Success of Big Drug is Failure of Public Health

Pfizer has owns the rights to the drug Enbrel outside North America. Internal analysis at the company showed that there was a strong correlation to lower incidence of Alzheimer’s. It was an amazing 64% reduction. This is almost unheard of in Alzheimer’s research. At a company presentation, it was stated in no uncertain terms that, “Enbrel could potentially safely prevent, treat and slow progression of Alzheimer’s disease” (as quoted by Mark Terry).

Yet they didn’t follow up with more data analysis and clinical studies. Neither did they publicly release their findings. Pfizer can’t take all the blame, though. The company works with the Amgen in marketing Enbrel. This other drug company holds the patent and rights to market Enbrel in the United States and Canada. Both drug companies knew about the results and both remained silent. A company spokesman for Pfizer told the Washington Post that, “Science was the sole determining factor against moving forward.” I don’t doubt that is true for corporate science. But there sometimes is a vast difference between corporate science and non-profit science. This is indicated by another explanation that came out of Pfizer.

The WaPo reported that, the company “decided during its three years of internal reviews that Enbrel did not show promise for Alzheimer’s prevention because the drug does not directly reach brain tissue.” That is odd because, based on much research, we know there is more involved in Alzheimer’s than just the brain. The only proven clinical trial that has reversed Alheimer’s symptoms used a protocol that included many methods, including the ketogenic diet (see the clinical study and writings of Dr. Dale Bredesen).

The US FDA approved use of Enbrel is for the treatment of autoimmune diseases: rheumatoid arthritis, juvenile idiopathic arthritis and psoriatic arthritis, plaque psoriasis and ankylosing spondylitis. The effect it would have on Alzheimer’s is as an anti-inflammatory. This could be achieved in many ways, such as broadly reducing an overactive immunological response in the body, not only in the brain. The neurocognitive effect might be indirect and secondary to the process without the drug needing to cross the blood-brain barrier. It isn’t necessarily significant by which path, neurological or not, that it accomplishes this feat of inflammatory reduction. As reported in the WaPo:

Yet Alzheimer’s researchers believe inflammation outside the brain — called peripheral inflammation — influences inflammation within the brain.

“There is a lot of evidence suggesting that peripheral or systemic inflammation may be a driver of Alzheimer’s disease,’’ said Walker, the Johns Hopkins researcher. It is a fair hypothesis that fighting inflammation outside the brain with Enbrel will have a similar effect inside the brain, he said.

“I don’t believe Enbrel would need to cross the blood brain barrier to modulate the inflammatory/immune response within the brain,’’ Walker said.

“There is increasing evidence that peripheral inflammation can influence brain function,’’ said rheumatologist Christopher Edwards, of the University of Southampton in Britain.

I refuse to believe that the researchers at Enbrel didn’t know this basic scientific understanding and didn’t explain it to those making the decisions. Maybe that is why the scientists employed by Pfizer, in opposition to the management, were pushing for more research to be done.

Basically, it was a business decision and so it was irrelevant even if it was guaranteed to cure Alzheimer’s. In capitalism, there is no financial incentive in humanitarianism, at least not when its costly. As Enbrel was already patented for another medical use and its patent life was coming to an end, getting it patented for an entirely different health condition would have been difficult because of patent laws. It would have been a high-risk business investment with low probability of success and profit.

Since it wasn’t profitable for the company to pursue further research, it also wouldn’t have been profitable for the company to release the info so that others might pursue further research or else simply gain better understanding about the possibilities of different avenues of research. Promoting scientific debate and scientific knowledge is not part of capitalism (ditto for public health), other than as an unintentional side effect. No company will freely choose to disclose any information beyond what is necessary or else when deemed unrelated to any financial gain… that is unless required by law, in which case it wouldn’t be freely chosen.

If you want to hear defenses of the actions or rather inaction of Pfizer, some pieces have been written taking the other side of the debate: A Missed Alzheimer’s Opportunity? Not So Much by Derek Lowe, and 5 Reasons Pfizer Sat on a Potential New Alzheimer’s Drug by Cory Renauer. Pfizer also went to its own defense on social media: Pfizer takes to Twitter to refute ‘Washington Post’ story by Alison Kanski. I find the excuses unconvincing. It comes across more as apologia for capitalist realism.

