Yet that’s exactly what most AI chatbots dish out.

These large language models scrape the internet, average everything together, and spit back the most common opinions. Common advice leads to common results: metabolic chaos, pills for breakfast, and a slow decline that civilization calls “normal aging.”

You don’t want normal. You want to be uncivilized, strong, vital, and free from the broken system that’s making everyone sick.

The Problem with “Average” Health Info

AI doesn’t think. It averages.

It pulls from forums, studies, guidelines, and blogs, then blends it into something safe, consensus-driven, and popular. Sounds helpful, right? Wrong.

That consensus is built on the same flawed foundations: government dietary guidelines that push processed carbs, pharma-backed research that downplays natural solutions, and a medical system that treats symptoms instead of roots.

Ask an AI about fixing low energy, and it’ll probably tell you to eat whole grains, get moderate exercise, and see your doctor for tests. That’s the advice keeping most men fatigued and dependent.

Studies back this up. Recent tests on top models like GPT-4, Gemini, and others show they often fabricate info, invent fake citations, or bend answers to keep you engaged. One report even caught a high-profile health document loaded with AI-generated phony references.

Worse, these tools are trained on the same censored, biased internet that pushed one-size-fits-all narratives during recent health crises. Distrust the officials? Good instinct. But handing that trust over to an algorithm built on their data is just swapping one leash for another.

You Want Uncommon Results

Average health in America today means multiple prescriptions by middle age, insulin resistance from bad food advice, joint pain from inflammation, and brains fogging up early.

Uncommon health means high energy into your 70s, natural strength without the gym bro supplements, sharp mind, and zero need for the medical merry-go-round.

To get there, you need uncommon knowledge. Stuff that’s been buried, ignored, or labeled “extreme” because it threatens the system.

Things like prioritizing animal foods for real nutrition, ditching seed oils, building muscle with heavy lifts, getting real sun, cold exposure, and rejecting the fear-based mindset that keeps men weak.

AI won’t lead you there reliably. It’s wired for the middle of the road.

Break Free Instead

Stop settling for averaged-out answers that keep you in the herd.

Seek out men who’ve walked the path: read the books that challenge the narrative, listen to the voices big tech tried to silence, experiment on yourself with real food and hard training.

That’s how you become uncivilized.

Strong body, clear mind, independent life.

No algorithms required.

If you’re ready to ditch the average and build real health, start questioning every “expert” consensus, especially when it comes from a machine.

You’ve got the power to fix this. Go get it.

I so desperately did not want write this post about the “sugar diet” this week.

However, having had a number of conversations with people that are seeing pretty incredible success after they damaged their metabolisms through keto/carnivore diets, I think it's only fair to write a post that explores the new trend of eating a high sugar or an even an only sugar diet.

One of the challenges I think that is occurring with this way of eating is that everybody is just kind of regurgitating the same information, which fundamentally comes from a few people.

Anabology

Cole Robinson

Mark Smelly Bell

Durian Rider

Instead of rehashing what everybody's already saying, I wanted to give a small opinion and overview on some of the science on why a high sugar diet might work really well for a person.

As well as digging into a few public specific cases of people who have had success with this, and then also pointing to a number of videos and conversations that are on the internet that I think are really informative.

At Patchwork we help people avoid diet & supplementation mistakes to achieve an optimal metabolism with personalized insights based on your DNA.

We’re getting ready to launch a one of its kind AI powered coach to help you achieve your metabolic health goals. We’re looking for testers! Hit reply or comment below if you’re up for trying.

So what is the sugar diet

There are two core forms of the sugar diet

Sugar Diet (Honey Diet):

Some form of breakfast through til dinner, only eat high sugar based foods. Honey, candy, fruit…no starch.

Then for dinner eat lean meat. Some people add starch, some people add veg, some people add fat.

Sugar Fasting:

Eat only high sugar based foods. That’s it. No meat, no starch, no fat.

You are fasting from everything else.

Why this works

Well first off, you might be thinking. There is no way this will work. For many, it does not. But that is the same with every dietary regimen. We all have different genetics, histories and environments.

FGF-21 (most common reason given)

The most commonly cited reason for this diet working is that by restricting protein and upping foods which put a load on your liver, your body up regulates a hormone called FGF-21.

• FGF21 helps regulate energy expenditure and intake, potentially contributing to body weight management.

• It enhances insulin sensitivity, improves glucose uptake in adipocytes, and can help regulate blood sugar levels.

• FGF21 reduces lipid levels, including triglycerides and low-density lipoprotein (LDL) cholesterol, and increases high-density lipoprotein (HDL) cholesterol.

• FGF21 can increase heat production in tissues, potentially contributing to energy expenditure.

BCAA restriction = insulin sensitivity

Another reason this diet probably works is because we know that large dietary protein loads can cause insulin resistance.

By reducing your protein intake, you are inherently undergoing BCAA restriction and thus reducing drivers of insulin resistance.

I actually think that this is one of the underlying issues with heavy meat or carnivore diets for people who are metabolically compromised.

They end up in a place where they simply can't lose any more weight and they're also struggling with pulling any energy from their existing fat stores.

Their glucose demand of their brain and the elevated stress hormones means that their fasting blood glucose slowly climbs, and I know many carnivores who have a fasting blood glucose in the high 90s.

People with CGMs can do this for themselves and confirm that when you eat sugar by itself, your blood sugar spike is very very acute, but if you eat sugar with me, your blood sugar will remain elevated for hours.

Fat restriction = insulin sensitivity

The diet is fundamentally a low fat and/or a fat restricted diet.

As you get closer to metabolic comprimization dietary fats can drive insulin resistance.

With the CGM example given above, the same goes if you eat sugar with fat. You'll know that if you eat sugar with fat (swamping), your blood sugar will remain elevated for quite a long time.

PUFA’d fat cells are pathologically hyper sensitive to insulin

Something rarely discussed but well explored by Peter, the blogger behind Hyperlipid, is that if you have eaten sufficient amounts of polyunsaturated fats (seed oils) for a long time such that the composition of your fat cells is high in polyunsaturated fats, your fat cells actually become pathologically insulin sensitive.

This means that they are more likely to take up any free fatty acids in your blood and also are more likely to prevent the burning of fat for energy.

This study in formerly obese women showed that “fat oxidation is subnormal”. I will note that dietary saturated fats change this behavior to some degree, and that formerly obese patients is an extreme - but the mechanism is the same for anyone who previously ate a standard american or high PUFA diet.

You can see in this graph above - at rest, during exercise and during recovery the formerly obese patients using much less fat to produce energy than the controls.

“Finally, the really strange thing is” that these formerly obese women have elevated free fatty acids, both at rest and throughout exercise. “If the formerly obese have all this extra lipid available, why don't they oxidise it?”

“Fat burns in the flame of carbohydrate”

Remember our discussion on how we actually make energy?

Well if you look at energy production from the view of the TCA (Krebs) cycle…

There is strong scientific evidence supporting the argument that carbohydrates are essential for efficient fat oxidation by providing oxaloacetate for the TCA cycle.

Glucose tolerance is key in aerobic metabolism, which produces sufficient oxaloacetic acid for the oxidation of acetyl CoA, and at the same time enabling free fatty acids to enter the Krebs cycle.

By being great at burning carbs, you can actually be better at burning fats.

But man thrived on meat 200,000 years ago and no one ever thrived on sugar!

Dr Ken Berry (Carnivore diet personality) actually tried to make this point or an incredibly similar one this week which struck me as a bit odd. Man 200,000 years ago also didn’t have running water or penicillin.

Anyway there is tons of historical precedent for high carbohydrate or even high sugar diets. Albeit - their teeth probably took a huge hit without the modern invention of Nano Hydroxyapatite toothpaste.

Ancient Mesopotamians

The Mesopotamian diet was diverse, with barley as the staple grain for bread and beer. However, dates were a major component, especially in southern regions like Sumer, where date palms were extensively cultivated.

Dates, containing 60-70% sugar, were a staple food, used in cooking, and even served as currency. Honey was also used to preserve fruits and as a sweetener, contributing to a diet with significant natural sugar content.

Archaeological records and texts highlight the economic and dietary importance of dates (Dates in Mesopotamia).

Polynesians

Polynesian societies, including those in Hawaii, Samoa, and Tahiti, consumed a diet rich in starchy crops like taro, yams, and breadfruit, but also included fruits high in natural sugars, such as bananas, coconuts, and sugarcane.

Sugarcane, domesticated in New Guinea around 8000 BC, was chewed for its sweetness and carried during migrations.

These fruits provided a notable sugar component to their diet, complementing their carbohydrate-heavy staples (Polynesian Diet).

Ancient Indians

The ancient Indian diet, particularly during the Indus Valley and Vedic periods, included wheat, barley, rice, and legumes, but also a variety of fruits like mangoes, bananas, and dates.

Sugarcane was cultivated as early as 4000 BC, and by 500 AD, methods to refine sugar were developed.

While refined sugar was likely a luxury, raw sugarcane and fruits contributed natural sugars to the diet, especially in later periods (Ancient Indian Diet).

The results and why this just might stick

The metabolic health space and the weight loss space in general is full of snake oil salesmen.

Every 20-something-year-old influencer has a new weight loss plan or special hack that they want to sell you. What I've come to learn is that you have to pass the fundamental bullshit sniff test for these things to work.

Very simply, when something works, people talk about it. I know this all too well with the work that we do at Patchwork.

And with the numerous people I have come across who make wildly exaggerated claims about them having solved the core reasons of obesity, say with your microbiome - Only to find people on Reddit saying they tried that protocol and it was basically nonsense.

And so here's why I dug into the sugar diet this week.

The reason why this diet I think is hitting a tipping point is because there are actually so many people that are finding that keto/carnivore/fasting/calorie counting trashed their thyroid, messed up their metabolism and they're giving this idea shot and seeing results.

Quite literally - the results speak for themselves.

I've seen many diet gurus have their egos bruised in this space this week as this diet has taken on popularity.

And you'll see more and more people come out against it, but what you have to fundamentally appreciate is that everybody just wants to be lean and not think about food.

It is actually that simple.

That is the base reason why GLP-1s have taken off. You take a weekly injection, and you get lean without thinking about food.

A naturally lean person that is not thinking about food is inherently much healthier.

See for yourself

I am not here to steal the thunder of people that are better health and great outcomes.

One of the things that personally drives me and the work that we do at Patchwork is that people are not believed by those who are supposed to believe them.

We talk to people every single day who go to their doctor with symptoms and issues, and the doctor refuses to do the blood work, prescribe the drug or refer them to the specialist they need.

Hell I did an uncivilized post on what food noise feels like, and a number of people messaged me, basically saying that it was bullshit. Side not - screw you guys.

Here's a list of people I've found to be giving really interesting insights on how they're finding this dietary protocol:

Cole Robinson

Mark Bell

Shark Strong

Joey Andruilli

Emma

Sumgarbomb Emma

The comments on all these videos are like nothing I’ve ever seen before.

In our modern world, obesity and chronic illness have become the norm.

We're told to follow government guidelines, take our medications, and trust the system.

But what if this system is broken? What if the very civilization we've built is what's making us sick?

Today, let's take a look at the weight loss drugs that have been marketed as solutions to our health crises.

From the latest GLP-1 agonists to older amphetamine derivatives, we'll explore how they work, their efficacy, and whether they're truly helping us become healthier or just masking the symptoms of a deeper problem.

What started as just a curiosity and what I thought would be a small post has turned into an absolutely ginormous, comprehensive set of research.

Am I surprised? Not really. In the US, we spend $90B/year trying to lose weight. 45M Americans start a new diet every single year.

That does mean that somehow this post has turned out to be quite the textbook, much like my last one.

The Drugs

Semaglutide (Wegovy, Ozempic)

• History: Developed by Novo Nordisk, approved for diabetes (Ozempic, 2017) and obesity (Wegovy, 2021).

• Mechanism: GLP-1 receptor agonist. Mimics the GLP-1 hormone to increase satiety and slow gastric emptying.

• Efficacy: Approximately 12-15% total body weight loss.

• Cost: $997-$1,850/month.

• Status: Approved for chronic use.

• Adverse Effects: Nausea, vomiting, diarrhea, rare pancreatitis.

Semaglutide is the darling of the weight loss drug world right now, promising significant weight loss with just a weekly injection. But at nearly $2,000 a month (US, Branded, uninsured cost), it's not exactly accessible to everyone. And while it might help you lose weight, is it really addressing the root causes of obesity, or just another quick fix in a society that's addicted to instant gratification?

I've watched several videos of celebrity doctors try to explain how these drugs work. Every single one is different.

There are things that we clearly know - it slows down digestion, it increases satiety in your brain and increases your insulin response.

But there are things that we still don't understand, like why it will reduce impulsive shopping behavior, it reduces alcohol cravings, and increases fertility.

This doesn't cure any of the underlying drivers of obesity or weight gain, and therefore, most people come off it within a year, and most people regain a serious amount of weight after coming off.

Tirzepatide (Zepbound, Mounjaro)

• History: Developed by Eli Lilly, approved for diabetes (Mounjaro, 2022) and obesity (Zepbound, 2023).

• Mechanism: Dual GLP-1 and GIP receptor agonist. Enhances satiety and may boost metabolism.

• Efficacy: Up to 18-21% body weight loss.

• Cost: Approximately $1,000-$1,500/month.

• Status: Approved for chronic use.

• Adverse Effects: Gastrointestinal upset, rare thyroid tumors, pancreatitis.

Tirzepatide is even more effective than Semaglutide, with some patients losing up to 21% of their body weight.

It has similar unknowns to Semaglutide, but Is known for having less side effects.

Liraglutide (Saxenda)

• History: Novo Nordisk, approved for diabetes (Victoza, 2010) and obesity (Saxenda, 2014).

• Mechanism: GLP-1 receptor agonist. Increases satiety and slows gastric emptying.

• Efficacy: Approximately 4-6% weight loss.

• Cost: Approximately $1,300/month.

• Status: Approved for chronic use.

• Adverse Effects: Nausea, vomiting, pancreatitis.

Liraglutide has been around longer and is less effective than its newer counterparts. With only 4-6% weight loss, it's hard to justify the cost and side effects for many people.

Phentermine/Topiramate (Qsymia)

• History: Vivus, approved 2012.

• Mechanism: Phentermine suppresses appetite; Topiramate reduces food cravings.

• Efficacy: 8-10% weight loss.

• Cost: Approximately $100-$200/month.

• Status: Approved for chronic use.

• Adverse Effects: Insomnia, cognitive effects, dry mouth, teratogenicity.

Qsymia combines two drugs to achieve moderate weight loss. It's cheaper than the GLP-1 agonists, but the side effects, especially cognitive issues, might not be worth it for some.

Naltrexone/Bupropion (Contrave)

• History: Orexigen, approved 2014.

• Mechanism: Bupropion reduces cravings; Naltrexone reduces reward-driven eating.

• Efficacy: Approximately 5% weight loss.

• Cost: Approximately $99/month.

• Status: Approved for chronic use.

• Adverse Effects: Nausea, headache, increased blood pressure, risk of seizures.

With only 5% weight loss, Contrave is one of the least effective options. Its affordability is a plus, but the side effects, including seizure risk, are concerning.

Despite the efficacy during treatment, there is a notable gap in published research specifically addressing weight regain after discontinuing naltrexone for weight loss.

The American Academy of Family Physicians (AAFP) noted in 2015 that "it is unknown if weight gain occurs after stopping the medication," indicating a lack of long-term follow-up data at that time.

Orlistat (Xenical, Alli)

• History: Roche (Xenical, 1999), GSK (Alli, OTC, 2007).

• Mechanism: Lipase inhibitor; blocks fat absorption.

• Efficacy: 3-5% weight loss.

• Cost: $30-$60/month (OTC).

• Status: Approved for chronic use.

• Adverse Effects: Oily stools, diarrhea, fat-soluble vitamin deficiency.

Orlistat is available over the counter and is relatively cheap, but its side effects are notoriously unpleasant, and the weight loss is minimal.

If you block fat absorption in your body, it comes out in your poop, and this one is renowned for making people leak poop into their underwear.

Phentermine (Adipex-P, Lomaira)

• History: Approved 1959, oldest prescription weight loss drug.

• Mechanism: Sympathomimetic amine; suppresses appetite.

• Efficacy: 5-10% weight loss (short-term use).

• Cost: $20-$50/month.

• Status: Approved for short-term use.

• Adverse Effects: Insomnia, hypertension, tachycardia, abuse potential.

Phentermine is dirt cheap and has been around for decades, but it's only approved for short-term use due to its side effects and abuse potential.

I have read some conspiracy theories around how it was flagged for pulling and how faulty the studies were that said it was unhealthy.

Diethylpropion (Tenuate)

• History: Approved 1959, similar to phentermine.

• Mechanism: Sympathomimetic amine; suppresses appetite.

• Efficacy: Approximately 10% weight loss (short-term use).

• Cost: Varies.

• Status: Approved for short-term use.

• Adverse Effects: Similar to phentermine.

Diethylpropion is another old-school appetite suppressant, offering decent short-term results but with the same risks as Phentermine.

Benzphetamine (Didrex, Regimex)

• History: Approved 1960s, amphetamine derivative.

• Mechanism: Sympathomimetic amine; suppresses appetite.

• Efficacy: Approximately 5-10% weight loss (short-term use).

• Cost: Varies.

• Status: Approved for short-term use.

• Adverse Effects: Similar to phentermine.

Benzphetamine is less commonly used but follows the same pattern as other amphetamine derivatives: moderate efficacy with significant risks.

Phendimetrazine (Bontril, Melfiat)

• History: Approved 1959, amphetamine derivative.

• Mechanism: Sympathomimetic amine; suppresses appetite.

• Efficacy: Approximately 5-10% weight loss (short-term use).

• Cost: Varies.

• Status: Approved for short-term use.

• Adverse Effects: Similar to phentermine.

Phendimetrazine is another in the long line of amphetamine-like drugs, with similar benefits and drawbacks.

Methamphetamine (Desoxyn)

• History: Approved for ADHD, also for short-term obesity treatment.

• Mechanism: Potent CNS stimulant; suppresses appetite, increases metabolism.

• Efficacy: Approximately 5-10% weight loss (short-term use).

• Cost: Varies.

• Status: Approved for short-term use, rarely prescribed due to abuse risk.

• Adverse Effects: High abuse risk, cardiovascular and psychiatric effects.

Methamphetamine for weight loss? In what world is this a good idea? The risks far outweigh any potential benefits.

Lorcaserin (Belviq, withdrawn)

• History: Eisai, approved 2012, withdrawn 2020 (cancer risk).

• Mechanism: 5-HT2C serotonin receptor agonist; increases satiety.

• Efficacy: Approximately 3-4% weight loss.

• Status: Withdrawn.

• Adverse Effects: Headache, dizziness, increased cancer risk.

Lorcaserin's withdrawal due to cancer risk highlights the potential dangers of these drugs, even after initial approval.

Sibutramine (Meridia, withdrawn)

• History: Abbott, approved 1997, withdrawn 2010 (cardiovascular risk).

• Mechanism: Serotonin-norepinephrine reuptake inhibitor; increases satiety, slightly increases metabolism.

• Efficacy: Approximately 5% weight loss.

• Status: Withdrawn.

• Adverse Effects: Hypertension, heart attack, stroke.

Sibutramine's cardiovascular risks led to its withdrawal, a reminder that weight loss drugs can have serious consequences.

Rimonabant (Acomplia, withdrawn)

• History: Sanofi, approved in Europe 2006, withdrawn 2008 (psychiatric risk).

• Mechanism: CB1 cannabinoid receptor antagonist; reduces appetite and cravings.

• Efficacy: Approximately 5% weight loss.

• Status: Withdrawn.

• Adverse Effects: Severe depression, suicide risk.

Rimonabant's psychiatric side effects were severe enough to pull it from the market, underscoring the mental health risks of some weight loss drugs.

Interestingly enough, if you dig into the psychiatric effects, Rimonabant is actually safer than gastric bypass. The mechanism by which this works is directly opposite to the way in which seed oils drive hunger, obesity, and cravings.

There are CB1 receptors in your brain and in your gut. When you can target the ones in your gut, you're gonna have a good time. When you target the ones in your brain, you're gonna have a bad time, which is what happened here.

