The Chemical Imbalance Myth and Antidepressant Harm

Article Source: Health And Fitness Journal

In the U.S., an estimated 17.3 million American adults (7.1% of the adult population), experienced at least one major depressive episode in 2017.1 The highest rates are reported among those aged between 18 and 25.2 However, not only is there evidence that depression is vastly overdiagnosed, but there’s also evidence showing it’s routinely mistreated.

With regard to overdiagnosis, one 2013 study3 found only 38.4% of participants with clinician-identified depression actually met the DSM-4 criteria for a major depressive episode, and only 14.3% of seniors 65 and older met the criteria.

As for treatment, the vast majority are prescribed antidepressant drugs, despite the fact there’s virtually no evidence to suggest they provide meaningful help, and plenty of evidence showing the harms are greater than patients are being told.

According to a 2017 study,4 1 in 6 Americans between the ages of 18 and 85 were on psychiatric drugs, most of them antidepressants, and 84.3% reported long-term use (three years or more). Out of 242 million U.S. adults, 12% were found to have filled one or more prescriptions for an antidepressant, specifically, in 2013.

According to data5 presented by a watchdog group, hundreds of thousands of toddlers are also being medicated with powerful psychiatric drugs, raising serious ethical questions, along with questions about the future mental and physical health of these children.

Recent studies are also shedding much needed light on the addictive nature of many antidepressants, and demonstrate that the benefits of these drugs have been overblown while their side effects — including suicidal ideation — and have been downplayed and ignored for decades, placing patients at unnecessary risk.

The Chemical Imbalance Myth

One researcher responsible for raising awareness about these important mental health issues is professor Peter C. Gøtzsche, a Danish physician-researcher and outspoken critic of the drug industry (as his book, “Deadly Medicines and Organized Crime: How Big Pharma Has Corrupted Healthcare,”6 suggests).

Gøtzsche helped found the Cochrane Collaboration in 1993 and later launched the Nordic Cochrane Centre. In 2018, he was expelled by the Cochrane governing board following the publication of a scathing critique of a Cochrane review of the HPV vaccine, in which he and his coauthors pointed out several methodological flaws and conflicts of interest.

Over the past several years, Gøtzsche has published a number of scientific papers on antidepressants and media articles and a book discussing the findings. In a June 28, 2019 article,7 Gøtzsche addresses “the harmful myth” about chemical imbalances — a debunked hypothesis that continues to drive the use of antidepressants to this day. He writes, in part:8

“Psychiatrists routinely tell their patients that they are ill because they have a chemical imbalance in the brain and they will receive a drug that fixes this …

Last summer, one of my researchers and I collected information about depression from 39 popular websites in 10 countries, and we found that 29 (74%) websites attributed depression to a chemical imbalance or claimed that antidepressants could fix or correct that imbalance …

It has never been possible to show that common mental disorders start with a chemical imbalance in the brain. The studies that have claimed this are all unreliable.9

A difference in dopamine levels, for example, between patients with schizophrenia and healthy people cannot tell us anything about what started the psychosis … [I]f a lion attacks us, we get terribly frightened and produce stress hormones, but this does not prove that it was the stress hormones that made us scared.

People with psychoses have often suffered traumatic experiences in the past, so we should see these traumas as contributing causal factors and not reduce suffering to some biochemical imbalance that, if it exists at all, is more likely to be the result of the psychosis rather than its cause.10

The myth about chemical imbalance is very harmful. It makes people believe there is something seriously wrong with them, and sometimes they are even told that it is hereditary.

The result of this is that patients continue to take harmful drugs, year after year, perhaps even for the entirety of their lives. They fear what would happen if they stopped, particularly when the psychiatrists have told them that their situation is like patients with diabetes needing insulin.” 

Real Cause of Depression Is Typically Ignored

According to Gøtzsche, there is no known mental health issue that is caused by an imbalance of brain chemicals. In many cases, the true cause is unknown, but “very often, it is a response to unhealthy living conditions,” he writes.11

He also cites the book,12 “Anxiety — The Inside Story: How Biological Psychiatry Got It Wrong,” written by Dr. Niall McLaren, in which the author shows that anxiety is a major factor in and trigger of most psychiatric disorders.

“A psychiatrist I respect highly, who only uses psychiatric drugs in rare cases … has said that most people are depressed because they live depressing lives,” Gøtzsche writes.