Still, to be fair, there has been immense failure in Alzheimer’s research. A new drug treatment hasn’t been approved by the FDA in the past decade. But that is part of the problem with the corporate model of big drug. The only promising research in recent years is from methods other than pharmaceuticals. As far as capitalism goes, it doesn’t matter if Alzheimer’s can be treated and reversed with a multifactorial approach, by a combination of diet, nutrition, supplementation, exercise, detoxification, etc. There is no profit in this, since no company can patent it and so monopolize the market for decades. In that sense, it is pointless in blaming a corporation for acting like a corporation. This is the inevitable result of capitalism.

Following the obvious financial incentive, Pfizer has stopped Alzheimer’s research. This is problematic for public health, of course. Big biz, however, doesn’t give a flying fuck about public health. If we are seeking public health, then governments will have to massively invest in public funding of research and development as the United States did in the past. Instead, public funding has been drastically cut. This is expected in corporatocratic government where corporate interests determine public policy. It’s the nature of the beast. If we think it is morally wrong to let millions of people to suffer and die when there is no profit in helping them, then we will be forced by our collective conscience to demolish our present economic and political system and then replace it with something better.

But it goes beyond even this. The causes of inflammation are diverse. With industrialized capitalism, we are drowning in physiological and social stressors, from toxins to inequality, that constantly antagonize the body while disallowing the natural processes of healing. We need an entirely different model and paradigm to confront what is causing the worsening of health across the board: metabolic syndrome (obesity, diabetes, & heart disease), autoimmune disorders (Alzheimer’s, multiple sclerosis, etc), mood disorders (depression, anxiety, etc), and personality disorders (BPD, NPD, etc); psychosis, ADHD, autism spectrum disorders, drug addiction, and on and on. A common feature found in numerous health conditions is inflammation.

When the entire social order, from economic system to food system, is inflammatory and generally harmful to public health, what is the treatment? And even if we could find effective treatments, why would we settle for that rather than seeking cures and prevention? Why are we obsessed with symptoms, instead of going directly to the root cause of so many diseases?

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Pfizer had clues its blockbuster drug could prevent Alzheimer’s. Why didn’t it tell the world?
by Christopher Rowland

A team of researchers inside Pfizer made a startling find in 2015: The company’s blockbuster rheumatoid arthritis therapy Enbrel, a powerful anti-inflammatory drug, appeared to reduce the risk of Alzheimer’s disease by 64 percent.

The results were from an analysis of hundreds of thousands of insurance claims. Verifying that the drug would actually have that effect in people would require a costly clinical trial — and after several years of internal discussion, Pfizer opted against further investigation and chose not to make the data public, the company confirmed.

Researchers in the company’s division of inflammation and immunology urged Pfizer to conduct a clinical trial on thousands of patients, which they estimated would cost $80 million, to see if the signal contained in the data was real, according to an internal company document obtained by The Washington Post.

“Enbrel could potentially safely prevent, treat and slow progression of Alzheimer’s disease,’’ said the document, a PowerPoint slide show that was prepared for review by an internal Pfizer committee in February 2018.

The company told The Post that it decided during its three years of internal reviews that Enbrel did not show promise for Alzheimer’s prevention because the drug does not directly reach brain tissue. It deemed the likelihood of a successful clinical trial to be low. A synopsis of its statistical findings prepared for outside publication, it says, did not meet its “rigorous scientific standards.’’

Science was the sole determining factor against moving forward, company spokesman Ed Harnaga said.

Pfizer Did Not Pursue Possible Evidence of Enbrel Helping with Alzheimer’s Due to Low Chance of Clinical Success
by Mark Terry

Recently released documents indicate that Pfizer spent three years reviewing whether the science supported running a trial on Enbrel in Alzheimer’s. A PowerPoint slide from a February 2018 presentation stated, “Enbrel could potentially safely prevent, treat and slow progression of Alzheimer’s disease.”

But the company told The Washington Post that during those three years, they felt that the drug didn’t show promise for Alzheimer’s because it doesn’t directly reach brain tissue. So, they believed that the clinical trial’s chances of success would be low. Pfizer spokesman Ed Harnaga told The Post that the only reason the company didn’t go forward was the science.

That may or may not be reasonable, but the company’s decision not to release or publish the data is taking more criticism, with many researchers arguing they should have made that data available to researchers.

“Of course they should. Why not?” Rudolph E. Tanzi, a top Alzheimer’s researcher with Harvard Medical School and Massachusetts General Hospital.

In fact, in an interview with Tanzi earlier this year, he noted that more and more research is focused on the role of inflammation in Alzheimer’s, particularly as the amyloid-beta theory comes under fire. In Tanzi’s opinion, and there’s quite a bit of scientific research supporting it, amyloid and tangles trigger Alzheimer’s, but they’re not enough to cause dementia. But the amyloid and tangle-driven neuronal cell death eventually hits a point where the brain’s innate immune system reacts with significant levels of neuroinflammation. Tanzi told BioSpace, “Then, exponentially more cell death occurs, which leads to symptoms of dementia and Alzheimer’s disease.”