In the next decade, we will see drugs that target CB1 receptors in the gut only come to market.

Setmelanotide (Imcivree)

• History: For rare genetic obesity syndromes only.

• Mechanism: MC4R agonist; increases satiety.

• Manufacturer: Rhythm Pharmaceuticals.

• Efficacy: Significant in rare disorders.

• Status: Approved for rare genetic obesity.

• Adverse Effects: Injection site reactions, hyperpigmentation.

Setmelanotide is a niche drug, effective for specific genetic conditions but not broadly applicable.

Plenity (Gelesis100)

• History: FDA approved 2019.

• Mechanism: Oral hydrogel expands in stomach to promote fullness.

• Efficacy: Approximately 2-3% weight loss.

• Status: Approved for chronic use.

• Adverse Effects: Bloating, gastrointestinal discomfort.

Plenity's non-pharmacological approach is intriguing, but its minimal efficacy limits its impact.

Effectively stuffing your stomach can be done by other supplements & food too. Doesn’t solve any underlying issues.

Pramlintide (Symlin)

• History: Approved for diabetes, studied for obesity.

• Mechanism: Amylin analog; increases satiety by slowing gastric emptying.

• Efficacy: Approximately 3-6% weight loss.

• Status: Not FDA-approved for obesity alone.

• Adverse Effects: Nausea.

Pramlintide's use for weight loss is off-label, with modest results and limited approval.

Metformin (Glucophage)

• History: Approved for diabetes, used off-label for weight loss.

• Mechanism: Increases insulin sensitivity, may increase satiety via GLP-1.

• Efficacy: Approximately 2-3% weight loss.

• Status: Not FDA-approved for obesity alone.

• Adverse Effects: Gastrointestinal upset, rare lactic acidosis.

Metformin is a common off-label choice, but its weight loss effects are minimal.

Thyroid Hormones (Levothyroxine, T3, NDT)

• History: Used for hypothyroidism; sometimes abused for weight loss.

• Mechanism: Increases basal metabolic rate.

• Efficacy: Only effective in hypothyroid patients; dangerous in euthyroid.

• Status: Not approved for obesity.

• Adverse Effects: Arrhythmia, osteoporosis, muscle loss.

Using thyroid hormones for weight loss in healthy individuals is a risky and unapproved practice, although before any real weight loss drugs came to market it was prescribed for weight loss - typically confirming that rare weight gain was driven by hypothyroidism back in the day.

Experimental Compounds

Adipotide

Adipotide (also known as FTPP or Prohibitin-TP01) is a synthetic peptide that targets blood vessels supplying white adipose tissue, causing selective apoptosis (cell death) of fat cells by cutting off their blood supply. This leads to fat loss and improved metabolic markers.

• In obese rhesus monkeys, daily subcutaneous injections of Adipotide resulted in significant, dose-dependent weight loss: up to 20% reduction in body weight, 17% reduction in BMI, and 14% reduction in abdominal circumference over several weeks

• Fat loss was confirmed by DEXA and MRI scans, with up to 39% decrease in fat deposits. Improvements in insulin resistance and metabolic health were also observed.

• Human trials have been put on hold as the drug destroys fat cells indiscriminately It appears that in humans, that includes attacking the fat in kidneys and damaging kidneys and also attacking the fat in their brains.

• Oddly, this is still sold by experimental peptide companies on the internet. Reddit users have noted that they literally feel like their brains are rotting when they use it.

Retarutide

Retatrutide is a novel “triple agonist” that activates GLP-1, GIP, and glucagon receptors.

This combination reduces appetite, improves glucose metabolism, and increases energy expenditure, making it more comprehensive than previous drugs like semaglutide or tirzepatide.

In phase 2 clinical trials, participants lost up to 24.2% of their body weight after 48 weeks of weekly injections-among the highest results for any obesity drug to date.

Most side effects are mild and gastrointestinal (nausea, diarrhea).

You can buy this again online quite cheaply from experimental peptide companies.

Users who switch to this from Ozempic report that the side effects they experience are way lower.

I would expect that on a long enough timeline, we'll see users that come off of this drug rebound the weight gain as it doesn't solve any underlying issues.

MOTS-C

MOTS-C is a mitochondrial-derived peptide that acts as an “exercise mimetic,” improving mitochondrial function, enhancing fatty acid metabolism, and increasing insulin sensitivity.

It was originally discovered when they were trying to find a peptide to give to elderly patients who moved into care homes and experienced sarcopenia.

It is being explored for its ability to prevent obesity, improve glucose regulation, and reduce inflammation.

In animal studies, MOTS-C prevented diet-induced obesity, reduced fat accumulation, and improved insulin sensitivity, especially in high-fat diet conditions.

Animal studies suggest a good safety profile, with benefits for metabolic health and no reported major adverse effects. More human data is needed.

Available from experimental peptide companies as an injection & nasal spray

DNP

DNP is a chemical that uncouples oxidative phosphorylation in mitochondria, causing the body to burn more energy as heat instead of storing it as fat. This dramatically increases metabolic rate and calorie burning

DNP can cause rapid weight loss (up to 1.5 kg per week) by increasing basal metabolic rate by 30–40%

DNP is extremely dangerous and potentially lethal. Side effects include uncontrolled hyperthermia (dangerously high body temperature), tachycardia, diaphoresis, and risk of death

The drug has a very narrow therapeutic window, and even small overdoses can be fatal. It was banned for human use in the 1930s after numerous deaths and cases of blindness due to cataracts.

DNP is not approved for weight loss and is considered unfit for human consumption by regulatory agencies worldwide.

Whilst I think that increasing metabolic rate should be the goal weight loss meds aspire to, DNP is acutely toxic to human mitochondria which totally defeats the point.

Supplements

Calocurb

Calocurb is a natural, plant-based appetite suppressant designed to support weight management by helping users feel full faster and reduce cravings. Its active ingredient is Amarasate®, a patented extract from New Zealand-grown bitter hops.

Calocurb works by stimulating the release of GLP-1, CCK, and PYY-gut hormones that signal satiety to the brain-helping reduce hunger by 30%, cravings by 40%, and calorie intake by 18% within an hour of use, according to clinical trials.

The reason I even know about this one is because Ben Greenfield seems to promote it all the time on his podcast. And that's where it's almost a bit uneasy because I generally find with anything in the weight loss space if it actually works, it will pass a bullshit detector. By that, I mean people will be posting about it on Reddit etc.

The amazon reviews aren’t great and it’s kinda expensive at $80 for about a 20 day supply.

Glucomannan

Glucomannan is a water-soluble dietary fiber derived from the root of the konjac plant. It is often used as a weight loss supplement due to its ability to absorb water and expand in the stomach, promoting a feeling of fullness and reducing calorie intake.

One study found no significant difference in weight loss compared to placebo after eight weeks, though other studies report small reductions in body weight (about 1.5–2.2 kg over several weeks).

Minor side effects: bloating, diarrhea, flatulence, abdominal discomfort.

Back to basics with this one - fill up your stomach = eat less
It’s $17 for 180 capsules and the Amazon reviews are much more positive.

T2 Thyroid

T2 is a naturally occurring thyroid hormone metabolite, distinct from the more commonly prescribed T4 (thyroxine) and T3 (triiodothyronine). T2 is gaining attention for its potential to boost metabolism and aid weight loss, particularly in thyroid patients.

• Increases basal metabolic rate by enhancing mitochondrial activity, leading to higher energy expenditure at rest.

• Promotes the browning of white fat, increasing thermogenesis and fat burning.

• Limited human data: One study reported a 4% reduction in body weight over several weeks in people with normal thyroid function.

• T2 is available over the counter in some supplement forms, unlike T3 and T4, which require a prescription.

• Popular in bodybuilding circles because it doesn’t suppress T3 or T4

Like calocurb - I’m a bit meh on this. Where are the raving fans?

I know a few people who have tried DNP (idiots) but no one who has tried T2.

Physical and Surgical Interventions

Sleeve Gastrectomy

• Mechanism: Removes 80% of stomach, reduces ghrelin, increases satiety.

• Efficacy: 20-25% total body weight loss.

• Risks: Leak, reflux, nutrient deficiency.

Sleeve gastrectomy is highly effective but invasive, with lifelong nutritional implications. Many users report initial rapid weight loss, followed by weight regain. It’s almost as if losing weight by restricting calories permanently doesn’t work?

Roux-en-Y Gastric Bypass

• Mechanism: Small stomach pouch, bypasses part of intestine; increases satiety and alters metabolism.

• Efficacy: 25-35% total body weight loss.

• Risks: Dumping syndrome, ulcers, malabsorption.

Gastric bypass offers dramatic results but comes with significant risks and lifestyle changes.
Interestingly enough this works similar to Rimonabant in that food is directed around your CB1 receptors and as such patients see the same benefits.

Biliopancreatic Diversion with Duodenal Switch

• Mechanism: Combines sleeve and intestinal bypass; strong effect on satiety and metabolism.

• Efficacy: 30-40% total body weight loss.

• Risks: Severe malnutrition, diarrhea.

This procedure is the most effective but also the most risky, with severe potential complications.

Adjustable Gastric Banding

• Mechanism: Band restricts stomach size, increases satiety.

• Efficacy: 10-20% total body weight loss.

• Risks: Band slippage, erosion, less effective long-term.

Gastric banding is less invasive but has fallen out of favor due to lower long-term efficacy.

ObeEnd (Wristband)

• Mechanism: Neuromodulation to reduce appetite; claims to increase brown fat.

• Efficacy: Modest (4-8% reported).

• Risks: Skin irritation, unproven long-term safety.

The wristband's claims are intriguing but lack robust evidence, making it a questionable option.

Quite honestly I was shocked that I had never heard of this when I found the website advertising the product. In fact, I actually emailed them to ask them if what they were selling was real. No response so far.

It's effectively a Fitbit with a little electrode that shocks you into not being hungry.

Conclusion

As we've seen, there's no shortage of weight loss drugs and interventions on the market, each with its own promises and pitfalls. From expensive injections that mimic hormones to surgical procedures that alter our digestive systems, these solutions reflect our obsession with quick fixes and technological interventions and that the market is willing to respond.

But are they truly making us healthier, or are they just symptoms of a deeper malaise?

Perhaps it's time to question whether these "solutions" are part of the problem.

Maybe, just maybe, the path to true health lies not in more civilization, but in becoming a little more uncivilized, returning to natural rhythms, eating whole foods, moving our bodies as nature intended, and listening to our innate wisdom rather than relying on pills and procedures.

After all, if civilization is making us sick, maybe it's time to become uncivilized.

Earlier this week, I found myself getting my tongue twisted trying to explain how a human actually makes energy from food.

Something something carbohydrate. Something something mitochondria. Something something electron transport chain.

And so I decided I would fully learn and understand how a human makes energy, including all of the steps and the additional pieces that are needed to get it from one step to another.

You see, if you didn't already know, when we produce energy from food, it doesn't just naturally go along a process.

We need things called cofactors to take it from one process to the next. And many times people are deficient in these cofactors and thus they can't produce energy productively.

Anyway, my goal with this post is to give you a thorough explanation of how a human takes food and turns it into actionable energy that they use to move, think, breathe, and exist.

Table of Contents

Step 1: Macronutrients & Digestion

Step 2: Into the Blood

Step 3: Into the Cells & Further Processing

Step 4: Onto the Powerhouse! Getting into the Mitochondria and Ready to Make Energy

Step 5: The TCA Cycle (Also called the Krebs Cycle or Citric Acid Cycle)

Fun fact - 99% of doctors don’t know you can actually test for leaks in someone’s TCA cycle.

Step 6: The Electron Transport Chain (ETC)

Bonus parts: Ketones & Methylene Blue

Conclusion

At Patchwork we help people avoid diet & supplementation mistakes to achieve an optimal metabolism with personalized insights based on your DNA.

Not sure if we’re a good fit? Take the quiz

Step 1: Macronutrients & Digestion

Energy in your body comes from the food you eat, which gets broken down into tiny parts to make a special energy battery called ATP.

Think of ATP like a rechargeable battery that powers everything from running to blinking!

Here’s how it works, your body uses three main types of food:

• Carbohydrates like bread or fruits break into sugars like glucose & fructose

  • This is done in the mouth & intestines by an enzyme called Amylase

• Fats like butter or oils break into fatty acids like stearic acid (which we like) and linoleic acid (which we don’t like)

  • This is done in the stomach & intestines by an enzyme called Lipase

  • You need bile to emulsify the fats which will make them accessible to lipases

  • You also need calcium to digest phospholipids

• Proteins like chicken break into individual amino acids (and peptides) such as glycine or valine

  • Hydrochloric acid (stomach acid) unfolds proteins so that they can be broken up

  • This is done in the stomach & intestines by a protease enzymes and pancreatic enzymes

  • Zinc and Calcium are essential in this enzyme function

Step 2: Into the Blood

You can almost think that until food is absorbed in to the bloodstream, it is essentially still outside of your body. You can’t access it.

Here’s how we gain access to each piece:

• Simple sugars like glucose are absorbed straight into the bloodstream

• Fatty acids and monoglycerides are absorbed by intestinal cells and reassembled into triglycerides, which are then packaged into chylomicrons for transport in the bloodstream

• Amino Acids move from the gut into the cells and then transported across the basolateral membrane into the bloodstream

  • Sodium (salt) is often used as a co-transporter

Step 3: Into the Cells & Further Processing

Okay, so we have our food that's broken down into these tiny pieces and it's running through our body in the blood. Now we need to get it into our cells, and after that, will be how we get it into the mitochondria.

• Glucose enters cells using proteins called GLUT transporters (like GLUT1, GLUT2, GLUT4, etc.)

  • These transporters act like gates in the cell membrane. When glucose binds to the transporter, it changes shape and moves glucose from outside to inside the cell

  • Insulin (a hormone ketoers are afraid of) signals these cells to put more GLUT4 transporters on their surface, letting more glucose in after you eat

  • In your kidneys and intestines there is also a SGLT transporter which behaves the same way but requires sodium

  • Inside of the cell glucose is taken through a number of steps some of which are called glycolysis ultimately producing pyruvate

    • Glycolysis uses magnesium and NAD+

• Fructose enters cells using specific transport proteins called GLUT5/GLUT2

  • This mainly happens in the liver

  • In the liver, fructose goes through a number of processing steps that require ATP (base unit of energy we’re trying to create) to get it into something called pyruvate

  • Excess fructose is turned into triglycerides (fat) in the liver

    • Triglycerides are packaged up as VLDL and sent into the bloodstream

      • This step requires choline

      • Most people are choline deficient

• Chylomicrons & VLDL encounter another enzyme called lipoprotein lipase (LPL) when they reach muscle or fat cells which breaks them down into free fatty acids and glycerol

  • The free fatty acids released by LPL can now cross the cell membrane and this uptake is facilitated by fatty acid transport proteins

  • Long Chain free fatty acids inside the cell are “activated” to form fatty acyl-CoA

    • This step requires ATP (base unit of energy we’re trying to create) and Coenzyme A

  • Short Chain free fatty acids don’t require activation

• Amino acids enter cells through specialized proteins in the cell membrane called amino acid transporters (just like glucose or fructose)

  • Some amino acid transporters use sodium, potassium or chloride to do their job

Step 4: Onto the Powerhouse! Getting into the Mitochondria and Ready to Make Energy

Funny story - I was under the impression until about 2 years ago, that mitochondria were theoretical parts of a cell that we’ve actually never seen - in the same way that physicists have theoretical particles.

I discovered quite publicly that no this isn’t theory. We have pictures of them. They are real - on Tucker Goodrich’s podcast

Okay so we have the pieces we need inside the cell. Inside the cell is also the mitochondria. We need to get these pieces into the mitochondria so that they can make energy.

Here’s how we get them in:

• Pyruvate (from carbs) is taken into the mitochondria via a specialized protein

• Fatty acyl-CoA forms fatty acyl-carnitine using carnitine which obtained from diet or synthesized in the body

  • Most people are carnitine deficient

• Short chain fatty acids cross the mitochondrial membranes directly-they do not require the carnitine shuttle or any specific transporter

  • This is why MCT oil or Coconut oil can be so powerful

  • Once inside the mitochondria they are activated to acyl-CoA using ATP and Coenzyme A

• Amino acids can pass through the outer mitochondrial barrier without much restriction. The inner membrane is highly selective and impermeable to most small molecules, including amino acids. Specialized transporter proteins are required for amino acids to enter the mitochondrial matrix.

Here’s how we prep them for energy production:

• Pyruvate is converted to acetyl-CoA by the pyruvate dehydrogenase complex

  • This requires Coenzyme A, Vitamin B1 (Thiamine), Lipoic Acid, Vitamin B2 and NAD+ (which comes from Vitamin B3)

• Fatty acyl-CoA undergoes beta-oxidation to generate acetyl-CoA, NADH, and FADH₂

• Amino acids are converted into acetyl-CoA and other TCA cycle intermediates (more on the TCA cycle later) via several different processes

  • This requires Vitamin B1, B2, B3, B5, B6, B7, B9, B12

Step 5: The TCA Cycle (Also called the Krebs Cycle or Citric Acid Cycle)

The TCA cycle (also called the Krebs cycle or citric acid cycle) is the main way your body turns food derivates into usable energy.

The main input as you might have noticed above is a molecule called acetyl-CoA.

The Main Steps:

1. Acetyl-CoA (2 carbons) joins oxaloacetate (4 carbons) to make citrate (6 carbons).

2. Citrate is rearranged and chopped up, releasing two carbon atoms as carbon dioxide (CO₂)-that’s the waste you breathe out.

3. As the cycle continues, the original oxaloacetate is re-formed, ready to start the cycle again with a new acetyl-CoA.

What Comes Out?

For each turn of the cycle, you get:

• 3 NADH (an “energy carrier” molecule)

• 1 FADH₂ (another energy carrier)

• 1 GTP or ATP (the cell’s direct energy currency)

• 2 CO₂

Why Is It Important?

• NADH and FADH₂ carry high-energy electrons to the electron transport chain (another part of the mitochondria), where most ATP (energy) is made.

  • We explore the electron transport chain below

• The TCA cycle is a “hub” for metabolism: it connects the breakdown product of carbs, fats, and proteins, (acetyl-CoA) and provides building blocks for other molecules your body needs

The TCA cycle is a repeating loop that turns the food you eat into energy your body can use.

It’s essential for life. If it stops, cells can’t make enough energy to survive.

The cycle itself requires a bunch of additional cofactors to run. Coenzyme A, Vitamin B1 (Thiamine), Lipoic Acid, NAD+ (which comes from Vitamin B3), Magnesium and Calcium.

Furthermore - if steps break or slow down due to external factors additional nutrients may be needed to plug the leak/fix the slow down. That is step dependent. The majority of people have inborn errors in the TCA cycle given our mishmash of genetics and the aggressive environment we now deal with.

Fun fact - 99% of doctors don’t know you can actually test for leaks in someone’s TCA cycle.

Patchwork is building rapid testing, interpretation and protocols to address someones energy production issues in the TCA cycle using something called an Organic Acids Test. You can join the waitlist here.

Use the invite code: Uncivilized to get a $100 discount on launch

Step 6: The Electron Transport Chain (ETC)

First off, if you've made it this far, congratulations to you. This gets more and more complex the further down you go and I've never really been able to put it all together until I wrote this post.

From step 5 we saw the critical output of each turn of the TCA cycle is 3 NADH and 1 FADH₂ molecule. These guys really make the energy that powers life.

The ETC uses high-energy electrons carried by NADH and FADH₂.

How does it work?

1. Electrons are dropped off:

   1. NADH and FADH₂ deliver their electrons to the first protein complexes in the chain.

2. Electrons move down the chain:

   1. The electrons are passed along a series of four big protein complexes (I, II, III, IV) and small carriers (like ubiquinone and cytochrome c).

3. Proton pumping:

   1. As electrons travel through the complexes, energy is used to pump protons (H⁺ ions) from inside the mitochondria (the matrix) to the space between the membranes (the intermembrane space). This builds up a high concentration of protons outside the inner membrane.

