros because it helps them build muscle but actually, it's a veritable Mitochondrial Nootropic.

Creatine is directly related to ATP . When a cell uses ATP , it loses a phosphate molecule and becomes ADP , which must be converted back to ATP for useful energy cycling . Because creatine is stored in the body as creatine phosphate , it can donate a phosphate molecule to ADP to regenerate ATP . This process is very speedy and is the main source of cellular energy production at the start of high - intensity anaerobic activity ( such as a 100 - meter sprint or lifting heavy weights ) . Having a large pool of creatine phosphate means this fast pathway of ATP regeneration can be sustained longer , which is exactly why creatine has been so beneficial for athletes .(2640-2645)

Creatine and the brain

Because the brain and nervous system require such high amounts of energy , it’s logical to assume the neurological system can benefit greatly from creatine — and this is being corroborated by clinical research . A growing number of studies have found that creatine can protect the brain from neurotoxic agents and certain forms of brain injury . (2650-2652)

7. D-Ribose

A key MItochondrial support supplement

D - ribose is finding utility and acceptance in cardiac surgery ; the heart is one of the organs that respond most favorably to D - ribose supplementation . Supporting the heart’s ability to preserve and rebuild its energy pool by supplementing with D - ribose is one of the first steps in restoring energy efficiency in any cardiovascular condition . Studies have shown it is effective in improving cellular energetics in congestive heart failure , coronary artery disease , and angina (2212-2215)

the best way to quickly replenish D - ribose is to supplement . When administered , a whopping 97 percent ( approximately ) is absorbed into the blood , and eventually moves into tissues without any difficulty (2232-2234)

8. PQQ

Stimulates the growth of Mitochondria

Traditionally, it was believed that generating new mitochondria ( mitochondrial biogenesis ) could only occur as a result of strenuous exercise or extreme calorie restriction, which is why research on PQQ (Pyrroloquinoline Quinone) is so exciting . Early in 2010 , researchers found PQQ not only protected mitochondria from oxidative damage , it also stimulated the growth of new mitochondria ! (2274-2277)

PQQ as a Nootropic

Related to this is cognitive function . As we discussed , the brain uses an incredible amount of energy , and it is utterly dependent on the mitochondria for fuel . A double - blind , randomized , placebo - controlled human clinical trial found that 20 milligrams of oral PQQ taken daily improved short - term memory , attention and concentration , information identification , and processing ability in healthy adults . Effects were greatly enhanced with the addition of CoQ10 supplementation , which makes sense because Complex I transfers its electrons to CoQ10 in the ETC .(2334-2338)

Testing and self-quantification

Self qauntification

Biohacking is shooting in the dark if you don't know what's going on in your body. You might not need to supplement Magnesium or B vitamins. Or something like a Vitamin D deficiency might be the core cause of the Mitochondrial dysfunction that ails you. You don't know until you get blood and hormone tests done. In Ben Greenfield's Biohacking "bible" he itemizes the self-quantification tests which are needed (and how often) to get the full picture of what's going on inside you...

Here’s what the ideal, simple self-quantification scenario would look like:
• DNA test: Once in a lifetime
• Comprehensive blood test: Once per year
• Gut microbiome test or stool panel: Once per year or whenever the gut seems to significantly change in function or health
• DUTCH test: Once per year or when feeling fatigued with no explanation, particularly if libido is low
• Food allergy test such as Cyrex: Once per year or whenever the gut seems to significantly change in function or health
• Readiness and sleep tracking: Daily
• Ketones and glucose testing: Optional, but ideally performed on a daily basis when adopting a new diet or when attempting to evaluate how different food groups affect glycemic variability or ketones
• Micronutrient test: Optional, but to be performed if concerned about energy levels or health issues, or when you want to dial in supplementation and diet protocol even more thoroughly (p. 736)

You likely have problematic gene alleles lurking in your DNA, you really don't know until you get your personal genotyping done and properly interpret your raw genetic data. After a lot of comparison research, Sequencing.com is the service I recommend; their $400 whole genome genetic analysis includes screening for rare genetic diseases and conditions, a detailed longevity report, and access to the Genome Explorer v3, along with a bunch of other cool features and importantly an iron-clad Privacy Forever policy.

Category: Services

Bottom line

Biohacking and changing your health is more complicated than you might imagine, but also more rewarding than you imagine! If biohacking isn't working for you, you're probably underestimating the investment of time, research, and dedication that it takes BUT you're also underestimating how much better life will be on the other side of that investment! 


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