So it seems possible that a powerful anti-inflammatory like Enbrel could have a dampening effect on the entire immune system, which might decrease Alzheimer’s risk. […]

It also seems contradictory that when so many biopharma companies are investing in artificial intelligence and data mining of real-world evidence (RWE) such as the Pfizer scientists utilized in 2015, that they would then ignore what they found.

Pfizer recognizes that it hid a drug that prevents Alzheimer’s
from The Mazatlan Post

This American media also explains in its exclusive that the role of brain inflammation in Alzheimer’s disease has been attracting the attention of academics after the failure of multiple experimental drugs that pointed to the accumulation of plaques in brain tissue.

“People who have chronic inflammation have a higher risk of developing Alzheimer’s”

Thus, they recall that in 2016 researchers from the universities of Dartmouth and Harvard published an insurance claims data study , similar to the internal findings of Pfizer (for those who refused to continue investigating the possible new use of their drug) that showed a potential benefit of Enbrel.

Enbrel “shows promise as a potential treatment” For Alzheimer’s, he pointed out.” In this study, it is said that Alzheimer’s is significantly more prevalent in patients with rheumatoid arthritis, a fact that was already known: people who have chronic inflammation have a higher risk of developing Alzheimer’s. Also, those who were taking the Pfizer drug had a decreased risk, “explains the SEN member, who points out that there is evidence in basic research.

However, Pascual Sanchez says that […] “Of course it is a piece of interesting information [published by the Washington Post], and of course it is a line that, taking into account that others have not worked, such as amyloid, we are very interested in it.” There is strong genetic evidence and targets are being developed based on modulation of inflammation. ”

“We urgently need the pharmaceutical laboratories to bet on Alzheimer’s disease. Unfortunately, Pfizer has strategically abandoned the line of Neurology, and has probably been one of the reasons why not bet on it, “says Sanchez.

The expert says that Alzheimer’s disease is very complex and” from pharmaceutically no Much progress has been made. The pharmaceutical companies that have bet for now have not achieved benefits because they have not taken new drugs, but increasingly we know more and we do better clinical trials. I think there are more options for us to find something that works. And the more you invest, and the more people think about this, the more likely we are to achieve it, “he says.

“We need to do more trials and probably need more complex approaches to this disease, we are realizing that we will need several treatments or different simultaneous approaches to treat the disease, there are many factors that are involved, such as amyloid, TAU protein, inflammation or even p43, probably if we focus only on one factor we will not succeed, we must have a more global vision of the problem and also of the solutions”, concludes Pascual Sánchez.

Pfizer, pocketing a big tax cut from Trump, will end investment in Alzheimer’s and Parkinson’s research
by Michael Hiltzik

No one would say that drug companies should engage in research as a philanthropic exercise, but within the context of the U.S. pharmaceutical industry, Pfizer looks risk-averse. The second-biggest U.S. drug company by sales (after Johnson & Johnson), Pfizer in recent years seems to have devoted more effort to financial engineering than biomedical engineering. In 2015, for instance, it announced a $160-billion merger with Allergan, the maker of Botox. The deal was a so-called inversion, aimed transparently at cutting Pfizer’s tax bill in part by eliminating U.S. tax on $147 billion in profits it had stashed overseas.

Although the company denied that the deal was “simply… a tax transaction,” the truth emerged in 2016 when the deal was canceled; the only thing that had changed was that the U.S. Treasury had implemented new rules that all but eliminated the tax savings. So, bye-bye, Allergan.

Pfizer is expected to be among the prime beneficiaries of the corporate tax cut. The measure allows companies to pay a tax rate as low as 8% on foreign earnings they bring home, a big discount from the 21% top rate the law assesses on domestic earnings, itself a big cut from the previous rate of 35%. By some estimates, that could be worth more than $5 billion to Pfizer alone, not counting any gains from the lower tax rate.

As it happens, Pfizer signaled how it would apply the tax savings even before the final passage of the tax bill: The company announced a $10-billion share buyback on Dec. 18, four days before President Trump signed the tax cut into law. That buyback was on top of $6.4 billion left to be spent from a previous buyback plan, and was accompanied by a 6% increase in the company’s stock dividend, which will be worth roughly another half-billion dollars a year.

For comparison’s sake, Pfizer’s entire research and development budget averaged about $8 billion a year from 2014 through 2016.