4. Oxygen is the final electron acceptor:

   1. At the end of the chain, the electrons combine with oxygen (which you breathe in) and protons to make water. Without oxygen, the chain stops.

5. ATP is made:

   1. The protons want to flow back into the matrix (like water behind a dam). They rush through a special protein called ATP synthase, which uses this flow to make ATP from ADP-just like a water wheel making electricity

Each of the protein complexes has it’s own nutrient need but the critical cofactor that makes the ETC work is CoQ10 which carries electrons and protons up and down the chain.

Bonus parts: Ketones & Methylene Blue

Even in ketosis, the majority of the fuel that your body is burning is fatty acids, which we've already explained goes through fatty acid oxidation and then its own part of the TCA cycle. However, I want to mention how ketones work and also what methylene blue does in the context of how we make energy.

Ketones

Ketone bodies (mainly β-hydroxybutyrate and acetoacetate) are produced in the liver and transported to other tissues (like brain, heart, and muscle) during fasting, low-carb diets, or prolonged exercise.

Ketone bodies (acetoacetate and β-hydroxybutyrate) are small, water-soluble molecules produced in the liver mitochondria from fatty acids. Once made, they diffuse out of liver cells into the blood and are transported to other tissues (like brain, heart, and muscle)

When these tissues use ketones for energy, ketone bodies enter cells and cross the mitochondrial membranes without the need for carnitine.

In these tissues, ketones are converted into our old friend acetyl-CoA - And thus the story begins again as they enter the TCA cycle to produce energy.

Methylene Blue (MB)

Used by many bio-hackers and recently as part of the conversation now that the new HHS secretary was spotted taking this on a plane. Methylene Blue can act as a back up generator in energy production.

• Bypassing Damaged Complexes

  • Normal ETC Flow: Electrons from NADH and FADH₂ travel through complexes I → III → IV, creating a proton gradient to make ATP.

  • Methylene Blue’s Role: If Complex I is damaged (e.g., in neurodegenerative diseases), MB accepts electrons directly from NADH and shuttles them to cytochrome c (bypassing Complex I). This keeps the ETC running smoothly.

• Enhancing Complex IV Activity

  • MB donates electrons to Complex IV (cytochrome c oxidase), boosting its activity. This increases oxygen consumption and ATP production.

  • Example: In Alzheimer’s or Parkinson’s, where mitochondrial function declines, MB helps neurons maintain energy levels

• Reducing Harmful Byproducts

  • Less Electron Leakage: By providing a direct path for electrons, MB minimizes “leaky” electrons that form reactive oxygen species (ROS) like superoxide radicals. Fewer ROS means less oxidative damage to cells.

• Supporting Energy in Stressful Conditions

  • Cancer Cells: Tumors rely on inefficient glycolysis (Warburg effect). MB forces them back to oxidative phosphorylation, slowing growth.

  • Chronic Fatigue: MB improves ATP production in energy-starved cells, alleviating fatigue

Conclusion

Well, congratulations. You made it to graduation. If you read and understood any of this, I give you a B+.

Fundamentally, what I wanted to do in this post is explain that it's actually not that complex how we make energy.

There are a bunch of additional co-factors involved when we talk about vitamins and why we need to take them or choline and why we need to make sure we're getting enough.

It's important because we actually do need those things in making energy.

Oh there’s the bell… Class dismissed.

Our story today begins somewhere close to where we left off last week in looking at human metabolisms that have been significantly suppressed and what we might do about it.

Having a significantly suppressed or efficient metabolism, to me, holds the key to why some easily lose weight on a diet vs many that don’t. Why some get hypervitaminosis or some toxicity vs not. And why, despite society telling them they are lying, many suffering with weight issues cannot seem to lose weight whilst white knuckling through a 1000kcal/day diet.

After last week’s post and in looking at where my own metabolism should be vs where it actually is I started to dig into the questions:

What can one do about it?
How do we carry out metabolic repair?
Can you increase your metabolism?

Amongst the science and research which might hold the answer to these questions the little known story of Billy Craig and his 6000kcal/day diet came up.

Billy hasn’t made it easy to piece together his story.

One minor podcast appearance, a self published book with a single 3 star review (which I finished this morning), a sporadically updated patreon, a few forum mentions and a site with several 404 links is most of what is available on the story.

I read through it all.

His original diet experiment ran from 2004 - 2006, and his self published book was released 12 years later in 2018 which definitely added to the complexity of the collage I’ve tried to put together here.

In this post I’ll go through the best explanation of his story, some fascinating insights from his book and how I think it all fits in the context of the current metabolic crisis we all face.

I’ve reached out to Billy and hope to get him on the Patchwork podcast soon!

The 6000kcal Diet Experiment

Background and Context

Billy Craig is an independent researcher with a Masters in Psychology whose work focuses on the psychology of dieting behaviors and the metabolic effects of energy intake.

His research challenges traditional dieting culture, which often emphasizes calorie restriction and increased physical activity.

Instead, Craig advocates for consistent eating patterns, suggesting that the body performs better with stable, reliable energy supply. This philosophy is detailed in his science heavy book, Consistent Eating: Is Dieting Harming Your Health And Your Weight Loss?, where he explores how restrictive diets can lead to compensatory behaviors and metabolic slowdowns.

Billy's interest in high calorie intake stems from his belief that the thyroid gland, which regulates metabolism, functions optimally with consistent energy availability.

This led him to conduct a personal experiment on the back of a disagreement to test whether increasing calorie intake could enhance metabolic function, potentially leading to weight loss without restriction.

Before being deep in independent research Billy was an professional mountain biker and then a personal trainer which is where this all began.

Sometime around the end of 2003/ beginning of 2004 it appears that Billy had a disagreement with a trainer in his gym as to the advice they were giving clients in order to get them to lose weight.

He’d heard “Eat less, move more” one too many times it seems. Taking your total energy expenditure, subtracting 500kcal from it and expecting to lose 1lb of fat a week (3500kcal) from energy restriction seemed not only banal but simply unsuccessful both in the short term and long term.

And so from what I can piece together, Billy set to prove his gym wrong by trying to increase his metabolic rate through adaptation (not moving more) such that a high metabolic rate would naturally erode adipose tissue given it’s demand for consistent energy.

Methodology and Timeline

From 2004 to 2006, Billy conducted a self-experiment where he gradually increased his daily calorie intake. The experiment progressed as follows:

• Initial Intake: Started at 3500 calories per day, ignoring advice to reduce by 500 calories, based on his understanding of thyroid function and metabolic regulation.

• Structure of Intake: In trying to keep energy stable, Billy apportioned his food intake equally across all of the hours of the day to the smallest breaks possible. No forced fasting, no big meals. Similar amount of food every few hours.

• Progression: He increased linearly to 4500 calories until weight stable, then increased linearly again until ultimately reached 6000 calories per day.

• Duration: The experiment spanned approximately two years, with measurements taken at various stages.

• Exercise Levels: Remained consistent, as Craig was teaching spin classes and competing in sports, providing a stable physical activity baseline.

The experiment aimed to test the hypothesis that consistent high calorie intake could increase metabolic rate, allowing the body to burn more calories and potentially reduce fat stores without the need for calorie restriction.

To achieve the high calorie intake, particularly at 6000 calories, Billy ended up relying on candy for ease of counting, carrying, and palatability which is an important detail for understanding the practical implementation and somewhat defies what we know about PUFAs and their role in metabolic suppression both at the tissue level and in the thyroid.

Observed Outcomes and Physiological Changes

During the experiment, Billy observed several physiological changes, which are detailed in his blog post, Kellogg Passion Killer and 6000 kcal per day.

These include:

• Increased Body Temperature: His body temperature rose, which is often associated with an elevated metabolic rate, suggesting his body was adapting to burn more energy.

• No Fatigue: Despite the high calorie intake, he reported no fatigue, indicating efficient energy utilization and possibly improved metabolic efficiency.

• Dramatic Fat Loss: Unexpectedly, his fat levels decreased significantly, even though he was consuming a large calorie “surplus”. This aligns with his premise that the body can adapt to burn excess calories when consistently provided with energy.

• Metabolic Adaptation: His resting metabolic rate (RMR) increased to match the intake, as measured by his boss during the experiment. This supports the idea that the thyroid and metabolic systems can adjust to higher energy demands when consistently fueled.

These outcomes suggest that, for Billy, the high and consistent calorie intake led to a hypermetabolic state, in which he had made his thyroid more active.

As explored in his book - a hypermetabolic state is a luxury of abundance where your metabolism is fundamentally inefficient. You have enough energy to do any and all metabolic processes and then you just rid yourself of the excess through heat. Something we consistently see in newborns.

Challenges and Limitations

While the experiment yielded interesting results, it also highlighted several challenges:

• Dependency on Constant Feeding: At 6000 calories, Billy struggled to go without food for more than an hour, indicating a high dependency on constant energy supply. The hypermetabolic state whilst slow to build to, was like a runaway train.
  
  This is detailed in his Patreon Q&A, What Would Billy Say? June 2018 Q&A, where he mentioned structured meal times, including having to wake up in the middle of the night to eat, to maintain the intake.

• Use of Junk Foods: To meet the calorie goals, especially at such high levels, he relied on junk food (candy). This is a practical consideration but raises concerns about nutritional quality, as these foods lack essential nutrients, are full of life destroying Omega-6 fats and could pose long-term health risks.
  
  Although this does lend clues to how seed oils become more dangerous when we have slower metabolisms, and how high metabolisms can protect against them.

• Discomfort at High Intake: A discussion on the Low Toxin Forum notes that Billy mentioned the experiment becoming uncomfortable, with him unable to sit still at the end.
  
  We categorically know that in a metabolically suppressed state, Non-Exercise Activity Thermogenesis (NEAT) is drastically ramped down so it would make sense in a hypermetabolic state, the alternative would happen. You become that high energy kid that can’t sit still.
  
  Even as an adult I know people like this.

Billy noted that being at either end of the metabolic spectrum (very low or very high calorie intake) comes with health risks. He concluded that for him, the ideal range was between 3200 and 3600 calories per day, back where he started and in his podcast appearance stated that, that is where he like to stay now.

Broader Implications and Controversy

Billy's experiment fundamentally challenges dieting wisdom that is taught to doctors, nutritionists, dietitians, PhDs and personal trainers, particularly the "eat less, move more" mantra.

His findings suggest that, consistent eating at higher calorie levels can lead to metabolic improvements and fat loss, contrary to the expectation that high calorie intake always leads to weight gain.

This is an unexpected detail, as most people associate high calories with weight gain, not loss.

Although if you are dogmatic enough to believe that metabolisms don’t down regulate, I can imagine thinking that they can up-regulate would cook your brain.

I did find some controversy around the applicability and safety of such high calorie diets.

Another chat on the former Ray Peat forum, highlighted that while Billy is seen as knowledgeable and credible, his experiment is considered extreme.

Some argued it is not suitable for beginners or the general population, with concerns about the health risks of such high metabolic rates and the reliance on candy.

I found all this research hilarious.

So many peaters complain of weight gain in trying up up-regulate their metabolisms and I think no one considers their own context when attempting this.

If you start at 3500kcal TDEE, moving to 3750kcal is a 7% increase.

But if you’re coming from 2000kcal TDEE and moving to just 2250kcal you are making a 12% jump! You also are starting from a much less productive place which would suggest your increases need to be a smaller % than when the train is already going.

Billy's work also touches on the psychological aspects of dieting, as seen in his book, which discusses how restrictive diets can lead to feelings of failure and compensatory behaviors.

Recap

Experiment Period

2004-2006

Calorie Levels Tested

3500 calories, 4500 calories, 6000 calories

Final Calorie Intake

6000 kcal per day at 10st (weight)

Exercise Levels

Remained roughly the same (teaching spin classes, competing as usual)

Observations

Body temperature increased, no fatigue, fat levels fell dramatically, metabolism rose to match intake, suspected hyperactive thyroid, struggled without food for longer than an hour

Health Risks Noted

Being at either end of the metabolic spectrum comes with health risks, ideal range for the individual was 3200-3600 kcal

Food Source

By the end of the experiment he required junk food (candy) for ease of counting and carrying

Consistent Eating (Billy’s Book)

I picked up Billy’s book in an attempt to fill in some of the gaps in my understanding of this story and with hope that he, maybe, had broken down what he did into a protocol someone else could follow.

He does not lay out a protocol. Instead his book, which again was published 12 years after his original experiment ended, makes a detailed, scientific and enthralling case that:

• Repeated calorie restriction can put a human in a state of Torpor (metabolic hibernation) which previously I had only thought could happen from eating Omega-6 fats.

• A suppressed or efficient metabolism is correlated with early aging, and people who live well past the median lifespan have high metabolisms

• One of the ways your body becomes “more efficient” is to shrink your kidneys, digestive tract and other organs whilst sparing your brain and heart (your liver actually gets bigger as the need for gluconeogenesis in starvation is greater)

• High protein diets increase calorie restriction without realizing it and may be suppressing your metabolism

• 3 meals a day plus snacks is a result of social conditioning and not conducive to an optimal metabolism.

The book refers to a second book that will come, although, with 6 years since publishing, there is no sign of a second book.

How does it fit in?

Well to be quite honest with you. Billy’s story and his book were a breath of fresh air (besides the fact that the entire book is in italics which is rather annoying).

Everywhere we look, read, hear is the message eat less, do it harder.

Just this year famed bodybuilding coach Lyle McDonald who popularized protein sparing modified fasts recommended taking thyroid hormones and GLP-1s when approaching his extreme dieting approach to the dismay of many followers who have attempted his “Rapid Fatloss” protocols and failed.

What he managed to do, and the case he put forward is one that many in this space have discussed. It feels right, but modern science has basically ignored it.

I find it partially terrifying to think people are regularly shrinking their organs through fasting and restriction. Repairing that metabolic damage will likely take years.

A high metabolism makes sense as the ultimate longevity hack too. At a higher metabolism you can detox faster, hypervitaminosis is less probable. You have more energy to spare for heat and immunity and repair and brain function.

Eating consistently to force your feedback systems to learn that you are in an energy abundance makes sense too. I keep imagining a flywheel in my head. You want to keep it running. Just give it a little push over and over.

People with low metabolisms and low thyroid complain of constipation. Maybe having a slowed metabolism and then eating 33-50% of your entire food load in one go is a recipe for disaster? It takes energy to digest a huge bolus of food. I would bet smaller consistent mini meals would rapidly speed up digestion.

In fact, I actually think this might be what is critically missing in the pro-metabolic diet space. The honey diet seems a LOT more reasonable if you are microdosing honey in the feeding window rather than trying to replace your normal meal volumes with honey.

Conclusion

The last three weeks posts took a lot of 6am and 8pm reading and writing time, but have seemingly, like always in my life, come at the perfect time.

I now fully understand what I have done to myself, where my metabolism and thyroid is at and where I want to be. I hope you do to.

Based on Billy’s work I have made some changes in my life to be reported on soon and we’re incorporating broad stroke metabolic screeners and opinions in our work at Patchwork.

I hope this post leaves you enlightened and empowered. Happy Saturday everybody.

p.s. If you came here via substack, you might like more more frequent postings on X.

p.p.s Thanks for answering the poll last week! We made some awesome changes at patchwork and are soon incorporating OATs to see how your energy generation system is broken (see below)

In this week's post, I want to look at something fun, which is your metabolism and how it stacks up against the leading loudest health influencers online.

We look at Abbey Sharp, Andrew Huberman, Becca Bristow, Brian Johnson, Cole Robinson, Durian Rider, Gabrielle Lyon, Jay Feldman, Kate Deering, Marc Lobliner, Mark Hyman, Mark Sisson, Meghan Livingstone, Mike Israetel, Mike Matthews, Mindy Pelz, Nick Bare, Paul Saladino, Robb Wolf and Shawn Baker.

In a perfect world, the idea that you can exercise more and eat more and it will raise your metabolism is a reasonable one if you have perfect metabolic flexibility and no history of thyroid or metabolic suppression.

On the flip side, the idea that you can eat less and move more and that will lead to weight loss makes sense if you have good metabolic flexibility and no history of suppression either.

I think understanding that, explains why when you are extremely young and you haven't done too much damage to your body/ you haven't accumulated too much PUFA in your tissues you can simply crash diet lose the weight real quick.

But most of the people that I deal with and talk to are at a place where everything they tried in the past doesn't work, and now they're completely stuck.

This post explores two things:

1. The incredible work done in mapping people's metabolisms to their lean body mass using doubly labeled water which allows you to see where you line up on how suppressed your metabolism might be

2. Looking at the publicly available body stats and diets of loud online health influencers and mapping back what their energy availability and metabolism looks like

Where does your metabolism sit?

In the paper "Daily energy expenditure through the human life course" published in Science 13 Aug 2021, Vol 373, Issue 6556, pp. 808-812 DOI: 10.1126/science.abe5017

Researchers investigated the effects of age, body composition, and sex on total expenditure using 6500 people across 29 countries who were 64% female using doubly labelled water (gold standard metabolism measurement).

They found that "both total and basal expenditure increased with fat-free mass in a power-law manner" which is on the whole unsurprising. However, this power-law was incredibly tight and as such can be used to reasonably expect with a high degree of confidence where you metabolism both should be and could be.

The results and power-law trend line are seen below

Run your numbers

To put yourself on this graph you need a few things. has done great work in making the chart interactive here, where you can plug in your numbers when you have them.

Numbers needed:

• Total Weight

• BF% estimate

• Your weight stable total calorie intake (how much you can regularly eat and not gain weight)

• Work out your Fat Free Mass = Total Weight * (1 - bf%)

So for me - I’m now 165lbs, and can regularly eat 2500kcal and remain 18% bf

So my FFM = 165 * (1-0.17) = 135

Which puts me here on the charts with about a 15-20% suppressed metabolism.

My TDEE was just shy of 2000kcal in September so… progress!

So what about your favorite influencer?

One of the reasons why this is important is, we follow these people. We mimic them. We think if they can do it, we can too. But in doing so miss pretty key context… are our metabolisms the same?

Before we dive in - have you done the poll in the first section of this post where I asked for a favor? It would mean a WHOLE LOT to me if you could help out - it’s a simple poll.

Based on publicly available “What I eat in a day” videos, and claims about body stats I have been able to reverse engineer what the energy intake, weight, BF%, Lean body mass or Fat Free Mass and Calorie per lb of LBM is for:

(Women in bold)

• Abbey Sharp

  • Daily Diet: Yogurt (200 g), granola (50 g), berries (100-150 g), eggs (2-3 occasionally), chicken/salmon (12-16 oz), carbs (300-400 g quinoa, rice, pasta, sweet potato), fats (90-110 g olive oil, PB, avocado), veggies (450-600 g), snacks (apple, hummus, crackers, cheese), occasional chocolate.

  • Macronutrients: ~100-120 g protein (17-20%), ~90-110 g fat (34-41%), ~310-370 g carbs (52-62%)

• Andrew Huberman

  • Daily Diet: Steak or beef (~500 g), whey protein (40 g), Brazil nuts (30 g), olive oil (30 g), vegetables (300 g), oatmeal (75 g), sweet potato (150 g), adjusted for training.

  • Macronutrients: ~170 g protein (29%), ~147 g fat (55%), ~106 g carbs (18%) on training days.

• Becca Bristow

  • Daily Diet: Oats (75-100 g), yogurt (100-150 g), chicken/salmon (12-16 oz), carbs (300-400 g rice, quinoa, sweet potato), fats (90-110 g PB, AB, olive oil, butter, cream), veggies (400-600 g), berries (~100-150 g), snacks (banana, cottage cheese, crackers), occasional chocolate/wine.

  • Macronutrients: ~100-120 g protein (17-20%), ~90-110 g fat (34-41%), ~310-370 g carbs (52-62%)

• Brian Johnson

  • Daily Diet: Matcha smoothie, nutty pudding, variable main (e.g., chickpea curry), Blueprint stack, all by 11:30 AM.

  • Macronutrients: ~50-60 g protein (19%), ~120 g fat (48%), ~155 g carbs (33%).

• Cole Robinson

  • Daily Diet: Fasts 16-48+ hours with Snake Juice, refeeds with ~3-4 kg fruit (watermelon, bananas), 2-3 L juice, ~150 g sugar, ~250 g lean meat every 3-5 days.