Pfizer’s diversion of its tax break to shareholders parallels its behavior the last time American companies received a tax holiday on repatriated foreign earnings. That was in 2004, after corporations promised to apply their tax savings to hiring more workers and investing in their business. Instead, they laid off workers, bought back their shares, and pumped up their CEO compensation.

Pfizer brought home more than any other company in that amnesty, $35.5 billion, according to a 2007 investigation by Sen. Carl Levin, D-Mich. From 2004 through 2007, Levin reported, Pfizer bought back more than $27 billion in stock and reduced employment by 11,748 workers.

This time around, the company is again gifting its shareholders and laying off workers. Abandoning a challenging research field is a new wrinkle, however.

What’s most discouraging to patient advocates is the dearth of alternatives to big pharmaceutical companies in brain research. Pfizer’s withdrawal, especially if it prompts other big pharma companies to flee the field, places more of the burden on small biotech firms, academia, foundations and government. The news “reinforces the urgent need for additional federal investment in Alzheimer’s research,” a spokesman for the Alzheimer’s Foundation of America told me. But the Trump administration has placed funding for government research projects in almost all scientific fields on the chopping block.

Some experts recognize that the big drug companies may have been less than sturdy partners all along. “Many groups have been hoping for quick wins in the [central nervous system] space and we haven’t succeeded,” Beck of the Parkinson’s Foundation says, “so there’s some frustration from the viewpoint of management that we’re not getting the progress we need.”

He says his organization and others will still focus on the most promising pathway to a cure: Trying to understand the mechanisms of these diseases, which are still very murky. Only once those riddles are solved can drug research truly move ahead.

But as long as purely economic considerations drive drug R&D, the prospects for progress are dim. The Republicans who drafted the corporate tax cut promised that it would lead to more business investment and therefore economic growth. But as Pfizer demonstrates, all the incentives run in the opposite direction: More investment in shareholder welfare, less economic growth, and less attention to what corporations are supposed to exist for — improving people’s lives.

Profits before people: capitalists abandon Alzheimer’s and Parkinson’s research
by Joe Attard

Pfizer’s announcement is an especially striking testament to the horrors of capitalism when seen in context with the damage caused by Alzheimer’s and Parkinson’s. For example, the global cost of Alzheimer’s and dementia (in terms of medical care, social care and hospices) is estimated at $605 billion: equivalent to 1 percent of the entire world’s gross domestic product. Meanwhile, the financial impact incurred for a UK citizen living with Parkinson’s disease (which affects mobility, and eventually communication) are £16,000 per year on average – factoring in assistance with cleaning, loss of income and benefits and so on. For the poorest Parkinson’s’ sufferers, professional help might be unaffordable, placing the duty of care on family members.

Pfizer pulling out of Alzheimer’s and Parkinson’s research will shunt more of the burden of seeking treatments for these diseases on the public sector – via universities, for example. That is, as is becoming the norm, they leave the bill for research to be paid for by taxpayers, only to take over the patents for small change at a later stage. […]

The main driving force for Pfizer is cold, hard profit. Its R&D chief, Mikael Dolsten, recently told a J.P. Morgan healthcare conference that the company bases its R&D strategy on drugs with “multi-billion-dollar blockbuster potential.” These drug giants focus their attention on whatever nets the biggest windfalls with the least amount of effort, which can lead to an emphasis on manufacturing financial loopholes rather than medicines. In 2015, Pfizer acquired Allergan (the company that makes Botox) in a $160-billion merger: a move that eliminated U.S. tax on $147 billion in profits it had stashed overseas. In Britain, despite making sales of between £1.3bn and £1.8bn annually between 2001 and 2014, Pfizer paid almost no tax over the period because it announced major operating losses each year, except for a tiny profit of £9m in 2013. The company is also expected to benefit substantially from Donald Trump’s new corporate tax cut, to the tune of $5bn: 10 times more than the US government’s 2017 pledge to Alzheimer’s research, and more than half of Pfizer’s entire research and development budget from 2014 through 2016. Donald Trump has generously rewarded Pfizer’s shareholders, who have responded by slashing early development research on neurological diseases, firing hundreds of employees and continuing to inflate the cost of its products.

This should all come as no surprise. The whole medical industry has become thoroughly parasitical, making billions from ripping off state healthcare services, withholding essential medicines from Third World countries and lobbying governments to deregulate the healthcare market. Pfizer was itself hit with a record fine in 2016 after it charged the NHS £50m for an anti-epilepsy drug: up from £2m in 2013. For years Pfizer withheld fluconzale (a powerful anti-fungal agent that can be used to treat AIDS-related diseases like oral thrush and cryptococcal meningitis) from the developing world, while continuing to sell it to wealthy American and European patients. Only after provoking international outrage did it make the drug available to NGOs operating in developing countries with a greater than 1 percent prevalence of HIV/AIDS in 2001. The firm has also never been shy about using its financial clout to get its way in the political sphere, spending $25 million in 2010 alone on lobbying for healthcare deregulation in the USA. Big business and the state are connected to each other by a thousand threads. Despite Donald Trump’s promises during the primaries that he would reign in Big Pharma, his appointment of former pharmaceutical executive Alex Azar to replace Tom Price as Health and Human Services Secretary suggests otherwise.

In stark contrast to claims that free market competition fosters innovation, the private pharmaceutical industry reveals the stagnation, irrationality and base cruelty of capitalism in its state of senile decay. From Martin Shkreli’s jacking up the cost of Daraprim (a drug used in the treatment of AIDS-related conditions) from US$13.50 to US$750 per pill; to drug giants profiteering off AIDS epidemics in Africa and Asia; to Big Pharma taking public money (in the form of tendered contracts) from the NHS and stashing it in tax havens, the logic of capitalism ensures that healthy profits always take precedence over public health. Moreover, Pfizer’s actions demonstrate the sheer barbarism of allowing vast reserves of money, expertise and talent to be wasted or misdirected by private medical firms. Permitting research priorities to be dictated by market forces has resulted in pharmaceutical giants directing more attention towards lifestyle drugs targeted at the wealthy – designed to treat such tragic conditions as obesity, baldness, wrinkles and impotence. There is a multi-billion-dollar market for such products. Meanwhile, the difficult, expensive work of producing treatments for illnesses like Alzheimer’s and Parkinson’s disease is sacrificed to the bottom line.

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Essentialism On the Decline

Before getting to the topic of essentialism, let me take an indirect approach. In reading about paleolithic diets and traditional foods, a recurring theme is inflammation, specifically as it relates to the health of the gut-brain network and immune system.

The paradigm change this signifies is that seemingly separate diseases with different diagnostic labels often have underlying commonalities. They share overlapping sets of causal and contributing factors, biological processes and symptoms. This is why simple dietary changes can have a profound effect on numerous health conditions. For some, the diseased state expresses as mood disorders and for others as autoimmune disorders and for still others something entirely else, but there are immense commonalities between them all. The differences have more to do with how dysbiosis and dysfunction happens to develop, where it takes hold in the body, and so what symptoms are experienced.

From a paleo diet perspective in treating both patients and her own multiple sclerosis, Terry Wahls gets at this point in a straightforward manner (p. 47): “In a very real sense, we all have the same disease because all disease begins with broken, incorrect biochemistry and disordered communication within and between our cells. […] Inside, the distinction between these autoimmune diseases is, frankly, fairly arbitrary”. In How Emotions Are Made, Lisa Feldman Barrett wrote (Kindle Locations 3834-3850):

“Inflammation has been a game-changer for our understanding of mental illness. For many years, scientists and clinicians held a classical view of mental illnesses like chronic stress, chronic pain, anxiety, and depression. Each ailment was believed to have a biological fingerprint that distinguished it from all others. Researchers would ask essentialist questions that assume each disorder is distinct: “How does depression impact your body? How does emotion influence pain? Why do anxiety and depression frequently co-occur?” 9

“More recently, the dividing lines between these illnesses have been evaporating. People who are diagnosed with the same-named disorder may have greatly diverse symptoms— variation is the norm. At the same time, different disorders overlap: they share symptoms, they cause atrophy in the same brain regions, their sufferers exhibit low emotional granularity, and some of the same medications are prescribed as effective.

“As a result of these findings, researchers are moving away from a classical view of different illnesses with distinct essences. They instead focus on a set of common ingredients that leave people vulnerable to these various disorders, such as genetic factors, insomnia, and damage to the interoceptive network or key hubs in the brain (chapter 6). If these areas become damaged, the brain is in big trouble: depression, panic disorder, schizophrenia, autism, dyslexia, chronic pain, dementia, Parkinson’s disease, and attention deficit hyperactivity disorder are all associated with hub damage. 10

“My view is that some major illnesses considered distinct and “mental” are all rooted in a chronically unbalanced body budget and unbridled inflammation. We categorize and name them as different disorders, based on context, much like we categorize and name the same bodily changes as different emotions. If I’m correct, then questions like, “Why do anxiety and depression frequently co-occur?” are no longer mysteries because, like emotions, these illnesses do not have firm boundaries in nature.”