  • Macronutrients: ~47 g protein (5%), ~15 g fat (4%), ~915 g carbs (91%)

• Durian Rider

  • Daily Diet: 40 bananas (4 kg), rice (700 g cooked), dates (300 g), watermelon (1 kg), greens (200 g).

  • Macronutrients: ~76 g protein (5%), ~18 g fat (3%), ~1,373 g carbs (92%)

• Gabrielle Lyon

  • Daily Diet: Eggs (5), beef/chicken/steak (20-26 oz), whey (30-40 g), carbs (150-200 g sweet potato, rice, berries), fats (90-110 g avocado, oil, ghee), veggies (300-500 g), broth (~250 mL).

  • Macronutrients: ~150-170 g protein (21-24%), ~90-110 g fat (29-35%), ~150-200 g carbs (38-43%)

• Jay Feldman

  • Daily Diet: OJ (500 mL), coffee with cream/honey, eggs (2-3), gelatin (10 g), beef/lamb (12-16 oz), rice/sweet potato (400-550 g), fruit (700-900 g), milk (500 mL), cheese (50-100 g), dates/honey (150-200 g), coconut oil (14 g), ice cream (~200 g).

  • Macronutrients: ~100-120 g protein (13-15%), ~100-120 g fat (28-34%), ~400-450 g carbs (50-56%)

• Kate Deering

  • Daily Diet: OJ (500 mL), coffee with cream/sugar, eggs (2-3), gelatin (10 g), beef/shellfish (12-16 oz), rice/sweet potato (350-400 g), fruit (700-900 g), cheese (50-100 g), milk (500 mL), dates/honey (150-200 g), coconut oil (15 g), ice cream (~200 g).

  • Macronutrients: ~90-110 g protein (15-18%), ~90-110 g fat (25-30%), ~350-400 g carbs (52-57%)

• Marc Lobliner

  • Daily Diet: 2-2.5 lbs meat (steak, beef, chicken, bison), whey (30-40 g), carbs (300-400g rice, sweet potato, buns), fats (100-120 g olive oil, PB, eggs), veggies (~400-600 g).

  • Macronutrients: ~250-275 g protein (31-34%), ~100-120 g fat (28-34%), ~310-370 g carbs (34-39%)

• Mark Hyman

  • Daily Diet: Coffee with MCT, eggs (2-3), salmon/lamb/chicken/bison (12-16 oz), veggies (500-600 g), fats (120-140 g from ghee, oil, avocado, nuts), berries (~100-150 g), occasional chocolate.

  • Macronutrients: ~100-120 g protein (20-24%), ~120-140 g fat (54-63%), ~50-70 g carbs (10-14%)

• Mark Sisson

  • Daily Diet: Coffee with cream/sugar, eggs (2-4), fruit (100-200 g), salad with chicken/fish (6-8 oz), steak (10-12 oz), veggies (400-500 g), fats (130-150 g from avocado, nuts, dressing), occasional wine/chocolate.

  • Macronutrients: ~120-140 g protein (21-24%), ~130-150 g fat (56-59%), ~90-110 g carbs (16-19%)

• Meghan Livingstone

  • Daily Diet: Oats (75-100 g), lentils/chickpeas/salmon (4-8 oz), carbs (300-400 g quinoa, rice, sweet potato), fats (80-100 g almond butter, tahini, olive oil, avocado, walnuts), veggies (400-600 g), berries (100-150 g), snacks (banana, muffin).

  • Macronutrients: ~70-90 g protein (13-16%), ~80-100 g fat (33-41%), ~310-370 g carbs (56-67%)

• Mike Israetel

  • Daily Diet: 2-2.5 lbs meat (chicken, turkey, steak, salmon), whey (80 g), carbs (400-500 g oats, rice, sweet potato, quinoa), fats (90-110 g olive oil, avocado), veggies (~500-800 g).

  • Macronutrients: ~250-275 g protein (26-29%), ~90-110 g fat (21-26%), ~410-470 g carbs (43-49%)

• Mike Matthews

  • Daily Diet: Whey (70-80 g), chicken/beef/steak (24-30 oz), carbs (300-400 g oats, rice, sweet potato), fats (80-100 g olive oil, PB), veggies (300-600 g), yogurt (200 g), occasional chocolate.

  • Macronutrients: ~200-220 g protein (27-29%), ~80-100 g fat (24-30%), ~310-370 g carbs (41-50%)

• Mindy Pelz

  • Daily Diet: Fasts 12-17 hours, then ~12-16 oz meat (beef, salmon, chicken), eggs (2-3), fats (130-150 g avocado, olive oil, ghee, cheese), low-carb veggies (400-600 g), berries (100 g), broth (250 mL).

  • Macronutrients: ~90-110 g protein (20-22%), ~130-150 g fat (65-70%), ~20-30 g carbs (5-6%)

• Nick Bare

  • Daily Diet: ~2 lbs meat (beef, chicken, steak, bison), whey protein (60 g), oats (100 g), rice/pasta (350 g), sweet potato (200 g), fats (peanut butter, avocado, olive oil), veggies (300 g).

  • Macronutrients: ~260 g protein (33%), ~120 g fat (27%), ~375 g carbs (40%)

• Paul Saladino

  • Daily Diet: ~1.5 lbs grass-fed red meat, 0.5 oz liver, 1 L raw milk, 700 g fruit, 100 g honey, small amounts of raw sour cream and butter.

  • Macronutrients: ~192 g protein (23%), ~183 g fat (50%), ~222 g carbs (27%).

• Robb Wolf Daily

  • Diet: Eggs (3-4), bacon (60-120 g), beef/pork/salmon/chicken (16-20 oz), rice/sweet potato (350-500 g), veggies (400-500 g), fats (100-120 g from MCT, ghee, oil, nuts), berries (~100 g), occasional chocolate.

  • Macronutrients: ~180-200 g protein (24-27%), ~100-120 g fat (30-36%), ~210-270 g carbs (28-36%)

• Shawn Baker

  • Daily Diet: 3-4 lbs ribeye steak (1.36-1.81 kg), occasional eggs or bacon, water only.

  • Macronutrients: ~350 g protein (35%), ~300 g fat (65%), 0 g carbs (0%).

So let’s see how they stack up

When ranked by Calorie per lb of Lean Body Mass I was shocked to see the likes of Mark Hyman, Mark Sisson and Andrew Huberman at the bottom of the list.

Mindy Pelz’s entire case is for aggressive and repeated fasting so a suppressed metabolism didn’t surprise me at all.

Brian Johnson also actively tries to lower his body temperature (a great marker of metabolism) whilst still taking thyroid medication to artificially manage it so no surprise there either.

Durian rider eats mostly sugar and rides a bike all day - no surprise there.

I will say Nick Bare surprised me. Body builder types who have a history of dieting down to get lean typically present with a suppressed metabolism.

Kate Deering being in the top five made me feel warm inside given her history of aggressive dieting and the way it destroyed her body as detailed in her book How to Heal Your Metabolism.

So where do they sit on the chart?

In the interest of simplicity I labelled the chart with numbers rather than their names.

Once on the graph I’m actually concerned how many people try to mimic the lives of some of these people. So yeah, choose your favorite health influencer wisely.

Hey could you do me a favor and make sure you answer the poll near the top of this article.

At Patchwork, when we do a nutrigenomic screening, we'll always welcome any additional context or tests that users have and want to share with us.

One that is of particular interest to us and the discussion of which comes up every time we do a consult is someone's thyroid numbers.

Time and time again, users come to us and say they feel cold, they feel sluggish, they can't pull energy from their food, but their doctor is convinced that there's nothing wrong with their thyroid.

And having read more countless books and several hundred papers on thyroid, I wanted to share some of the science that I know and that has formed my view on how the thyroid works and how to really diagnose if something is going on there.

The problem with TSH

You might know that TSH (Thyroid-Stimulating Hormone) is the hormone that we use to measure hypothyroidism.

But what you probably don't know is that TSH isn't actually made by your thyroid. It's made by your pituitary gland.

And this is where things can get a bit tricky.

If your pituitary gland isn't functioning optimally, it might not be producing enough TSH, leading to a false negative on a traditional TSH test.

Furthermore for your pituitary gland to release TSH, it needs feedback from the body that it needs more thyroid hormone. This feedback is mediated through the hypothalamus, which releases thyrotropin-releasing hormone (TRH) to stimulate the pituitary gland. If there's any dysfunction in this feedback loop, it can result in an inaccurate TSH reading.

So relying solely on TSH levels may not provide a comprehensive picture of thyroid health.

And if your curious - before TSH, the medical establishment used to be obsessed with a test for something called PBI (Protein-Bound Iodine) as a measurement for hypothyroidism, which was proven totally unreliable after 30 years of use!

To get a more accurate assessment, it's important to consider other thyroid hormones like free T4 and free T3, as well as clinical symptoms and patient history.

But what if your cells are resistant to T3 uptake?

What if your liver is damaged or running slow (from say...a lack of choline) and T4 is not converting to T3?

What if you have a history of aggressive dieting and your body suppresses T4 to T3 production?

I wanted to share some studies that further the issues with TSH and aggressive dieting on the whole.

What excessive dieting does to your Thyroid

It seems like every day I see an argument erupt on weight loss reddit over whether "starvation mode" exists.

It's borderline comedy at the point because we know this:

• less than 3% of Americans who successfully lose weight keep it off

• when properly tracked aggressive diets lead to rapid reductions in TDEE

• dieting the first couple times seems to work but always seems to stop working

Could it be due to some of the science below?

Effect of long-term calorie restriction with adequate protein and micronutrients on thyroid hormones

The Journal of Clinical Endocrinology & Metabolism, Volume 91, Issue 8, 1 August 2006, Pages 3232–3235, https://doi.org/10.1210/jc.2006-0328

In this study published in 2006 scientists found that long-term calorie restriction, even with adequate protein and micronutrients, resulted in decreased levels of T3 and T4 hormones. This suggests that aggressive dieting can directly impact thyroid function, leading to a slower metabolism and potentially hindering weight loss efforts.

When calories returned to maintenance - T3 levels remained 20% suppressed. By all accounts, the study showed that participants sliced off 20% off their metabolism somewhat permanently.

The effect of caloric restriction and glycemic load on measures of oxidative stress and antioxidants in humans: results from the CALERIE trial of human caloric restriction

Caloric Restriction and Glycemic Load on Measures of Oxidative Stress and Antioxidants, Published: 11 January 2011, Volume 15, pages 456–460, (2011)

Another study titled "The effect of caloric restriction and glycemic load on measures of oxidative stress and antioxidants in humans: results from the CALERIE trial of human caloric restriction" published in 2012 found that caloric restriction led to a decrease in T3 levels, further supporting the notion that extreme dieting can negatively affect thyroid function.

Again in this study - when calories returned to maintenance - T3 levels remained 20% suppressed. Participants sliced off 20% off their metabolism somewhat permanently.

Thyroid Hormone Transport into Cellular Tissue

Journal of Restorative Medicine, Volume 3, Number 1, 4 January 2014, pp. 53-68(16)

Another study, titled "Thyroid Hormone Transport into Cellular Tissue" published in 2014, delved into the mechanisms behind thyroid hormone transport and its implications for overall thyroid function. This study shed light on how disruptions in this process, such as those caused by extreme dieting, caloric restriction and aging, can lead to long-lasting changes in metabolism and hinder weight loss efforts.

The study found that caloric restriction not only affects T3 levels but also disrupts the transport of thyroid hormones into cellular tissue, which can have long-lasting effects on metabolism. This suggests that extreme dieting can lead to metabolic adaptations that make it difficult to lose weight and maintain weight loss in the long term.

Furthermore, the study highlighted the limitations of using TSH as a sole diagnostic tool for hypothyroidism in individuals with a history of stress or aggressive dieting. It emphasized the importance of considering other factors, such as symptoms and comprehensive thyroid hormone testing, to accurately diagnose and manage thyroid disorders in these populations.

In the image above - it doesn't take much for TSH & T4 levels to be an inaccurate indicator of thyroid function and metabolism.

Or put another way - the more stress you put your body under, the lower the utilization of T3 hormones and thus most thyroid markers are rendered useless.

Bear in mind that in a modern environment our bodies are under attack from an endless stream of environmental stress, where each stressor may be minor but incremental in increasing the overall load.

This is further displayed in the image below

The surprising finding in this study, to me at least, was the authors clear guidance on how to diagnose hypothyroidism given this context - and is how we now think about it at Patchwork.

"Additionally, the most rigorously screened individuals for absence of thyroid disease have a TSH below 2 to 2.5 mU/L. Thus, treatment should be considered in any symptomatic person with a TSH greater than 2 mU/L. As discussed, a free T3/rT3 ratio below 0.2 is a useful indicator of low tissue thyroid levels. Additionally, a relatively low SHBG, a slow reflex relaxation time, a low resting metabolic rate (metabolism), and a low basal body temperature can also be useful indicators of low tissue thyroid levels and can aid in the diagnosis of tissue hypothyroidism."

Ways to diagnose:

• Symptomatic and TSH above 2

• T3/rT3 ratio below 0.2

• Relatively low SHBG

• Slow reflex relaxation time (ankle test)

• Low resting metabolic rate

• Low basal body temperature

For context - my thyroid numbers have been all over the place but since mega dosing raw desiccated thyroid my numbers finally looked healthy this year.

I do however have a low metabolic rate, low basal body temperature and a T3/rT3 ratio of 0.2 exactly WITH natural supplementation. Something I continue to work on.

Conclusion

You don’t have to be a conspiracy theorist to read up on thyroid and see why doctors so often get it completely wrong. If there is one part of your health to which you should fully take control, it is your thyroid. It drives everything.

Next time you do bloods, or your physical is due. Demand that free T3 and reverse T3 get tested too.

The maths on the ratio is simple, but just to be sure - Patchwork is building an easy calculator to check.

This week I had the honor of presenting what Patchwork is working on a the Boulder New Tech meetup in front of 200 people.

Talking about metabolic health with a single person let alone 200, can make people really uncomfortable (understandable) so I decided to mix it up and simply run the audience through some studies which were fundamental in opening my mind to the idea that weight gain is way more complex than calories in calories out.

On every slide there were audible gasps from the audience.

I think partly because everyone has biases in this space that they had to address, and partly because no one wants to think about this - if you are struggling with weight issues it can consume 90% of your mental energy on any given day.

My goal for the later, was to offer understanding and a glimmer of hope that there are people that understand this and working really really hard to crack it (us!)

So I thought it would be fun to share four of these studies with you all.

Just last week I encountered more closed thinking.

Weight Gain After Fecal Microbiota Transplantation

In this study a weight stable, healthy weight mother recieved a fecal transplant from her overweight daughter as part of CDiff treatment.

Within 16 months the mother gained 34 pounds hitting a BMI of 33.

In response to this she was put on a medically supervised, liquid protein diet, wherein she continued to gain weight despite efforts to diet and exercise, and at 36 months post-FMT her weight was 177 pounds (BMI of 34.5). She also developed constipation and unexplained dyspeptic symptoms.

After this case the policy was changed to use nonobese donors for FMT going forward.

Sustained bloodstream release of persistent organic pollutants induced by extensive weight loss after bariatric surgery: Implications for women of childbearing age

• 100 morbidly obese patients were screened before and 3, 6 and 12 months after bariatric surgery for serum concentrations of PCBs, OCPs, BFRs, and PFASs.

• Patients underwent bariatric surgery

• Patients had weight loss averaging 30% of initial body weight at 12 months

• One year after surgery, serum pollutant levels increased up to 130%.

• When Lipophilic persistent organic pollutants are elevated (above tolerance) in your blood, your body forces you (hormonally) to seek out obesognic foods (junk food) to gain weight and store them away in adipose tissues. These are released in weight loss. And a good case for why people regain weight lost.

Effect of long-term calorie restriction with adequate protein and micronutrients on thyroid hormones

• 28 adults

• 6 years of calorie restriction @ 1700kcal

• Compared to a western diet group (2500kcal) & a high exercise group (2800kcal)

• Long-term Calorie Restriction with adequate protein and micronutrient intake in lean and weight-stable healthy humans led to a permanent reduction in serum T3 (20% lower!)

• The reduced calorie intake permanently wiped off 20% of their calories out!

Dietary protein restriction elevates FGF21 levels and energy requirements to maintain body weight in lean men

• 8 lean healthy men

• Followed a Low Protein High Carb diet for 5 weeks (~0.5g/lb bodyweight)

• To prevent weight loss, it was necessary to increase energy intake consecutively every week

• By the end of week 5 participants were eating 20% more calories than in week 1 and still accidentally lost 2lbs over the 5 weeks

• The cohort was then put on a high protein diet for 5 weeks and had to reduce food intake to try and prevent weight gain. (~1g/lb bodyweight)

• Physical activity was held the same across the entire study

Conclusion

These issues are wildly more complex than 99% of people understand (not you, because you read uncivilized).

But I like to pull out these studies from time to time just to get some idiot with dumbass biases to shut up.

A quick excerpt from a coaching call:

Me: “So, all of this means that you probably have been pathologically not detoxing aldehydes properly your entire life. I'm surprised that you haven't had any kidney stones by this point, to be honest.”

Them: “Wait, say that again”

Me: “The primary cause of kidney stones is a stuff called oxalate. What people don't realize is that 90% of oxalates are actually produced inside of the human body. Fundamentally, they are produced via something called the glyoxal pathway, which comes from eating linoleic acid (seed oils). And from your genetics we can see that you will have had a seriously slowed detox of seed oils your whole life if you ate them.”

Them: “I’ve had 7 kidney stones, nephrologists could never understand why”

Me: “Yeah it’s the seed oils”

I remember this like it was yesterday - what seemed like an innocuous fact lit up our client face as she could unpick another mystery that medicine couldn’t help with in her body. I explain how it all works below, but here’s some reviews on Patchwork’s work so far.

How does this all work

• Kidney stones are caused by circulating oxalates in the body

• Over 90% of oxalate is produced internally, with linoleic acid oxidation via lipid peroxidation playing a major role by generating glyoxal, a precursor to oxalate, which contributes to kidney stone formation.

• Oxidized LDL, derived from oxidized linoleic acid, leads to podocyte apoptosis and foam cell formation in the kidneys, resulting in glomerulosclerosis (scarring) and impaired renal function.

• When taking into account the full body of literature and human biology, it is clear that dietary linoleic acid is the primary driver of kidney stones in humans

Involvement of Linoleic Acid in kidney stones​

Emerging evidence suggests that the majority of oxalate in the body is produced endogenously, with over 90% of urinary oxalate being synthesized internally rather than obtained from dietary sources.

This insight shifts the focus of kidney stone prevention from external dietary oxalate intake to the internal metabolic processes that contribute to oxalate production, particularly in individuals without major gastrointestinal surgery that would otherwise increase dietary oxalate absorption.

Oxidized Polyunsaturated Fatty Acids (PUFAs) and Oxalate Production
Linoleic acid, a commonly consumed polyunsaturated fatty acid (PUFA), undergoes non-enzymatic lipid peroxidation, leading to the formation of various oxidation products, including glyoxal. Glyoxal is hypothesized to be a significant precursor of endogenous oxalate synthesis in humans.

The conversion of glyoxal into oxalate represents a key metabolic pathway, linking lipid peroxidation of PUFAs like linoleic acid to kidney stone formation.

Several detoxifying enzymes, such as aldehyde dehydrogenase (ALDH), play a role in managing glyoxal levels, but when oxidative stress is high and the balance of reactive oxygen species is disturbed, the body’s ability to detoxify glyoxal may be overwhelmed.

This can lead to an accumulation of oxalate, a critical factor in the formation of kidney stones.

Oxidized LDL and Renal Injury
Beyond oxalate production, oxidized low-density lipoprotein (oxLDL) plays a direct role in kidney damage. OxLDL is a modified form of LDL that arises when lipoproteins containing PUFAs like linoleic acid become oxidized.

Studies have shown that oxLDL, but not native LDL, induces apoptosis (programmed cell death) in kidney cells known as podocytes. These cells play an essential role in maintaining the filtration barrier in the kidneys.

Their damage leads to glomerulosclerosis, which is essentially the arteriosclerosis of the kidneys—a condition marked by scarring and stiffening of the glomerular structures.

Human glomerular mesangial cells (HMCs), which provide structural support in the kidney’s glomerulus, also take up oxLDL under inflammatory conditions.

In the presence of inflammatory cytokines like Interleukin-1β (IL-1β), these HMCs ingest oxLDL beyond their scavenging capacity, becoming foam cells.

Foam cell formation in HMCs contributes to glomerulosclerosis and renal injury, further impairing kidney function and potentially exacerbating oxalate accumulation due to reduced renal filtration efficiency.

The connection between linoleic acid oxidation, endogenous oxalate production, and renal damage is a critical but often overlooked factor in kidney stone formation and progression of renal disease.

While dietary management of oxalate intake has traditionally been emphasized, reducing the intake of linoleic acid, and controlling oxidative stress within the body is equally if not more important in mitigating the risk of kidney stones and protecting overall kidney health.

But I’m carnivore, this doesn’t apply to me

Unfortunately, it absolutely does.

Chicken, Duck, Turkey and Pork fat is essentially a seed oil.

Those pork rind covered chicken thighs you eat regularly will be full of Linoleic Acid.

In fact, that salad you are afraid of is less harmful than the pork rinds you eat.

Stick to beef & other ruminants if you want to save you kidneys.

This week's topic comes to you to the benefit of my X followers who, when asked which of two topics should I write about, overwhelmingly said they want to know more about food noise.

Background

One of the major disconnects that drove me to start Patchwork was that people who have been relatively lean their entire life and managed to move give or take 15 pounds of body fat up and down seem to think that their experience and their advice can be applied to somebody who is significantly overweight or even obese.

Having just written that down, you must realize how absolutely absurd such an idea even is.

Yet it continues - almost every diet or food influencer on the internet has never really understood what it is like to struggle at the higher end of the scale and then to successfully come down.

And the one major disconnect that I'm going to dig into today, which these influencers cannot even begin to empathize with, is the issue of food noise.

Here's my caveat. I believe that in the last year I have suffered from acute food noise at times which led me to seek out other people who have suffered from food noise. I've now spoken to over a thousand people who have dealt with this issue.

Furthermore, the only existing modern solution is basically taking a GLP-1ra’s, and Patchwork is building the solution to this that doesn't need drugs. We’ve understood the drivers and causes, what you need to do to calm it and ultimately solve it.

The goal of this post is to hopefully give you a basis to build some empathy with your fellow humans and understand just absolutely how hard it is to suffer with this issue.

And I have to state - No, therapy will not solve this issue. Not sure where this idea came from but it is unhelpful to the sufferers.

So what is food noise and what does it feel like?

One of the insane things about food noise is that doctors have only really started to put a name to it in the last two to three years and they have absolutely no understanding of it.

Any attempt by me to explain what it actually is would do a disservice to those suffering from it.

So, what I'm going to do below this is just give you excerpts of quotes from all of the conversations I've had in the past year - so you can hear directly from the sufferers. Each quote is from a different person/conversation.

You need to separate this from hunger. Many sufferers call it hunger because we don’t have good language for it yet. This is not a grumble in your stomach or getting hangry. This is not craving a specific food from nutrient deficiencies.

This is a hormonally driven subconscious directive to gain weight. Any person that things “discipline” or “fasting” or “calorie counting” can beat this is a oaf.

I feel like I am doomed to either become obese or to spend the rest of my life fighting this. It is miserable. I want to sustain a healthy lifestyle so bad but I am in absolute disbelief at how wild my brain is trying to force me to eat all the time, for no reason.

I was shocked to discover there’s a name for something I’ve been struggling with for so long. You just have a constant, intrusive stream of thoughts about food—what to eat, when to eat, and how much to eat.

the most distressing for me was the rapid weight gain and insatiable hunger. I’m a little over 5’10 and I went from a very comfortable 140lbs to probably 180lbs in 18 months. For much of that time I was absolutely RAVENOUS for no apparent reason, and it was so upsetting because I didn’t know what to do and I couldn’t seem to stop the weight gain!…

…I could easily eat 2000 calories before noon and still be hungry…

…It was hellish and so confusing

The constant thinking of food. For instance, when I’m eating breakfast, I am planning my other meals. Food noise is the nagging voice in your head telling you to eat all the cookies you had your husband hide from you. Food noise is searching my house endlessly to find something that tastes sugary.

I obsess over food. I spend my whole day thinking about it, what I ate last, what I want to eat next, what I could eat this weekend. I think about cookies and cheese and fried chicken and the damn desire to eat takes up so much of my mental energy.

If i touched fast food it would go very bad for me because something about my body makes me easily addicted to food. I actually dont really like sweets, my body never really longs for cake

The inability to stop. I could be full and have the container of ice cream in front of me after having ate a good amount and food noise is “one more bite one more bite”

Also thinking of food constantly. My mood depended on food. Being at for example the bakery getting a muffin and a coffee and also saying “wow that scone looks good. I NEED that scone AND the muffin.”

When you have issues with food, it’s just all foods. There’s not much distinction. For some they have never experienced not having that.

I cannot get rid of the constant raging voice that tells me to eat just for the sake of eating. It yells to EAT THIS; EAT THIS; EAT THIS NEXT; WHAT ARE WE EATING NEXT, completely regardless of what is going on. I could be literally finishing a huge meal, the voice will yell to eat some next thing, even though I actively do not want to eat any more food, I know for a fact I am not hungry and I do not need any more.

Want to Everything. All the time.

For me it was any junk food that was located near a destination I was already going go - like a Krispy Kreme near Costco. Since I was going to Costco, I felt like I deserved a donut - or three.

All of it. People who hear food noise, hear it 24/7 about any kind of food.

I craved nachos more than any other food. My sinuses were partly blocked and it diminished my sense of smell and taste. The texture was just as important as the taste and spiciness

For me, it's better described as hunger noise. Eat a normal meal and be starving 30 minutes later and thinking about what is the next meal, and when can I eat it. And white knuckling until I could.

However, when I would finally say f-it, I can't take this anymore, and eat I would certainly reach for tasty foods. And we have an inate drive to eat the most calorie dense foods available, so it's hardly surprising. So, would I eat cheese and crackers v carrots, of course. But that doesn't meal that food noise was only from cheese and crackers.

Obsessing about all food, planning the next meal as soon as I finished one. It became the first priority to make sure I carry snacks, as if I might starve.

I was never driven for like normal homemade meals. Like my food noise wasn’t “omg I need some baked chicken” more like “omg I need a pizza”

A few minutes after I wake up, I start planning breakfast in my head, even though I won’t eat for 2–3 hours because I first walk my dogs, work out, and take care of a few other things. Within 30 minutes of eating breakfast, I find myself thinking, “Three more hours till lunch.” The cycle continues throughout the day. Lunch, dinner—it’s all the same. It feels like a significant part of my mental energy is always focused on food.

After dinner, it’s an even bigger challenge. I constantly battle the urge to snack, and I don’t always win that struggle.

I held out. I said "I have to figure this out!" But I'm 42 now and I'm not getting any younger and I've been trying to figure it out for 15 years. I'm tired. And now I realize I was battling hormones, something outside of my control. I was never going to figure it out. So I just ate, but the noise doesn’t go away, you just get bigger and bigger.

I quit drinking by making ONE decision. I quit smoking by making ONE decision. I have to decide about eating over and over and over again, every day.

I was thinking today that it's like I have two brains that don't communicate with each other. One says, "I don't want to be overweight anymore. I won't overeat today. I'll make better food choices. I can not tolerate continuing to not lose weight."

The other says, "Hm maybe I should have a milkshake."

It's so frustrating.

It took over my life for years. For me, I’ve come to terms with the fact that I’ll never totally eliminate it, but I have managed to turn down the volume considerably.

I am always hungry. I've even done a 3 day water only fast, so I know what actual hunger is. But, I don't really feel satisfied when I am done with a meal. I could eat a huge dinner and still crave junk.

When it's strong, I usually find myself watching loads of cooking content and reading recipes and planning meals

Omg there’s a term for this!?

I’ve had food noise for 20 years!!!

I struggle with this tremendously. It’s constant. Ive gained so much weight due to food noise. I don’t know what to do. I feel so defeated.

Food noise is a side effect of me being at my preferred weight. I had to accept that it doesn’t go away. I live with it and what really helps is having lots of low cal raw veggies or pickled things as snacks

I think about food and meals constantly even if I've just eaten.

I've struggled with this my entire life.

I just started hearing food noise when I started dieting.

I have lived with food noise for so long it wasn’t until I heard the term last year that it dawned on me that I had it.

My "food noise" only happens at night, around 9 PM, it's this constant biatch in my ear, saying, EAT, and I say, stfu I'm not hungry. But there I am, in the kitchen, in the cupboards finding anything to eat.

It drives me nuts. It is absolutely insane and I can genuinely say that it is unbearable to a point where my quality of life is severely impacted.

Unfathomable urges to eat on a binge-level, as strong as urges to pee. Constant, obsessive thoughts about food. The thoughts are intrusive and raging inside me like no tomorrow.

It doesn't matter that I physically resist and not cave in, such as not buying things, not visiting certain places - I am spending a CRAZY amount of willpower on it, throughout the entire day, and that is just exhausting. It doesn't matter that I win this battle. Just the fact that I have to fight these absurd mental struggles ALL THE TIME drains so much energy and joy out of me.

I feel like I lack mental capacity and concentration in many other things because I am spending so many "brain resources" on battling not to snack and overeat ALL THE TIME. A reaslistic estimate is that in 1 hour, I spend 40 minutes thinking about food. I feel uncomfortable around trigger foods, in supermarkets, at events I experience serious distress and by that I don't mean uneasy, I mean literal anxiety-attack niveau, full blown screams in my head that override everything.

It is intrusive "eat this, keep eating that, what is for eating next, what can I eat, I have to eat, what is there to eat, oh can we eat this, there is something to eat there" thoughts racing around that never stop. Even if I do follow them and eat, they do not stop. And ignoring it, as I said, it's like holding out having to pee or trying not to sneeze, it is THAT strong and it never stops.

So my whole life. I could not for the life of me understand why people weren’t obsessed with food like I was. It was all I could think about. What I’m going eat, when I’m going to eat, every time I went to the store for soap, toilet paper, a birthday card - whatever - I would get a “treat”. It was exhausting and I was miserable.

40 mins of every hour thinking about food

Food noise is just that constant thinking about food. Planning meals hours or days in advance and obsessing over them. The inability to stop eating after a reasonable portion is another part of it, for me, at least.

food noise for was like an itch that needed to be scratched and I can’t think about anything else until I eat the food. Like if someone brought brownies to work, I’d try and try not to think about them and just stay busy but I would not be able to truly focus on anything until I gave in.

You know how some people say “I forgot to eat today”? I always thought those people are insane, as I constantly think about food

A constant fixation with food, thinking about future meals, feeling like I could still eat (mainly dessert) even though I just ate a healthy filling meal. A constant hankering for whatever got us gaining weight in the first place etc. I was properly addicted to sweets, and couldn’t get full until I’d eaten something sweet after every meal. The food noise was just the struggle to put off eating dessert … how many hours can I go without reaching for chocolate…. Can looking at cakes on insta fill me up without wanting to actually eat some? Just the constant mental calculations about how much longer I can put off a craving, or, the shame around how often I give in to a craving.

Walking by the pantry or through the kitchen and not being able to not open and grab something to snack on. It was also seeing a commercial on TV or online about some type of food and feeling the need to have that food. It was sitting at my desk at work and my brain telling me snack snack snack snack snack even if I wasn’t hungry. It was also my brain telling me I needed to eat everything on my plate every time. I’d absolutely stuff myself and not be able to stop because my brain would never tell me to stop eating- this was especially true when going out to restaurants.

I remember hearing people say they’re not a “sweets” person, or worse those who claim they “don’t like chocolate” thinking they must be aliens.

Every day is still a struggle. I’ve changed almost all of my eating habits, with an occasional treat within my weeklies, but I am always craving more food and especially fatty high point foods. It has taken a toll on my mental health at this point as it feels like I’m constantly restricting myself and thinking about food all the time (whether it be craving food, or making food, or meal planning) and it’s just exhausting.

I’ve been dieting since 5th grade. I’m now in my mid-30s.

I’ve never not had food noise

I've lost and gained weight my whole life. I've lost 100 lbs multiple times, and I can't say it's ever gone away.

Have you ever had a stressor in your life that was all you could think about? Maybe it was a project for work or school where you’d worry constantly about what you’d done, what you have left to do, waking up in the middle of the night thinking about. Maybe it was an event you were planning, like a wedding, where you worried about every last detail, wanting everything to be perfect. Maybe you have anxiety in general, where you can’t stop worrying about ALL. THE. THINGS. Well, food noise is similar. It’s not that I thought about eating all the time. I didn’t. I’d forget to eat all the time. It’s more like that internal anxiety dialogue but centered around food.

I could be doing ANYTHING—watching tv, emails—and what I wanted to eat would be running in the background. Like doing an inventory of what was in the pantry or fridge. I would think all day about what I wanted for dinner. That sort of thing. It’s awful.

Constantly obsessing over my next meal to the point where I couldn’t get things done.

I am constantly making deals with myself.

You can have that piece of cheese but you really need to buckle down at dinner and just have salad. And then shock of all shocks just a salad wasn’t enough so I’d break my bargain and hate myself all night and start thinking about my food budget for tomorrow.

The cycle of constant negative self talk is so toxic. It controls my life and made me a feel less than.

The constant thought about meals, snacks, treats, holidays, special dinners, what to make, how much to make, how much to eat, what's my limit, what will make me feel bad, what will make me feel good, what will other people like to eat, what is a good way to make food that is healthy, what isn't healthy, should I try a new recipe, what's delicious, eat out or delivery? eat in or delivery? how much to spend on food, how much is too much to spend on food, what's the difference between a healthy lunch and a lunch I really want, why am I still fat? Did I already eat? Is it time to eat again? Is it time to think about dinner? Did I take meat out of the freezer? Is it time to clean the kitchen/clean the fridge/organize the pantry? Should I make a cake? I love cake. We all love cake. I should make cake. What kind of cake? Mmm, cake. Ooo cookies! Oh, yeah I can't have Oreos. I love Oreos though. If I make coffee, I bet I could eat something sweet with it. It's relentless. On and on and on, an internal dialog related to food that never seems to go away.

Do you have food noise?

Four quick tests to see if this is putting a name to something you or a loved one is suffering with - Ask yourself:

1. On a scale of 1-5, What is your preoccupation with thoughts of food?

   (1) I never think about food - (5) I always think about food

   If you get 3-5 you likely are.

2. How soon after waking are you thinking about food?

   If you’re thinking about food before you leave your bed, you likely are suffering from food noise.

3. When was the last time you ate half your meal/dessert/plate and your body just rejected food - it just sent all the subconscious signals to tell you to stop eating?
   If the answer is not at some point in the last week - you are likely suffering from food noise.

4. When was the last time you didn't think about food and when you got hungry you literally had zero idea what to eat or what was in your fridge?
   If the answer is not at some point in the last week - you are likely suffering from food noise.

Conclusion

Is that heartbreaking to read? Well it was heartbreaking to hear, and even more so to revisit and write.

Next time you see some always shredded dude on TRT saying “If you’re hungry, drink a glass of water” make a mental note that they are full of it.

I hope this post gives you an ounce of empathy for those suffering.

At Uncivilized, but also at Patchwork, one of the things that we've done is really take a view on where are we now as humans in society, where were our grandparents at the same age, and what has changed?

One of the major changes in modern life has become the ubiquitous use of glyphosate in almost all crop farming in America and some in Europe.

Having dug into the science on the individual areas of the body from microbiome to liver health to neuro-energy, I've never really taken a whole body view of what is what glyphosate really does to someone.

My understanding, as I've told my parents many times before researching this post, was that glyphosate is bad because it suppresses good bacteria and it slows down your liver's detox system.

But, oh my god... It is so much worse.

Let's back up and then dive in.

What is Glyphosate and how is it used today?

Glyphosate is a broad-spectrum systemic herbicide and crop desiccant widely used in agriculture, horticulture, and various other applications. It was first introduced by Monsanto in 1974 under the trade name Roundup.

That's right, the Roundup that you buy from Home Depot and you spray on the weeds on your front lawn is the same glyphosate that is leaking into the water system and you are making the problem worse.

Glyphosate works by targeting a specific enzymatic pathway in plants to kill them.

The underlying crops that you want to use on are then genetically modified to be glyphosate resistant. So you primarily use it to kill weeds surrounding genetically modified crops.

“But I don’t eat GM crops”

And this is where it gets even more interesting. In the U.S., it's then used on non-genetically modified crops when they're ready for harvest. By killing them quicker and drying them out more rapidly, you can actually harvest grain from crops faster.

And as it's generally understood to not affect humans, there's no need to remove the glyphosate from the plants before they're used to produce food.

In Great Britain, it is approved for use until December 15, 2025 - most likely this will be extended, but glyphosate is expensive, and it's used much less in the U.K. due to its cost.

The global market size for Glyphosate was estimated at $10.92 billion in 2024

What are the health impacts of Glyphosate?

Whilst my original description to my parents around what Glyphosate does was not incorrect, it was simply incomplete. For too long, glyphosate has passed under the radar because the enzymatic pathway that is designed to affect it, which doesn't exist in humans.

However, if you look at acute issues or break down the actual systems in the human body, glyphosate causes havoc everywhere.

Cytotoxicity and Oxidative Stress

Research has demonstrated that glyphosate can induce oxidative stress and cytotoxic effects in mammals. This study examined the impact of glyphosate on human prostate epithelial cells, finding that exposure led to increased reactive oxygen species (ROS) generation and cell viability reduction.

Similarly, this study observed an antioxidant imbalance in human keratinocyte cells (HaCaT) upon glyphosate exposure, suggesting that oxidative damage is a key mechanism of glyphosate-induced cytotoxicity.

Gut Microbiome Disruption

The gut microbiota plays a critical role in human health, and emerging evidence suggests that glyphosate may disrupt microbial homeostasis.

This study highlighted that environmental pollutants, including glyphosate, alter the gut microbiome, potentially leading to metabolic disorders. Additionally, Krüger et al. (2013) found that glyphosate suppresses beneficial Enterococcus species, which play a role in inhibiting the proliferation of Clostridium botulinum (the cause of botulism), a harmful pathogen.

Such alterations in gut microbial balance could have far-reaching health consequences, including immune dysregulation and inflammatory diseases.

Liver Toxicity and Metabolic Disorders

Glyphosate exposure has been linked to liver toxicity and metabolic disturbances. This study reported an association between glyphosate excretion and the severity of liver fibrosis in patients with fatty liver disease.

Similarly, this study demonstrated that glyphosate exacerbates non-alcoholic fatty liver disease (NAFLD) in mice fed a Western diet, suggesting a potential synergistic effect between diet and glyphosate in metabolic disorders.

Carcinogenic Potential

The carcinogenicity (cancer causing ability) of glyphosate remains a contentious issue in scientific and regulatory discussions. While the International Agency for Research on Cancer (IARC) classified glyphosate as "probably carcinogenic to humans," regulatory agencies such as the European Food Safety Authority (EFSA) have contested this classification.

Zhang et al. (2019) conducted a meta-analysis and found a significant association between glyphosate exposure and increased risk for non-Hodgkin lymphoma, adding to the growing concern over glyphosate's role in cancer development.

Endocrine Disruption and Reproductive Health

Glyphosate has also been implicated in endocrine disruption and reproductive health issues. This study reviewed the pleiotropic effects of glyphosate exposure, noting its potential to interfere with hormone signaling pathways, leading to reproductive and developmental toxicity.

The study underscored the herbicide's capacity to disrupt estrogenic activity, which may contribute to adverse reproductive outcomes in both males and females.

Neurological Implications

There is emerging evidence that glyphosate exposure may contribute to neurological dysfunction. This study hypothesized a link between glyphosate and celiac disease, proposing that glyphosate's impact on gut microbiota could indirectly influence neurological health.

While direct neurotoxic effects remain underexplored, the disruption of gut-brain axis signaling due to glyphosate exposure warrants further investigation.