What jumped out at me was the conventional view of disease as essentialist, and hence the related essentialism in biology and psychology.

[…]

Researchers have found that there are prospective causes to be studied. Consider proprionate, a substance discussed by Alanna Collen (10% Human, p. 83): “although propionate was an important compound in the body, it was also used as a preservative in bread products – the very foods many autistic children crave. To top it all off, clostridia species are known to produce propionate. In itself, propionate is not ‘bad’, but MacFabe began to wonder whether autistic children were getting an overdose.” This might explain why antibiotics helped many with autism, as it would have been knocking off the clostridia population that was boosting propionate. To emphasize this point, when rodents were injected with propionate, they exhibited the precise behaviors of autism and they too showed inflammation in the brain. The fact that autistics often have brain inflammation, an unhealthy condition, is strong evidence that autism shouldn’t be taken as mere neurodiversity (and, among autistics, the commonality of inflammation-related gut issues emphasizes this point).

There is no doubt that genetic determinism, like the belief in an eternal soul, can be comforting. We identify with our genes, as we inherit them and are born with them. But to speak of inflammation or propionate or whatever makes it seem like we are victims of externalities. And it means we aren’t isolated individuals to be blamed or to take credit for who we are. To return to Collen (pp. 88-89):

“In health, we like to think we are the products of our genes and experiences. Most of us credit our virtues to the hurdles we have jumped, the pits we have climbed out of, and the triumphs we have fought for. We see our underlying personalities as fixed entities – ‘I am just not a risk-taker’, or ‘I like things to be organised’ – as if these are a result of something intrinsic to us. Our achievements are down to determination, and our relationships reflect the strength of our characters. Or so we like to think.

“But what does it mean for free will and accomplishment, if we are not our own masters? What does it mean for human nature, and for our sense of self? The idea that Toxoplasma, or any other microbe inhabiting your body, might contribute to your feelings, decisions and actions, is quite bewildering. But if that’s not mind-bending enough for you, consider this: microbes are transmissible. Just as a cold virus or a bacterial throat infection can be passed from one person to another, so can the microbiota. The idea that the make-up of your microbial community might be influenced by the people you meet and the places you go lends new meaning to the idea of cultural mind-expansion. At its simplest, sharing food and toilets with other people could provide opportunity for microbial exchange, for better or worse. Whether it might be possible to pick up microbes that encourage entrepreneurship at a business school, or a thrill-seeking love of motorbiking at a race track, is anyone’s guess for now, but the idea of personality traits being passed from person to person truly is mind-expanding.”

This goes beyond the personal level, which lends a greater threat to the proposal. Our respective societies, communities, etc might be heavily influenced by environmental factors that we can’t see. A ton of research shows the tremendous impact of parasites, heavy metal toxins, food additives, farm chemicals, hormones, hormone mimics, hormone disruptors, etc. Entire regions might be shaped by even a single species of parasite, such as how higher rates of toxoplasmosis gondii in New England is directly correlated to higher rates of neuroticism (see What do we inherit? And from whom? & Uncomfortable Questions About Ideology).

Health From Generation To Generation

To emphasize this point, the testing of newborn babies in the United States shows that they’ve already accumulated on average more than 200 synthetic chemicals from within the womb; and then imagine all the further chemicals they get from the breast milk of their unhealthy mothers along with all kinds of crap in formulas and in their environments (e.g., carcinogenic fire retardants that they breathe 24/7). Lead toxicity has decreased since my own childhood and that is a good thing, but thousands of new toxins and other chemicals have replaced it. On top of that, the hormones, hormone mimics, and hormone disruptors add to dysbiosis and disease — some suggesting this is a cause of puberty’s greater variance than in past generations, either coming earlier or later depending on gender and other factors (maybe partly explaining the reversal and divergence of educational attainment for girls and boys). Added to this mix, this is the first generation of human guinea pigs to be heavily medicated from childhood, much of it medications that have been shown to permanently alter neurocognitive development.

A major factor in many modern diseases is inflammation. This has many causes from leaky gut to toxicity, the former related to diet and often contributing to the latter (in how the leaky gut allows molecules to more easily cross the gut lining and get into the bloodstream where they can freely travel throughout the body — causing autoimmune disorders, allergies, asthma, rheumatoid arthritis, depression, etc). But obesity is another main cause of inflammation. And one might note that, when the body is overloaded and not functioning optimally, excess toxins are stored in fat cells — which makes losing weight even more difficult as toxins are released back into the body, and if not flushed out causing one to feel sick and tired.