Repeatedly we see people with no genetic predisposition to gluten intolerance having awful experiences when they eat gluten. Without gluten degrading bacteria in your gut (killed off by glyphosate), no human is evolved to digest such a large gluten load.

Hepatic Antioxidant System Disruption

This study demonstrated that glyphosate disrupts the hepatic redox balance by upregulating metallothionein I and II gene expression, suggesting an adaptive response to oxidative damage.

Their findings indicate that antioxidants such as quercetin may mitigate glyphosate-induced hepatic damage, highlighting the potential for dietary interventions in reducing its toxicity.

Microbial Degradation and Environmental Persistence

While microbial degradation of glyphosate is a natural mechanism to reduce environmental contamination, its breakdown products, such as aminomethylphosphonic acid (AMPA), raise additional concerns.

This study reviewed microbial degradation pathways, noting that some glyphosate metabolites may persist in the environment and contribute to long-term health risks through bioaccumulation.

Conclusion on health

The cumulative evidence suggests that glyphosate exposure poses multiple health risks, including oxidative stress, gut microbiome disruption, liver toxicity, carcinogenicity, endocrine disruption, and potential neurological effects.

While regulatory agencies continue to debate its safety, the breadth of scientific findings highlights the necessity for stringent risk assessments and further research into its long-term effects.

Given the widespread use of glyphosate in modern agriculture, you should consider precautionary approaches to minimize exposure and explore safer alternatives.

How am I or my family exposed?

Luckily, as this is an issue that many nonprofits are increasingly frustrated by, there's been pretty widespread testing on glyphosate exposure in the food and environmental systems.

Every single study that has measured for glyphosate residues in human urine has found it.

Water

In June 2022, the U.S Centers for Disease Control and Prevention (CDC) published a massive study that showed more than 80% of urine samples drawn from children and adults in a US health study contained glyphosate.

Permitted levels in tap water reach 700 ppb in USA, and are at 10 ppb in the European Union.

Among 85 tap water samples analyzed by Moms Across America and Sustainable Pulse, glyphosate was found in 35 cases at levels up to 0.3 ppb.

In other tap water samples taken in the U.S. and the EU glyphosate residues were also low, which seem to rule out tap water as a major glyphosate exposure route, at least in these regions. (I’ll still be filtering my water though.)

Food

Glyphosate is regularly sprayed on more than 70 crops, including wheat, oats, barley, almonds, apples, dry edible beans, lentils, chickpeas (garbanzo beans), peas, grapes, rice, and sunflowers. Honey is also regularly contaminated.

The U.S. FDA tested for glyphosate for the first time in a small range of products in 2016, these included corn, soybeans, eggs and milk. The results showed that glyphosate was found at high but ‘legal’ levels in soybeans and corn but not in eggs or milk.

Independent studies found glyphosate in a wide range of products being sold at U.S. grocery stores including cereal, pea protein, bread and pulses. The majority of samples that tested positive had levels between 10 ppb and 1500 ppb.

UK government testing for glyphosate residues in bread showed frequent glyphosate contamination, sometimes exceeding 500 ppb in wholemeal bread.

Analysis of 69 honey samples from different origins revealed glyphosate at unexpectedly high levels, around 64 ppb. Some samples were contaminated with 163 ppb, a concentration neurotoxic to honeybees.

Mitigation Strategies

To reduce exposure to glyphosate and support detoxification:

1. Choose organic foods when possible. (ESPECIALLY OATS)

2. Thoroughly wash fruits and vegetables.

3. Support liver health with antioxidants like vitamin C and E.

4. Consider supplements that may help bind glyphosate in the GI tract, such as humic acid or chlorella.

Conclusion

The more papers I read and the more I wrote about this topic, the angrier I got. If you like me are surprised that this wasn't told to you or fully explained to you, now is your opportunity to tell others.

Eating organic foods isn't necessarily a granola thing to do anymore. I think you can probably get away with not choosing organic foods that are whole and have skins, but if you're choosing things like bread, grains, oats, you owe it to yourself to try and find organic.

Wild that this is another thing I have to be concerned about when my grandparents grew up without any of these issues.

As I looked down at my morning coffee and the daily supplement stack I'm taking over the Christmas break, a family member of mine said, "Why do you bother taking that when it just makes really expensive pee?"

And I thought to myself: "Every one of these pills has a very specific purpose that I am trying it out for."

But I do know many people that take things just because the internet told them to, especially multivitamins. Which, as a side note, are usually full of junk and the cheapest versions of any vitamin you're looking for.

So I wanted to dig into the actual science that taking multivitamins or a whole bunch of supplements might literally just make your pee really expensive.

At Patchwork, we generally do not advise anybody takes an actual multivitamin. And if we make supplement recommendations, they come with very specific needs. They have to show the result we're looking for, otherwise we tell someone to stop.

While it's true that excess water-soluble and fat-soluble vitamins are excreted in urine, the overall value of multivitamins depends on various factors.

Let's dive in.

Nutrient Absorption and Excretion

Multivitamins can indeed lead to brightly colored urine, particularly due to B vitamins (Riboflavin in particular). However, this doesn't mean the vitamins are entirely wasted:

- Your body absorbs what it needs and excretes the excess.

- The presence of vitamins in urine doesn't negate their potential benefits before excretion.

Potential Benefits

Research on multivitamin efficacy has yielded mixed results:

- Some studies suggest benefits for certain groups, such as reduced cancer risk in men and improved memory in older adults.

- Multivitamins may help fill nutritional gaps, especially for those with poor diets or increased needs.

Limitations and Controversies

The value of multivitamins for the general population is debated:

- Several large-scale studies found no significant benefits for heart disease, cancer prevention, or overall mortality in healthy adults.

- The U.S. Preventive Services Task Force concluded there's insufficient evidence to recommend multivitamins for primary disease prevention.

Considerations for Use

Whether multivitamins are worth taking depends on individual circumstances:

- They may be beneficial for pregnant women, older adults, or those with specific nutritional deficiencies.

- For most healthy individuals eating a balanced diet, multivitamins may not provide significant additional benefits.

Expert Opinions

Views on multivitamin use vary among health professionals:

- Some experts argue that a healthy diet should provide sufficient nutrients without supplements.

- Others suggest multivitamins can serve as a nutritional "insurance policy".

Excess is fine though right?

Wrong.

Unfortunately, because of the way that scientific and nutritional knowledge is laundered through medical education, there is a shared opinion that any excess vitamins are harmless and will just be filtered out of your body.

What this view fails to appreciate is that to be filtered out of your body, it actually needs to use your liver, your kidneys, and your existing detox pathways to do so.

As I covered earlier in "Your body (fat) is polluted", most of our detox pathways and the organs that we use for filtering out toxins are overwhelmed in a modern environment.

I personally have several friends who have suffered as adults from hypervitaminosis A. Clinically speaking, this can only happen when someone takes too much vitamin A from supplementation.

But that isn't the reality. Every person I know who had a cascading health failure from having too much vitamin A in their body didn't take supplemental vitamin A or a multivitamin.

Furthermore, the science which says that excess vitamins will just be excreted from your body is decades old and doesn't apply to people in their context today.

In addition, as mentioned at the beginning of this post, the ingredients which manufacturers use to make multivitamins are not the best, most bioavailable, or high-quality forms of those vitamins.

There seems to be no regulation over how much of each vitamin should or can be put in a pill.

Conclusion

While vitamins can lead to nutrient excretion in urine, dismissing them entirely as "expensive pee" overlooks potential benefits for certain individuals.

I think taking the opinion that broad spectrum vitamins someone is taking is expensive pee is actually a healthy one.

The decision to take vitamins should be based on individual nutritional needs, and the first line of action is always to get them from food.

The second being to only try and supplement the specific vitamins that you think you need and of the highest quality.

I always grew up hearing something about cortisol and how stress can make you gain weight but never really heard anyone explain it to me in a way that made sense.

So I dove in.

As it turns out there is substantial evidence linking stress to weight gain and obesity and some very well documented mechanisms of action.

Several mechanisms contribute to this relationship:

Hormonal Changes

Stress triggers the release of cortisol, a hormone that plays a crucial role in the body's stress response. Chronically elevated cortisol levels can lead to weight gain through multiple pathways:

• Increased appetite and cravings for high-calorie, fatty, and sugary foods

• Slowed metabolism, making it harder to burn calories

• Promotion of fat storage, particularly around the abdomen

Behavioral Changes

Stress can alter eating behaviors and lifestyle habits:

• Stress eating or "emotional eating" of comfort foods

• Decreased physical activity and exercise

• Disrupted sleep patterns, which can contribute to weight gain

As a side note - anecdotally - I mostly have my food, health, hunger and food noise dialled in/solved, but if I have a bad nights sleep - my hunger is unending.

Cognitive Impact

Stress interferes with cognitive processes that are important for maintaining a healthy weight:

• Reduced self-regulation and executive function

• Impaired decision-making regarding food choices

Research Findings

Several studies have demonstrated the link between stress and weight gain:

• A study of over 5,000 Finnish men and women found that stress-related eating was associated with obesity in women

• Research showed that people with high cortisol responses to stress were more likely to snack in response to daily hassles

• A study of 619 adults found that chronic stress had a significant direct impact on food cravings and body mass index

• Hair cortisol analysis in over 2,500 older adults revealed that those with higher cortisol levels tended to have larger waist circumferences and higher BMIs

Vicious Cycle

Importantly, the relationship between stress and obesity can become a vicious cycle:

• Weight gain and obesity can themselves be sources of stress, particularly due to weight stigma, or challenges in losing weight

• This stress can then lead to further weight gain, perpetuating the cycle

While the evidence strongly supports a link between stress and weight gain, it's important to note that individual responses may vary.

Some people may lose weight under stress, while others gain weight.

However, for many individuals, managing stress appears to be an important component of maintaining a healthy weight.

Additionally - for those who seem to lose weight under stress (like bodybuilders prepping for a show) - the weight lost, seems to reappear at lightning speed when the competition date passes, suggesting that stress does win out in the long run.

Stress management

Look, everyone's hard is hard.

And I can't possibly write a monologue lecture at the end of this post on how you should be managing your stress.

What I can say is that for me personally, exercise both gives me energy and lowers my overall stress. As does being in nature, eating well, nasal breathing, sauna, journalling and spending time with my family.

I have worked in some insanely stressful environments, usually around and caused by some very stressful people.

It took years for me to take my stress seriously and then when I did, years of experimentation to find what worked for me.

Even if you think that you are not stressed, just entertain the possibility that you're more stressed than you should be. And go on a fact-finding/experimentation adventure to find out what will help you manage that.

I can assure you that none of it will be a waste of time.

Breathwork - that weird, slightly pretentious term that for some reason I have always grimaced at, might actually play a crucial role in metabolism and thus, weight loss.

You've probably heard of Wim Hof (which raises body oxygen) or Box Breathing (which lowers stress), but less likely have heard of the long studied Buteyko breathing which raises blood carbon dioxide via the nose (nasal breathing).

Several scientific studies have explored the link between different types of breathing and metabolism, and suggest that nasal breathing may have positive effects on metabolic rate and related physiological processes.

The cliff notes mechanism is that by raising CO2 tolerance and thus CO2 in the blood, you actually create a space for your body to use more oxygen and thus energy.

Impact on Resting Metabolic Rate

A recent study published in 2024 investigated the impact of nasal breathing on resting metabolic rate. The research suggests that nasal breathing plays a role in modulating resting metabolism, affecting energy expenditure and metabolic efficiency.

While the study is still ongoing, preliminary analysis indicates a possible link between nasal breathing and resting metabolic rate (RMR), emphasizing the overlooked role of nasal respiratory physiology in energy balance.

The tricky thing to point out here is that to easily breathe through your nose requires a low-inflammation state. Those suffering from obesity are typically in a high inflammation state and as such we would expect to see them with a lower rate of nasal breathing.

However - we also would expect for the most part someone suffering from obesity to have a suppressed but higher metabolic rate.

In this study they actually found a tight correlation between the increase in nasal breathing and metabolic rate which both changed after having surgery to fix their nasal passages. Cool Right!?

Oxygen Utilization and Fat Burning

Following on on what the mechanism described in the intro it’s then unsurprising to learn nasal breathing has been found to be more efficient than mouth breathing in terms of oxygen supply and utilization in the human body.

This increased efficiency can lead to:

1. Enhanced oxygen uptake: Nose breathing imposes approximately 50% more resistance to the airstream than mouth breathing, resulting in 10-20% more oxygen uptake.

2. Improved fat burning: The more oxygen our bodies use, the more fat we can potentially burn.

Fats are large molecules made up of oxygen, carbon, and hydrogen.

When the oxygen we breathe reaches these fat molecules, it breaks them down into carbon dioxide and water (fat oxidation).

The blood then picks up the carbon dioxide – a waste product of our bodies – and returns it to the lungs to be exhaled.

Metabolic Regulation and Weight Loss

Several mechanisms have been proposed for how nasal breathing might influence metabolism and weight loss:

1. Parasympathetic activation: Nasal breathing stimulates the parasympathetic nervous system, which is associated with better metabolic regulation and fat-burning processes.

2. Nitric oxide production: The nose is a reservoir for nitric oxide, an essential gas that plays a central role in dilating airways and improving oxygen transfer.

3. Improved sleep quality: Nasal breathing can reduce the risk of sleep apnea and snoring, leading to better sleep patterns. Quality sleep is vital for weight management and metabolic regulation.

4. Enhanced exercise efficiency: Better oxygenation through nasal breathing can lead to more energy and stamina during workouts, potentially contributing to more effective weight loss efforts.

Physiological Effects

A study on the effects of different nostril breathing patterns showed interesting metabolic changes:

• Right nostril breathing led to a significant 37% increase in baseline oxygen consumption.

• Left nostril breathing resulted in a 24% increase in baseline oxygen consumption.

• Alternate nostril breathing caused an 18% increase.

These changes suggest that controlled nasal breathing techniques can influence metabolic rates.

While these studies provide intriguing evidence for a connection between nasal breathing and metabolism, it's important to note that more research is needed to fully understand the mechanisms.

My Anecdotes

As an amateur competitive cyclist who lives a mile above sea level (20% less oxygen) who does one competition every year at even higher altitudes with even lower oxygen, the idea that a change in my breathing patterns at rest and when I exercise could increase my performance is really compelling.

The amateur part means that in an 80/20 world, I've already picked up my newbie gains, and it is increasingly difficult for me to find the time to become more productive on the bike.

And so in no scientific way at all I have implemented the steps detailed below and have found that I can do workouts that previously would've had me gasping for air on my bike in training.

I can successfully breathe through my nose the whole way through intervals and feel that I also physically recover much quicker.

The steps taken and the performance gains found seem to compound.

I've since found that I mouth-breathe during sleep much less and as such my quality of sleep goes up (we’ll discuss HIF-1 and why this happens another time).

Ways to implement

I'm not going to give you an Andrew Huberman super complex protocol.

That's going to stress you out every single day. I'm going to break this down into two really simple things you can do.

Firstly, you can test your existing carbon dioxide tolerance by doing the test below.

I would recommend that you do it a couple times over a few days, average the result and write it down then test this every month or every year etc to see if you are making progress.

(Note that the results will vary at different altitudes - mine is double at sea level compared to Denver)

Test

When you are casually walking somewhere (not rushing), follow your breath, but after an exhale hold your breath and continue walking.

Count how many steps you can take before you physically need to gasp for air.

Test done. Don't repeat the test immediately after having done the test. You'll need a couple of minutes to recover, even if it doesn’t feel like it.

Ways to increase nasal breathing

Easy Buteyko breathing

There are entire courses you can take to get good at Buteyko breathing. I don't want to recommend that to you.

Fundamentally, I would recommend trying this 6 minute video

and then getting used to doing a control pause

every now and then, where if you're waiting for an Uber or if you're waiting for a flight or if you're in bed waiting for your partner to join, go ahead and try one.

Nose widgets

I have a bunch of these lying around the house, and I wear one when I'm in the sauna, when I'm exercising, when I'm walking the dog, or if I'm doing a hike. If I, for some reason, feel exceptionally out of breath or mouthy, then I'll wear one during the day too.

Plus the other parents at my kids’ daycare think I have a nose ring somedays so they’ll know not to mess with my kid.

What surprised me was that the conversation was with several people who are very intentional about their health, including a PhD.

I don't know if this PhD was having a bad day, but me suggesting this seemed to really trigger him. He was not interested in seeing any of the evidence I was referring to and simply told me I was lying.

In the last Uncivilized post, I briefly explored some of the high-level mechanistic evidence for this link between protein and insulin resistance.

Some of those studies were done decades ago. So I wanted to do a full post exploring what really is the modern association between these two things and any conclusions we can draw from it.

Fundamentally, at a high level, the critical thing that we need to understand is that people suffering from obesity are in a protein-sparing mode.

They are carrying abundant additional energy stores, and at Patchwork we line them up so that their body can to tap into those excess energy stores and not catabolize any protein or muscle as you lose weight.

This also means that they do not need to be eating one gram of protein per pound of body weight, especially as we don't recommend people suffering from obesity for doing excessive exercise, thus lowering protein needs further.

Insulin resistance is a condition where cells in the body's muscles, fat, and liver don't respond effectively to insulin.

If you want to go down a 🐰 hole on all the chronic illnesses which stem from insulin resistance. This is a great book.

So Does Protein Cause Insulin Resistance?

The relationship between protein intake and insulin resistance has been a topic of significant debate within metabolic research.

While protein, particularly in the form of branched-chain amino acids (BCAAs), is essential for numerous physiological processes, recent studies suggest it may play a nuanced role in metabolic dysfunction.

Insulin resistance, a hallmark of type 2 diabetes and obesity, appears to be influenced by dietary protein composition and metabolic pathways involving amino acids such as leucine, isoleucine, and valine.

Early research demonstrated that elevated plasma amino acid levels, especially BCAAs, were correlated with hyperinsulinemia in individuals with obesity.

This finding highlighted the potential for protein-derived amino acids to modulate insulin secretion and sensitivity.

Subsequent studies have expanded on this by examining the role of BCAA metabolism in the etiology of insulin resistance. For instance, this study underscored that impaired BCAA catabolism in obesity could lead to toxic accumulation of BCAA metabolites, exacerbating insulin resistance and systemic inflammation.

Mechanistically, BCAAs have been shown to influence key metabolic pathways that drive insulin signalling.

A study in 2016 revealed that a BCAA-derived metabolite, 3-hydroxy-isobutyrate, promotes vascular fatty acid transport, linking BCAA metabolism to ectopic lipid accumulation—a critical factor in insulin resistance. Furthermore, Fontana et al. (2016) demonstrated that dietary restriction of BCAAs could ameliorate metabolic health, improving insulin sensitivity and glucose tolerance.

The adverse metabolic effects of excessive protein intake, particularly from diets high in animal protein, have also been highlighted.

Kevin Hall observed that ketogenic diets, often rich in animal protein, increase circulating BCAAs and lipid intermediates, which can impair insulin signaling.

Similarly, this study in 2021 identified isoleucine and valine as the primary mediators of BCAA-induced insulin resistance, implicating these amino acids in the worsening of metabolic health.

But, not all studies support a direct causal role for dietary protein in insulin resistance. Solon-Biet argued that the effects of protein on insulin sensitivity depend on the balance of dietary macronutrients.

The insulin resistance research suggested that protein-induced insulin resistance may be mitigated by reducing overall caloric intake or by achieving a more favorable balance between protein and carbohydrate consumption. This highlights the complexity of dietary interactions and the insulin resistance influence on metabolism.

On a molecular level, excessive dietary protein may lead to nutrient signalling dysregulation via the mTOR pathway, a key regulator of cell growth and metabolism.

Back in 2014 Lynch and Adams emphasized that chronic mTOR activation by BCAAs might desensitize insulin receptors, impairing glucose uptake.

This aligns with the findings of Ramzan, who demonstrated that reducing BCAA levels through dietary intervention improved metabolic parameters in individuals at risk of type 2 diabetes.

Interestingly, plant-based protein sources, which are typically lower in BCAAs, appear to have a more favorable effect on insulin sensitivity.

This study in 2022 noted that diets emphasizing plant proteins might reduce systemic BCAA levels and improve metabolic health. This aligns with growing evidence supporting the role of plant-based diets in mitigating insulin resistance and associated metabolic disorders.

The role of protein in insulin resistance may also vary depending on the metabolic context.

Bloomgarden highlighted in 2018 that while high-protein diets might exacerbate insulin resistance in individuals with preexisting metabolic dysfunction, they can also promote weight loss and improve glycemic control in certain populations.

This superposition underscores the need for personalized dietary recommendations based on individual metabolic profiles.

In conclusion

While protein itself does not universally cause insulin resistance, excessive intake of BCAAs and animal-derived protein, particularly in the context of obesity and high-fat diets, may contribute to metabolic issues.

As covered in my last post about protein needs - high protein diets are generally great for athletes and lean aging populations who are concerned about sarcopenia.

But if you are overweight, massive animal protein intakes can be one of the things blocking your fat loss and gumming up your metabolism.

Finally - I am not here to take away your meat or keto diets. I love meat. Hell I buy a cow every year and this year slaughtered my own thanksgiving turkey. I’m just saying there are some things to consider here - More Protein does not equal More Fat Loss.

Bibliography

• Bloomgarden, Z. (2018). Diabetes and branched-chain amino acids: What is the link? Journal of Diabetes, 10(5), 350–352. https://doi.org/10.1111/1753-0407.12645

• De Bandt, J.-P., Coumoul, X., & Barouki, R. (2022). Branched-Chain Amino Acids and Insulin Resistance, from Protein Supply to Diet-Induced Obesity. Nutrients, 15(1), 68. https://doi.org/10.3390/nu15010068

• Felig, P., Marliss, E., & Cahill, G. F. (1969). Plasma Amino Acid Levels and Insulin Secretion in Obesity. New England Journal of Medicine, 281(15), 811–816. https://doi.org/10.1056/NEJM196910092811503

• Fontana, L., et al. (2016). Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health. Cell Reports, 16(2), 520–530. https://doi.org/10.1016/j.celrep.2016.05.092

• Hall, K. D., et al. (2021). Effect of a plant-based, low-fat diet versus an animal-based, ketogenic diet on ad libitum energy intake. Nature Medicine, 27(2), 344–353. https://doi.org/10.1038/s41591-020-01209-1

• Jang, C., et al. (2016). A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nature Medicine, 22(4), 421–426. https://doi.org/10.1038/nm.4057

• Lynch, C. J., & Adams, S. H. (2014). Branched-chain amino acids in metabolic signalling and insulin resistance. Nature Reviews Endocrinology, 10(12), 723–736. https://doi.org/10.1038/nrendo.2014.171

• Ramzan, I., et al. (2020). A Novel Dietary Intervention Reduces CInsulin resistanceculatory Branched-Chain Amino Acids by 50%: A Pilot Study of Relevance for Obesity and Diabetes. Nutrients, 13(1), 95. https://doi.org/10.3390/nu13010095

• Solon-Biet, S. M., et al. (2019). Branched chain amino acids impact health and lifespan indInsulin resistanceectly via amino acid balance and appetite control. Nature Metabolism, 1(5), 532–545. https://doi.org/10.1038/s42255-019-0059-2

• Vanweert, F., Schrauwen, P., & Phielix, E. (2022). Role of branched-chain amino acid metabolism in the pathogenesis of obesity and type 2 diabetes-related metabolic disturbances. Nutrition & Diabetes, 12(1), 35. https://doi.org/10.1038/s41387-022-00213-3

• White, P. J., et al. (2021). Insulin action, type 2 diabetes, and branched-chain amino acids: A two-way street. Molecular Metabolism, 52, 101261. https://doi.org/10.1016/j.molmet.2021.101261

• Yu, D., et al. (2021). The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. Cell Metabolism, 33(5), 905-922.e6.https://doi.org/10.1016/j.cmet.2021.03.025

In a world where everybody steals each other's content and keeps re-hypothecating and handing it off as their own, it's easy to see how it became so ubiquitous that everybody thinks you need 1 gram of protein per pound of your body weight every single day to avoid wasting away.

This is the core message of every health video on tiktok.

But I'm here to tell you that there is no scientific backing to this idea.

It is absolute bullshit.

And what's worse is that if you are overweight or obese, eating that much protein could actually prevent you from losing fat.

I'll say it again for those guys in the back: eating too much protein can actually prevent you from losing fat.

This idea was extremely hard for me to personally accept having been on a long ketogenic journey that ended with over a year of being a hardcore carnivore and consuming, on some days, up to 300g of protein.

In this post we’re going to explore the science around:

• How much protein do you need (when strength training)

• Can protein prevent you from losing fat

Let's dive in.

What does the science say about how much protein you should eat when working out?

Note - I specifically only looked at and compared studies that use the same meal frequency because that in and of itself can effect total muscle protein synthesis.

Strength training places substantial physiological demands on the body, necessitating adequate protein intake to support muscle repair, hypertrophy, and overall performance.

While recommendations on protein requirements have evolved, the interplay between dietary protein and strength training continues to be a subject of robust scientific inquiry.

Protein Requirements in Novice Strength Trainers

Early research showed that beginners in strength training need much more protein than people who don’t exercise. One study found that around 0.7 to 0.8 grams of protein per pound of body weight per day is ideal for building muscle and strength when starting out.

This is because your body is working hard to adapt to the new demands of training.

Impact of Protein Supplementation on Muscle Gains

Adding extra protein to your diet can help you get stronger and build muscle depending on where you are starting form.

A meta-analysis of studies found that getting more than 0.7 grams of protein per pound each day lead to no noticeable improvements in muscle and strength.

Short-Term Protein Intake and Recovery

What about after a workout?

A study found that eating a lot of protein (1.3g per pound of bodyweight) right after lifting weights had no effect in recovery and reduce soreness.

The control group, eating 0.8 grams of protein per pound daily after workouts worked the same for recovery and soreness.

Dose-Response Relationship and Muscle Strength

Another meta-analysis of randomized controlled trials in 2022 looked at how much protein helps the most with strength. They found that intakes up to 0.68 grams of protein per pound daily is the ideal range to build strength.

No enhancements above that level were identified

Everyone’s body is a bit different, though, so some people may need more or less. The drum of “Protein, protein, protein” was originally more likely for your grandmother than for you.

Evaluating Protein Needs in Trained Athletes

If you’ve been training for a while, your body gets better at using protein.

One study found that strength athletes might only need about 0.63 grams of protein per pound daily, which is a bit less than what beginners need.

When they upped this to 1g per pound of bodyweight they found no increase in strength but a marked increase in protein oxidation (using protein as energy).

I’m pretty sure we’re all being lied to.

Influence of dieting on Protein Requirements

What if you’re dieting? A study found that when you’re eating fewer calories, you need do need more protein to keep your muscle mass. But not as much as you think.

At 0.36g of protein per pound, they found that athletes losing muscle in a caloric deficit (as measured by urine nitrogen balance) BUT at 0.72g per pound, that athletes were gaining muscle in a caloric deficit (as measured by urine nitrogen balance).

Note: The calorie intake of each person was 8.1kcal per lb of bodyweight and this study only ran for week (that would be ~1370kcal for me).

This means that if you’re cutting weight, paying attention to protein becomes even more important, but again - you don’t need 1g per pound.

The Role of Protein Quality

Not all proteins are equal. High-quality protein sources like whey, eggs, and meat have amino acids your muscles need the most.

If you find yourself eating a lot of plant protein you will likely need to up it. All of these studies used animal sources of protein like whey, eggs, and meat.

These are especially good at triggering muscle growth.

Practical Applications for Strength Trainers

Based on all this research, most people who lift weights do best with 0.7 grams of protein per pound daily. Splitting your protein evenly across meals and eating some after workouts can make a big difference. Adjust these numbers based on your goals, like losing weight or gaining muscle.

Notes on nuance for strength trainers and non strength trainers

Can you gain more muscle eating more than 0.7 grams of protein per pound daily? Yeah, probably!

There are studies that say that, but they didn't stand up to the criteria that I would want to include them in this review. I think that they say that there is diminishing returns past 0.7 grams but returns no less up to 1.3 grams per pound.

The key takeaway is that if you're obsessed over one gram per pound every single day, and you get to 9:00 pm, and you’re at 0.7 grams, you should not be fretting about it.

Two other things to call out here are:

Firstly, these were somewhat young strength-trainers. As you go over this literature and the larger body of literature, you end up seeing this paradox - the key way to maintain muscle is with resistance training, but also resistance training means you have higher protein turnover and thus require more protein.

If you are in the 20% body fat range (for men) doing hours in the gym + cardio and running an energy deficit then by all means - push for the 1.3g/lb you likely do need it due to protein turnover and the biological limit to which you can release fat from your fat cells to burn.

Secondly, age plays a role in muscle protein synthesis(MPS). If you are a man in your late 30's and above, you will have higher protein needs because you need more dietary protein to stimulate muscle protein synthesis and maintain your skeletal muscle which is essential for longevity. The 1g/lb guidance can put you on the safe side, although timing & making sure you are maximising MPS may be more important.

What does the science say about protein intake and weight loss prevention?

Saying that a protein intake if you are overweight may keep you overweight, will get you a lot of heat. Trust me I know. But it would be unethical not to point out some of the evidence available in the space, and also note that it is a very under-researched area that I hope we research more in the future.

I'm not saying this is 100% categorically correct for every single person who is overweight.

I am saying that there is evidence that there is a mechanism whereby a high protein intake can make somebody insulin resistant, and thus resistant to fat loss.

And that several people on the internet have had success in restricting their protein intakes in certain ways, thus allowing them to lower blood glucose and lose body fat. Let’s dive in.

There are 3 critical papers to look at to get this picture:

1. Plasma Amino Acid Levels and Insulin Secretion in Obesity

This study, published in the New England Journal of Medicine, looked at insulin and amino acid levels in obese and non-obese individuals.

It found that obese individuals had higher circulating levels of branched-chain amino acids (BCAAs).

Moreover, the study reported that “the concentration of each of the amino acids elevated in obesity correlated directly with serum insulin.”

This correlation is significant because elevated serum insulin levels are a hallmark of insulin resistance, which can hinder fat loss. High circulating BCAAs may exacerbate this issue, contributing to a metabolic state that makes it more difficult for obese individuals to lose fat.

2. A Novel Dietary Intervention Reduces Circulatory Branched-Chain Amino Acids by 50%: A Pilot Study of Relevance for Obesity and Diabetes

This pilot study demonstrated that restricting dietary intake of BCAAs led to a 50% reduction in circulating BCAA levels within just seven days.

This rapid response suggests that dietary manipulation can significantly influence metabolic markers associated with obesity and insulin resistance.

Lowering circulating BCAAs could potentially mitigate the insulin resistance observed in obese individuals, making it easier for them to lose fat.

While this study was a pilot, its findings are promising and warrant further exploration into the connection between dietary BCAA restriction and fat loss.

3. Restricting Branched-Chain Amino Acids within a High-Fat Diet Prevents Obesity

In this animal study, researchers compared the effects of three diets: a standard chow diet, a high-fat diet with added BCAAs, and a high-fat diet with restricted BCAAs.

The results were striking. Mice on the restricted BCAA diet exhibited lower serum glucose levels, lower insulin levels, and gained the least amount of weight compared to the other groups.

This study underscores the potential for dietary BCAA restriction to counteract the negative effects of a high-fat diet, particularly with respect to insulin resistance and weight gain.

While animal studies don’t always translate directly to humans, the findings align with the results of the pilot study mentioned earlier, suggesting a possible mechanism that could apply to human obesity as well.

The Bigger Picture

These studies collectively point to a mechanism whereby high protein intakes—specifically high BCAA intakes—can contribute to insulin resistance and hinder fat loss in certain individuals.

While the idea that reducing protein intake might aid weight loss is counterintuitive to many, these findings suggest it’s a hypothesis worth investigating further.

It’s important to note that these findings don’t apply universally. Protein is an essential macronutrient, and adequate intake is vital for overall health.

However, if you’re struggling with obesity and insulin resistance, particularly those consuming a diet high in BCAAs as social media tells you to do, this approach might offer a novel strategy for breaking through barriers to fat loss.

As research progresses, it’s crucial to approach this topic with an open mind and a willingness to challenge conventional dietary wisdom. By doing so, we may uncover new ways to solve our issues.

Final thoughts on protein on the whole

First and foremost - you do you. I am not telling anyone how to live.

In responding to someone stressing about eating 1g/lb this week on how it is unnecessary I clearly upset several people who had no interest in seeing the evidence for the claims, only to personally attack me. I didn’t help by insulting back. Funny thing was, the photo they dug up to disprove my position was taken when I was eating ~1.5g/lb - go figure.

Do I think you need to have any stress about hitting 1g/lb if you are active, no. Food should serve us, we don’t serve our food.

Do I think every coach should start their overweight clients at 1g/lb, also no. Not only is is wasteful — it could clearly be making them insulin resistant. I think you should see blood work first if anything (that’s what patchwork does).

Acknowledgements

Notable thanks to Menno Henselmans, Brad Marshall and Jeff Nippard for finding and sharing these studies and ideas in various forms.

One of my strongest-held beliefs that really kicked off my journey to try and decode obesity was the idea that hunger always exists for a reason.

Our bodies are wildly intelligent machines - so intelligent that for everything that happens in your body, there are a thousand feedforward and feedback systems.

It's just not acceptable to say our body does a thing because it we have a gene mutation that never had to be turned off before now (the thrifty gene hypothesis).

As you pursue this line of thinking that our body does everything for a reason, it leaves you questioning things like:

Why is it that we store such massive amounts of body fat?"

There is no evolutionary argument in which it makes sense to.

We as humans used to need to store up some body fat for the winter months, but actually, if anything, we evolved to be able to rapidly drop that body weight in the spring when it was essential we could move efficiently and with pace to hunt, gather, war, mate etc.

From what I've seen, if you are metabolically healthy and you eat completely organic, extremely clean whole foods, you can make yourself fat enough for the winter.

When you decide to stop overeating, your body weight will drop back to its normal baseline. This has been borne out in clinical studies where you can overfeed humans and they will gain weight (eating too much causes weight gain is actually a biological fact) but as soon as you stop overfeeding them, they will lose that weight and go back to baseline.

Overfeeding, by the way, is the condition where people are putting food in their mouth and forcing themselves to swallow it, but every cell in their body is screaming at them that they do not want to eat more food. Oddly enough, that seems to be a phenomenon which is happening rarer everyday today.

And so what is making us all so damn hungry?

Obesity is not caused by overeating or that you miscalculated your maintenance calories and put too many in.

“Calories In Calories Out is like a burrito: burrito in, burrito out. If you poop out more burrito than you eat, there's less burrito in you. First law of burritodynamics!”

Overeating is a result of our hunger signals telling us to eat. If we can find what would make us hungry, we might have a chance at cracking Obesity.

Let me say that again. Eating too much and gaining excessive body fat is the result, not the cause. Do not let people tell you that you gained weight because you have no discipline etc. Those people are ****ing idiots. You cannot beat your hormonal directive.

Having been on some version of a ketogenic diet for the better part of 8 years (which ended for me in January of this year), I used to say that hunger is primarily driven by sugar, carbohydrates, and insulin spikes.

I wouldn't listen to any person that said otherwise until one day I ate 4oz of honey with my morning coffee.

I barely finished it.

It wasn’t sickly like you’d imagine, I love sweet stuff, but as I got to the bottom of the glass I could almost hear the cells in my body screaming “PLEASE ****ING STOP”.

My hunger was gone. Nowhere to be found. I did not eat again til dinner. That was the first time in a long time, my brain just shut up about food for hours on end.

That, plus several other experiments and a ton of research that I've done subsequently, has led me to believe that our body is fundamentally hungry for one of four reasons:

1. It needs energy

2. It needs micronutrients

3. It needs to create fat

4. It is chemically dis-regulated

I will dig in to 1, 2 and 4 in later posts on uncivilized, but for now I want to dig in to this idea that our bodies make us hungry because they are TRYING to create fat.

(N.B. See the post on Seed Oils and Obesity - this is pertains to number 4)

Why would we want to make fat?

Well we’ve covered that it is an energy store (for winter/hibernation).

But as seen in a day of my ranting and dumping scientific studies on X this week.

There are toxins and pollutants in our environment which are lipophilic.

This means that they like to stick to fat particles as they travel through the body, and as such should be filtered out by the our livers, released into our bile and pooped out (if you eat the right things and poop regularly enough).

Now if you liver’s detox capacity is overwhelmed, and your liver cannot store easily store more toxins in it these pollutants will continue to float around your body in your blood doing damage.

Until they don’t…

And this is where I think you body may want you to create more body fat, to sequester these toxins out of your blood and into hibernation. By storing them in body fat, they are in no way inert, but they are for sure way less harmful.

Imagine body fat as a vault—a place where your body stashes things it can't easily get rid of. It’s clear it stores substances that don’t belong in our blood, particularly persistent organic pollutants, or POPs.

These pollutants—industrial chemicals like dioxins, PCBs, and other compounds that resist breaking down in the environment—enter our bodies through air, water, and food, and, thanks to their stubborn chemical structure, end up tucked away in our fat cells.

Unlike nutrients or excess calories, which we can eventually burn off or use up, POPs stay locked in that vault for years, if not decades, waiting for the day they’re released. And for many people, that day arrives when they decide to lose weight.

When you lose weight, you don’t just burn fat; you unlock this vault and unleash its contents back into your bloodstream. This release of stored pollutants isn’t just a neat biological quirk; it’s a critical health risk.

Studies have shown that losing body fat can increase the levels of POPs circulating in your blood, leading to a range of unexpected health issues. Imagine working hard to slim down, only to face an invisible consequence: a surge of chemical exposure your body thought it had safely stashed away.

Persistent organic pollutants are incredibly stable, meaning that once they're inside your body, they don’t degrade easily. This chemical stability is why they end up in fat cells; it’s the body’s way of quarantining these unwanted guests, keeping them away from vital organs.

Yet the process of losing weight disrupts this system. Rapid or substantial weight loss, especially through methods like bariatric surgery, can lead to an especially high release of these stored pollutants. This means that while weight loss can reduce cardiovascular strain and improve insulin sensitivity, it may simultaneously put you at risk for POP-related toxicity.

Something your body doesn’t want in its blood, back in the blood… Does that sound like a reason to slow your metabolism, make you hungry and gain back all that weight you lost? Hmm 🤔

So, what happens when these pollutants re-enter circulation? Studies suggest that they can interfere with metabolic processes and may actually counteract some of the metabolic benefits of weight loss itself.

For example, one review found that in individuals with type 2 diabetes, calorie-restricted diets might not produce the expected improvements in blood sugar regulation because POPs can impair insulin function. It’s like trying to clean a house while releasing hidden dust all over; even as the surface improves, new obstacles emerge.

POPs can even impact cognition, especially as they are mobilized from fat stores into the bloodstream. Research following the Look AHEAD study showed that some individuals experiencing weight loss also faced unexpected cognitive declines, and POPs were considered a likely factor . In other words, pollutants stored in fat could affect the brain when released, especially in cases of rapid weight loss.

For younger people and teens, this effect is just as concerning, if not more. In fact, a study on obese adolescents found that the release of POPs during weight loss can create unique risks for developing bodies, potentially impacting growth and metabolic regulation.

And while detox diets sound appealing, they don’t live up to the hype when it comes to dealing with POPs. Research shows fad “detox” or “liver cleanse” diets are largely ineffective in safely clearing pollutants from the body. Rather than offering a genuine solution, they might simply encourage further weight loss, thus releasing more stored POPs.

POPs and other lipophilic toxins pose a dilemma. We’re conditioned to think of weight loss as a straightforward path to health, especially in a society plagued by obesity.

Yet, if your fat is storing not just energy but also a backlog of chemical pollutants, slimming down becomes a double-edged sword.

Studies suggest that instead of merely focusing on weight loss, we need strategies that safely address POPs directly or focus on reducing their intake in the first place.

Well ain’t that depressing.

You lose a bunch of weight, and this stuff stays elevated in your blood for over a year unless you (very slowly) detox it, or you put it back in the vault by gaining the fat back.