It’s not simply bad lifestyle choices. We are living in unnatural and often outright toxic conditions. Many of the symptoms that we categorize as diseases are the bodies attempt to make the best of a bad situation. All of this adds up to a dysfunctional level across society. Our healthcare system is already too expensive for most people to afford. And the largest part of public funding for healthcare is going to diabetes alone. But the saddest part is the severe decrease in quality of life, as the rate of mood and personality disorders skyrockets. It’s not just diet. For whatever reason (toxins? stress?), with greater urbanization has come greater levels of schizophrenia and psychosis. And autism, a rare condition in the past, has become highly prevalent (by the way, one of the proven effective treatments for autism is a paleo/keto diet; also effective for autoimmune conditions among much else).

It’s getting worse and worse, generation after generation. Imagine what this means in terms of epigenetics and transgenerational trauma, as nutritional deficits and microbiotic decimation accumulates, exacerbated by a society driven mad through inequality and instability, stress and anxiety. If not for nutrients added to our nutrient poor food and supplements added to our unhealthy diet, we’d already be dying out as a society and our civilization would’ve collapsed along with it (maybe similar to how some conjecture the Roman Empire weakened as lead toxicity increased in the population). Under these conditions, that children are our future may not be an affirmation of hope. Nor may these children be filled with gratitude once they’ve reached adulthood and come to realize what we did to them and the world we left them. On the other hand, we aren’t forced to embrace fatalism and cynicism. We already know what to do to turn around all of these problems. And we don’t lack the money or other resources to do what needs to be done. All that we are waiting for is public demand and political will, although that might first require our society reaching a point of existential crisis… we are getting close.

The stumbling block is that there is no profit in the ‘healthcare’ industry for advocating, promoting, incentivizing, and ensuring healthy diet and healthy conditions for a healthy population. Quite the opposite. If disease profiteering was made illegal, there would be trillions of dollars of lost profit every year. Disease is the reality of capitalist realism, a diseased economic system and social order. This collective state of sickliness has become the norm and vested interests will go to great lengths to defend the status quo. But for most who benefit from the dysfunctional and destructive system, they never have to give it much thought. When my mother brought my nephew to the doctor, she pointed out how he is constantly sick and constantly eating a poor diet. The doctor’s response was that this was ‘normal’ for kids (these days), which might be true but the doctor should be shocked and shamed by his own admission. As apathy takes hold and we lose a sense of hope, low standards fall ever lower.

Fasting, Calorie Restriction, and Ketosis

Fasting, for example, increases the level of neurotransmitters such as serotonin, dopamine, and norepinephrine while temporarily reducing the brains release and use of them; plus, serotonin and its precursor tryptophan are made more available to the brain. So, it allows your reserves of neurotransmitters to rebuild to higher levels. That is partly why a ketogenic diet, along with the brains efficient use of ketones, shows improvements in behavior, learning, memory, acuity, focus, vigilance, and mood (such as sense of well-being and sometimes euphoria); with specific benefits, to take a couple of examples, in cerebral blood flow and prefrontal-cortex-related cognitive functions (mental flexibility and set shifting); while also promoting stress resistance, inflammation reduction, weight loss, and metabolism, and while decreasing free radical damage, blood pressure, heart rate, and glucose levels. Many of these are similar benefits as seen with strenuous exercise.

We know so much about this because the ketogenic diet is the only diet that has been specifically and primarily studied in terms of neurological diseases, going back to early 20th century research on epileptic seizures and autism, was shown effective for other conditions later in the century (e.g., V. A. Angelillo et al, Effects of low and high carbohydrate feedings in ambulatory patients with chronic obstructive pulmonary disease and chronic hypercapnia), and more recently with positive results seen in numerous other conditions (Dr. Terry Wahl’s work on multiple sclerosis, Dr. Dale Bredesen’s work on Alzheimer’s, etc). By the way, the direction of causality can also go the other way around, from brain to gut: “Studies also suggest that overwhelming systemic stress and inflammation—such as that induced via severe burn injury—can also produce characteristic acute changes in the gut microbiota within just one day of the sustained insult [15].” (Rasnik K. Singh et al, Influence of diet on the gut microbiome and implications for human health). And see:

“Various afferent or efferent pathways are involved in the MGB axis. Antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, essential metabolites, all convey information about the intestinal state to the CNS. Conversely, the HPA axis, the CNS regulatory areas of satiety and neuropeptides released from sensory nerve fibers affect the gut microbiota composition directly or through nutrient availability. Such interactions appear to influence the pathogenesis of a number of disorders in which inflammation is implicated such as mood disorder, autism-spectrum disorders (ASDs), attention-deficit hypersensitivity disorder (ADHD), multiple sclerosis (MS) and obesity.” (Anastasia I. Petra et al, Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation) […]

For example, a ketogenic diet modulates the levels of the microbes Akkermansia muciniphila, Lactobacillus, and Desulfovibrio (Lucille M. Yanckello, Diet Alters Gut Microbiome and Improves Brain Functions). It is the microbes that mediate the influence on both epileptic seizures and autism, such that Akkermansia is decreased in the former and increased in the latter, that is to say the ketogenic diet helps the gut regain balance no matter which direction the imabalance is. In the case of epileptic seizures, Akkermansia spurs the growth of Parabacteroides which alters neurotransmission by elevating the GABA/glutamate ratio (there is glutamate again): “the hippocampus of the microbe-protected mice had increased levels of the neurotransmitter GABA, which silences neurons, relative to glutamate, which activates them” (Carolyn Beans, Mouse microbiome findings offer insights into why a high-fat, low-carb diet helps epileptic children), but no such effect was found in germ-free mice, that is to say with no microbiome (similar results were found in human studies: Y. Zhang, Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet). Besides reducing seizures, “GABA is a neurotransmitter that calms the body. Higher GABA to glutamate ratios has been shown to alleviate depression, reduce anxiety levels, lessen insomnia, reduce the severity of PMS symptoms, increase growth hormone, improve focus, and reduce systemic inflammation” (MTHFR Support, Can Eating A Ketogenic Diet Change Our Microbiome?). To throw out the other interesting mechanism, consider Desulfovibrio. Ketosis reduces its numbers and that is a good thing since it causes leakiness of the gut barrier, and what causes leakiness in one part of the body can cause it elsewhere as well such as the brain barrier. Autoimmune responses and inflammation can follow. This is why ketosis has been found beneficial for preventing and treating neurodegenerative conditions like Alzheimer’s (plus, ketones are a useful alternative fuel for Alzheimer’s since their brain cells begin starving to death for loss of the capacity to use glucose as a fuel).

All of this involves the factors that increase and reduce inflammation: “KD also increased the relative abundance of putatively beneficial gut microbiota (Akkermansia muciniphila and Lactobacillus), and reduced that of putatively pro-inflammatory taxa (Desulfovibrio and Turicibacter).” (David Ma et al, Ketogenic diet enhances neurovascular function with altered gut microbiome in young healthy mice). Besides the microbiome itself, this has immense impact on leakiness and autoimmune conditions, with this allowing inflammation to show up in numerous areas of the body, including the brain of course. Inflammation is found in conditions such as depression and schizophrenia. Even without knowing this mechanism, much earlier research has long established that ketosis reduces inflammation.

Trends in Depression and Suicide Rates

Stephen Ilardi made two very important points.

First, depression is a disease of civilization. He spoke of research done on a hunter-gatherer tribal people. What the researcher found was that depression was almost non-existent among them. They lived a hard life and often hard deaths, but they weren’t clinically depressed. Nor did they have many of the other diseases of civilization, all of which are related to inflammation in the body.

He points out that studies have shown that depression is related to inflammation in the brain, at least partly caused by an unhealthy ratio between Omega 6 fats and Omega 3 fats. Combined with the stresses and social isolation of modern society, clinical depression has become a massive problem.

Second, clinical depression is a growing problem. Each generation has higher rates of depression than the generation before. It correctly can be called an epidemic at this point and it increases as people age. The younger generations will as they age, if the pattern holds, have 50% or more experiencing clinical depression.

This gets at an issue I continually return to. Everything is getting worse for the young generation such as poverty, economic inequality, unemployment and homelessness. My generation is the first generation do worse than their parents in the 20th century. My generation as children had poverty rates not seen since the Great Depression and had the worst child suicide rates since such things were recorded. How bad does society have to get before even children become so desperate and hopeless that they kill themselves?

Most people in the older generations never personally experienced these kinds of conditions. Because of this, they have no tangible understanding, no sympathy. They can’t see how this is a systemic problem throughout society, a problem transcending individuals and even generations.

I’ve previously discussed this a bit in terms of capitalist realism (see here and here), but I’ve never gone into much detail about this before. The analysis behind the concept of capitalist realism is based on the collective inability to imagine alternatives and hence collective inability to perceive the problems of the present system. The individual is the product and the scapegoat of capitalist realism.