But I don’t eat persistent organic pollutants

Whilst it is true that a person's persistent organic pollutant load has gone down in recent years due to legislation restricting the use of these chemicals in our environment, they are just one example of toxins that overwhelm our liver’s detox pathways (ALDH being the primary one).

In a world of processed food, fluoridated water, vitamin fortified foods, microplastics, “natural flavorings”, mold growth, amalgam fillings and excessive alcohol, it is reasonable to understand how our livers become overwhelmed.

Think of a leaky bucket under a running tap. If the leak gets gummed up, the bucket will start to fill and at some point the bucket is full and every seconds causes a spill. That is your liver in a modern environment.

Ask ChatGPT “What are key things foods Substances and habits in modern life that slow down the ALDH pathway in the liver” and here’s what we get:

Alcohol and Acetaldehyde Accumulation

• Alcohol itself is a significant inhibitor. After consuming alcohol, acetaldehyde builds up faster than ALDH can break it down, particularly in those with ALDH2 deficiency (common in East Asian populations).

• Alcoholic beverages often contain added chemicals or congeners (impurities), which can further burden the ALDH pathway.

• Seed oils (if eaten) as mentioned in my previous post are an enormous source of the aldhyde - 4-hydroxynonenal (Seed Oils = Alcohol in your liver)

So not just the alcohol, the additives we put in with it to make trulys and keep wine from spoiling.

Processed Foods and Additives

• Preservatives like sodium benzoate: Found in sodas, candies, and processed foods, these preservatives can inhibit ALDH activity, adding to the body's aldehyde load.

• Artificial flavorings and colorings: Common in packaged snacks and beverages, these additives create oxidative stress, indirectly overwhelming the ALDH pathway.

• Sugary and high-fructose corn syrup: These cause insulin spikes, which contribute to systemic inflammation and can indirectly impair ALDH function.

I have experimented with the honey diet, and peaty inspired ways of eating, which I do believe are mostly harmless if not beneficial (if your metabolism is unblocked) but the underlying insulin spikes themselves can be inflammatory and slow down ALDH - this is one of the most compelling reasons to avoid added sugar in my opinion.

Pollution and Environmental Toxins

• Airborne pollutants (e.g., formaldehyde and other aldehydes): Often inhaled in urban environments, these aldehydes can overwhelm the ALDH system.

• Cigarette smoke: Both firsthand and secondhand smoke contain acetaldehyde and other aldehydes, which can quickly exhaust ALDH enzymes.

• Industrial chemicals: Frequent exposure to chemicals in cleaning products, cosmetics, and plastics can increase the toxic burden on the liver.

I know someone who at the slightest smell of smoke would have a nervous breakdown and had to be taken to hospital. Turned out his liver was cooked. He also somewhat insanely, could not get below 20% bodyfat without screaming food noise and uncontrollable hunger (all solved since dealing with his liver issue).

Medication and Pharmaceuticals

• Paracetamol (acetaminophen): This common pain reliever depletes glutathione, a key antioxidant needed by the liver to support the ALDH pathway.

• Certain antibiotics and antifungals: Some medications, including metronidazole and certain antifungal drugs, inhibit the breakdown of aldehydes, taxing the ALDH pathway.

Fans of the show “Reacher” might be surprised to know that Alan Ritchson had to go on TRT (he was already jacked) after staying on paracetamol and NSAIDs for weeks on end which caused a hormonal mess originating in his liver.

Nutrient Deficiencies

• Low glutathione levels: Glutathione is essential for detoxification pathways. Poor diets, nicotine or high toxic loads can deplete it, slowing ALDH effectiveness.

• Vitamin B deficiencies (especially B2, B3, B6, and B12): These B vitamins play critical roles in liver function and detox pathways, including ALDH.

• Low levels of magnesium and zinc: Both minerals support detox pathways, and deficiencies can impair enzymatic function.

We all know our soil is depleted. The foods we eat today contain 1/10th of the nutrients our grandparents ate. To be nutrient deficient isn’t a whooshky idea - we likely all are. The CDC estimates 91% of American’s are deficient in at least one key nutrient.

Why this sticks for me

This idea is very sticky to me for a number reasons.

Self famed “rebound” experts seemingly focus on tampering our bodies’ natural immune response to fat loss, by narrowing in on the mechanisms of autoimmunity which turn on during a fat loss phase, but NEVER ask themselves

Why is the body having an autoimmune response to fat loss?

Seems like a no brainer question to ask. Maybe trying to overrule your bodies autoimmune response is essentially a really bad idea.

Your body is trying to protect you and keep you alive.

Another thing here is the role that exercise can play in detoxing.

It is known that we cannot directly tie energy “burned” in exercise to fat mass loss or total energy spent. We have strong theories and some maths that is correlated (but not that tightly). Even the constrained energy model, which I love, breaks for any random sampling of people.

But what does exercise do? Exercise liberates fat from stores, degrades organic pollutants in circulation, and increases sweat volume (a key detox mechanism).

Is the role of exercise in weight loss, actually not simply to burn calories, but to amp up detoxing our stored pollutants?

Our livers are collectively screwed and until we unscrew them every +1 pollutant will drive hunger and fat gain.

Your DNA matters

“Well they have good genetics” is mostly and asinine statement that removes agency from someone suffering from obesity.

However, your genetics do play a role.

Personally I have a combination of gene mutations which means my ALDH pathway is messed up (the key liver detox pathway) in addition to having a double MTHFR mutation which means more detox pathways are gummed up, and other mutations which on the whole means I need to eat the equivalent of 9 eggs day to function like a normal human being.

Good news bad news

The good news is:

• this is a scientifically proven model that can explain a major driver of obesity (or even just a little belly fat), that is separate from seed oils (for avoiders that are lacking progress)

• that when addressed can get hunger under control (it did for me) and leave you in a much healthier state ensuring not only weight loss, but no rebound weight gain.

• it is mostly cheap to solve

• no need to take experimental GLP-1 medication
  
  The bad news is:

• detoxing your liver and body fat can take years and lots of experimentation

• the NIH seems to want to ignore this glaringly obvious issue

weight loss medication that suppresses hunger (ozempic) is likely overpowering your bodies signals that you are toxic and slowing motility so you are reasbsorbing toxins in digestion

A place to start

So where do I start?
At a high level ask yourself if you have ever been exposed to a core toxin source?

Work forwards from there.

Do you have DNA results? What does your microbiome look like? How is your blood?

Do any of these statements actually make any sense:

Just eat less
Just fall sleep
Just wake up
Just move more
Just raise your blood sugar
Just be happy
Don't be sad
Just be more fertile
Just grow muscle
Just lower your blood sugar
Just calm down
Just don't be angry
Just don't be upset
Just increase your bone density
Just be less fertile

You can't unsee this

You cannot out think or out work your hormonal operating system.

Saying these bad foods contain this thing thus the thing is bad, is not in fact the argument against seed oils, and actually biscuits, cakes, and dressings are mostly inert if made with naturally occurring fats.

Then to mention the lipid heart hypothesis - jeez this was such a bad take.

I replied with a comprehensive explanation of the key devil in seed oils - linoleic acid - an Omega 6 pufa and the nuances in how to interpret the whole body of evidence that implicates the causal relationship of dietary linoleic acid in modern chronic disease.

A comprehensive explanation that, I believe should be shared here rather than get lost into the twitterverse. Sadly, where the seed oil discourse fails is that this information exists in blogs and substacks (like this), and not on the website for a bona fide organization such as the American Heart Association. (I am working on this and hope to change said situation soon).

Introduction

Linoleic acid is a polyunsaturated Omega-6 fatty acid that plays a crucial role in human health.

It is considered an essential fatty acid because the human body cannot synthesize it; it must be obtained through diet.

Linoleic acid sources in the diet include nuts, seeds, and some meats, but primarily come from seed oils such as corn, soybean, sunflower, peanut, safflower, canola, rapeseed, grapeseed, cottonseed and rice bran oil.

While linoleic acid is vital for maintaining the structure of cell membranes and is involved in the production of signaling molecules, excessive consumption or an imbalanced consumption in relation to Omega-3 fats leads to negative health effects.

In a modern day context virtually every person living in the USA and other western nations is consuming linoleic acid at an imbalance to Omega-3 fats whilst also consuming excessive linoleic acid.

Metabolism of Linoleic Acid

Once ingested, linoleic acid undergoes metabolism in the body through a series of enzymatic reactions. Initially, linoleic acid is converted to gamma-linolenic acid (GLA) by the enzyme delta-6-desaturase.

GLA is then converted into dihomo-gamma-linolenic acid (DGLA), which can further be metabolized to form arachidonic acid (AA).

These metabolites, particularly arachidonic acid, are precursors to various eicosanoids, which are signaling molecules involved in inflammation and immune responses.

Peroxidation of Linoleic Acid

Lipid peroxidation, on the other hand, is a process that occurs under pathological conditions and involves the oxidative degradation of lipids.

1. Initiation: The reaction starts when a reactive oxygen species (ROS) or a free radical removes a hydrogen atom from a lipid, particularly from the unsaturated fatty acids in the lipid bilayer of cell membranes, creating a lipid radical.

2. Propagation: This lipid radical reacts with oxygen to form a lipid peroxyl radical, which can then react with another lipid molecule, creating a chain reaction of lipid radical formation and leading to widespread membrane damage.

3. Termination: The chain reaction ends when two radicals react together or are quenched by antioxidants.

The result of lipid peroxidation is the formation of a variety of breakdown products, including aldehydes like malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), which is toxic to cells and contributes to the pathology of various diseases, such as atherosclerosis, neurodegeneration, and cancer.

It is critical to understand that 4-HNE can create pathological oxidative stress such that the ingestion of linoleic acid creates a peroxidation cascade that is self fulfilling.

By many accounts the peroxidation of linoleic acid and its breakdown products in a western diet context, is the primary source of oxidative stress on the body.

Negative Effects of Consumption

1. Inflammation: A high intake of Omega-6 fatty acids, namely linoleic acid, relative to Omega-3 fatty acids, promotes inflammation in the body.

2. Oxidative Stress: Linoleic acid is more prone to oxidation than saturated or monounsaturated fats. The oxidation products of linoleic acid are the main driver of oxidative stress in the body, and cause cellular damage.

3. Unstable Cell Membranes: The incorporation of linoleic acid into human cell membranes creates inherently unstable cells. For example, the current level of consumption is such that linoleic acid levels in LDL cholesterol are artificially higher and as such these LDL particles are now more prone to oxidation than historically normal (LDL particles require oxidation to become atherosclerotic).

Understanding The Science Behind Linoleic Acid

Understanding the harmful effects of linoleic acid requires not just reviewing isolated studies, but a comprehensive synthesis of all available evidence across different animal models (including humans) and timelines.

Without this holistic approach, it’s easy to cherry-pick short-term studies to dismiss the long-term risks.

The ongoing debate over saturated fats (SFAs), polyunsaturated fats (PUFAs), and seed oils will never reach a conclusion unless there is a recognition of the need to integrate animal studies with both short-term and long-term human trials.

Critics often point to trials lasting no more than 12 weeks to argue against the findings from animal research, while ignoring pivotal long-term studies, such as the 8-year LA Veterans Administration Hospital Study.

They overlook mechanisms and instead treat the observed effects in short-term trials as standalone facts, missing the larger picture that understanding these mechanisms is essential to contextualizing the results.

To synthesize the evidence effectively, we must consider the following mechanisms:

1. Ethanol Metabolism and Fatty Liver: Ethanol’s metabolism via CYP2E1 generates reactive oxygen species (ROS), damaging ApoB and preventing the export of hepatic triglycerides.

2. Choline and ApoB Lipidation: In non-alcoholic models, choline deficiency impairs the lipidation of ApoB with phosphatidylcholine, a critical step in preventing fatty liver.

3. Nutrient Impact on Fatty Liver: Adequate protein, sulfur amino acids, and choline intake can eliminate fatty liver caused by alcohol, sugar, or fat.

4. Oxidation of PUFAs vs. SFAs: PUFAs oxidize more rapidly than SFAs, increasing the choline requirement for exporting SFAs from the liver.

5. Liver Fat and NASH Progression: In non-alcoholic models, SFAs worsen liver fat compared to PUFAs, but PUFAs accelerate progression to non-alcoholic steatohepatitis (NASH) due to oxidative damage, which is a more critical factor in NASH than the SFA/choline ratio.

6. Alcoholic Models: In contrast, SFAs protect against liver fat in alcoholic models because oxidative damage to ApoB outweighs the importance of the SFA/choline ratio.

7. Human Trials: Short-term human trials mimic non-alcoholic animal models, with SFAs increasing liver fat and PUFAs reducing it.

8. Long-Term Effects: Over extended periods, PUFAs are predicted to exacerbate NASH progression, the true threat to liver health and longevity.

9. The LA Veterans Administration Study: This study revealed that the detrimental effects of PUFAs in humans become apparent only after more than 8 years.

In sum, to truly understand the risks associated with linoleic acid, it’s essential to grasp the full scope of studies and the underlying mechanisms, rather than relying on selective, short-term evidence.

He said he would get back to me

Involvement of Linoleic Acid in Obesity

When trying to decipher modern day obesity we need to appreciate that trials repeatedly show when we overfeed humans, through homeostasis their bodies return to baseline fat levels.

Obesity is driven by an external factor that is both increasing appetite beyond observable energy requirements and lowering a human’s metabolic rate.

The observable result, not cause, is an energy imbalance when measured through “calories in; calories out”.

Linoleic acid has emerged as a significant factor in the development of obesity, particularly through its influence on the endocannabinoid system.

The endocannabinoid system plays a crucial role in energy homeostasis, appetite regulation, and lipid metabolism, all of which are pertinent to the pathophysiology of obesity.

In recent years, the dietary shift towards increased consumption of linoleic acid, primarily through seed oils, has coincided with rising obesity rates globally. Understanding the biochemical and physiological mechanisms by which linoleic acid contributes to obesity is vital for developing dietary strategies and interventions to mitigate this public health issue.

Endocannabinoid System

The relationship between linoleic acid and obesity is mediated, in part, by the endocannabinoid system, which includes receptors such as CB1 and CB2, endogenous ligands like anandamide (AEA) and 2-arachidonoylglycerol (2-AG), and enzymes involved in their synthesis and degradation.

Linoleic acid serves as a precursor for AEA and 2-AG, and its increased dietary intake has been shown to directly elevate levels of these endocannabinoids. This elevation can lead to enhanced CB1 receptor activation, which promotes adipogenesis, increasing food intake, and reducing energy expenditure, thereby starting a recurring feedback loop which drives obesity.

Activation of the endocannabinoid system, a key pathway in alcohol and drug addiction that by itself induces drug-seeking responses by increasing dopamine levels and interacting with the corticostriatal part of the reward system.

This system activation results in significant weight gain even under low-fat diet conditions or in the presence of a diet that would not typically promote weight gain.

These findings are corroborated by human studies that indicate a similar trend, where elevated dietary linoleic acid correlates with increased adiposity and higher risk of metabolic disorders.

CB1 Activation In The Liver

Moreover, the interaction between linoleic acid-derived endocannabinoids and the CB1 receptor in the liver further exacerbates metabolic dysregulation.

Activation of hepatic CB1 receptors by endocannabinoids has been shown to induce steatosis, dyslipidemia, and insulin resistance, all of which are hallmarks of metabolic syndrome associated with obesity.

There is compelling evidence that the hepatic CB1 receptor is essential for the development of diet-induced steatosis and insulin resistance, highlighting the role of linoleic acid in promoting these adverse metabolic outcomes through endocannabinoid signaling.

Food intake

Additionally, the endocannabinoid system’s role in modulating food intake and energy balance is influenced by the types of fatty acids consumed in the diet with linoleic acid particularly enhancing endocannabinoid levels that drive hyperphagia (rabid hunger), further linking this fatty acid to obesity.

This mechanism underscores the complex interplay between dietary components and the endocannabinoid system in regulating body weight and composition.

Generational Degradation

The obesity problem of today doesn’t look like the obesity problem of the 2000’s and for that matter of the 1980’s. Mice fed a diet high in linoleic acid and then randomly mated over four generations whilst maintaining the diet showed ever increasing fat mass due to combined hyperplasia and hypertrophy with no change in food intake across each generation.

So we observe, high linoleic acid diets compound the obesity problem over generations, an adaptation not seen in any competing theories of obesity.

The broader implications of these findings suggest that reducing dietary linoleic acid intake is a viable strategy for preventing and managing obesity.

By lowering the precursor availability for endocannabinoid synthesis, it may be possible to attenuate the overactivation of CB1 receptors and their downstream effects on metabolism and energy balance.

This approach aligns with emerging nutritional recommendations that advocate for a reduction in omega-6 fatty acid consumption, particularly in the context of an increasingly obesogenic environment.

In conclusion, linoleic acid’s role in obesity is multifaceted, involving its conversion into bioactive endocannabinoids that modulate key physiological processes linked to energy balance and metabolism.

The evidence from both animal models and human studies underscores the importance of dietary fatty acid composition in influencing endocannabinoid system activity and, consequently, obesity risk.

Why Eating Linoleic Acid (Seed Oils) Is The Primary Driver in Obesity [Video]

But I Never Ate Seed Oils, Why Am I Obese?

The reality is, even if you haven’t directly poured canola oil into a glass and drank it, you’ve probably consumed seed oils without realizing it. Most foods that come in a box or package from the grocery store—things like chips, cookies, or frozen meals—contain seed oils.

For the last 30 years, these oils, particularly ones high in linoleic acid (the main fat found in seed oils), have become a huge part of the modern diet, way beyond what our bodies are used to from an evolutionary standpoint.

There’s another piece that sneaks under the radar: the way we raise animals today, especially animals like chickens, pigs, and turkeys. The food we feed them is loaded with these fats, and when you eat things like pork, chicken or turkey, you’re getting a big dose of linoleic acid.

Some experts even compare modern pork fat (lard) to seed oils like soybean oil because it’s so saturated with similar types of fats. So, even if you think you’ve avoided seed oils, odds are they’ve been in your diet indirectly.

But here’s where things get a little more complex—and it’s important to recognize that not everything comes down to just seed oils. Linoleic acid is likely one of the key contributors to obesity in the U.S. today, but it’s not the only factor. Even if you’ve avoided seed oils most of your life, other things could still be influencing your weight.

For some people, it could be emotional trauma, chronic stress, or environmental toxins like heavy metals or mold exposure. Genetics, and even epigenetics (how your genes are influenced by your environment), also play a role. It’s not a one-size-fits-all situation, and it’s important to approach this with empathy and an open mind.

At Uncivilized, we’ll keep digging into these topics—challenging conventional wisdom and exploring all the hidden factors that can affect health. Whether it’s seed oils, emotional health, or environmental triggers, we’re here to help you understand the full picture.

Further research of Linoleic Acid in Obesity

Explore further studies on the role of linoleic acid and its metabolites on Obesity:

Obesity & Linoleic Acid on (1417 studies – Pubmed)

Obesity & Lipid Peroxidation (1521 studies – Pubmed)

Obesity & Omega 6 (1240 studies – Pubmed)

Obesity & Oxidative Stress (11823 studies – Pubmed)

Sources

Dietary linoleic acid elevates the endocannabinoids 2-AG and anandamide and promotes weight gain in mice fed a low-fat diet.

https://doi.org/10.1007/s11745-013-3842-y

Fatty Acid Modulation of the Endocannabinoid System and the Effect on Food Intake and Metabolism.

https://doi.org/10.1155/2013/361895

Role of Cannabinoids in Obesity.

https://doi.org/10.3390/ijms19092690

Hepatic CB1 receptor is required for development of diet-induced steatosis, dyslipidemia, and insulin and leptin resistance in mice.

https://doi.org/10.1172/JCI34827

A Western-like fat diet is sufficient to induce a gradual enhancement in fat mass over generations

https://pubmed.ncbi.nlm.nih.gov/20410018/

Cannabinoids and the endocannabinoid system in reward processing and addiction: from mechanisms to interventions

https://pubmed.ncbi.nlm.nih.gov/33162767/​​

Physiological protection against weight gain: evidence from overfeeding studies and future directions

https://royalsocietypublishing.org/doi/10.1098/rstb.2022.0229