“No drug can help them live better lives. It has never been shown in placebo-controlled trials that a psychiatric drug can improve people’s lives — e.g., help them return to work, improve their social relationships or performance at school, or prevent crime and delinquency. The drugs worsen people’s lives, at least in the long run.13

Gøtzsche rightfully points out that antipsychotic drugs create chemical imbalances; they don’t fix them. As a group, they’re also somewhat misnamed, as they do not address psychotic states. Rather, they are tranquilizers, rendering the patient passive. However, calming the patient down does not actually help them heal the underlying trauma that, in many cases, is what triggered the psychosis in the first place.

As noted in one 2012 meta-analysis14 of studies looking at childhood trauma — including sexual abuse, physical abuse, emotional/psychological abuse, neglect, parental death and bullying — and subsequent risk of psychosis:

“There were significant associations between adversity and psychosis across all research designs … Patients with psychosis were 2.72 times more likely to have been exposed to childhood adversity than controls … The estimated population attributable risk was 33% (16%-47%). These findings indicate that childhood adversity is strongly associated with increased risk for psychosis.”

Economy of Influence in Psychiatry

A related article,15 written by investigative journalist Robert Whitaker in 2017, addresses the “economy of influence” driving the use of antidepressant drugs in psychiatric treatment — and the “social injury” that results. As noted by Whitaker, mental disorders were initially categorized according to a disease model in 1980 by the American Psychiatric Association.

“We’re all familiar with the second ‘economy of influence’ that has exerted a corrupting influence on psychiatry — pharmaceutical money — but I believe the guild influence is really the bigger problem,” he writes.

Whitaker details the corruption within the APA in his book “Psychiatry Under the Influence,” one facet of which is “the false story told to the public about drugs that fixed chemical imbalances in the brain.” Other forms of corrupt behavior include:

  • The biased designs of clinical trials to achieve a predetermined result
  • Spinning results to support preconceived conclusions
  • Hiding poor long-term outcomes
  • Expanding diagnostic categories for the purpose of commercial gain
  • Creating clinical trial guidelines that promote drug use

In his article, Whitaker goes on to dissect a 2017 review16 published in the American Journal of Psychiatry, which Whitaker claims “defends the profession’s current protocols for prescribing antipsychotics, which includes their regular long-term use.”

As Whitaker points out, there’s ample evidence showing antipsychotic drugs worsen outcomes over the long term in those diagnosed with psychotic disorders such as schizophrenia.

The review in question, led by Dr. Jeffrey A. Lieberman, was aimed at answering persistent questions raised by the mounting of such evidence. Alas, their conclusions dismissed concerns that the current drug paradigm might be doing more harm than good.

“In a subsequent press release and a video for a Medscape commentary, Lieberman has touted it as proving that antipsychotics provide a great benefit, psychiatry’s protocols are just fine, and that the critics are ‘nefarious’ individuals intent on doing harm,” Whitaker writes.17

The Scientific Bias of Psychiatric Treatment

Five of the eight researchers listed on the review have financial ties to drug companies, three are speakers for multiple drug companies and all eight are psychiatrists, “and thus there is a ‘guild’ interest present in this review, given that they are investigating whether one of their treatments is harmful over the long-term,” Whitaker notes.18

Not surprisingly, the review ignored studies showing negative effects, including studies showing antipsychotics have a detrimental effect on brain volume. What’s more, while withdrawal studies support the use of antipsychotics as maintenance therapy over the long term, these studies do not address how the drugs affect patients’ long-term health.

“They simply reveal that once a person has stabilized on the medication, going abruptly off the drug is likely to lead to relapse,” Whitaker writes.19 “The focus on long-term outcomes, at least as presented by critics, provides evidence that psychiatry should adopt a selective-use protocol.

If first-episode patients are not immediately put on antipsychotics, there is a significant percentage that will recover, and this ‘spontaneous recovery’ puts them onto a good long-term course. As for patients treated with the medications, the goal would be to minimize long-term use, as there is evidence that antipsychotics, on the whole, worsen long-term outcomes.”

Vast Majority of Psychotic Patients Are Harmed, Not Helped

In his deconstruction of Lieberman’s review, Whitaker details how biased thinking influenced the review’s conclusions. It’s a rather long article, but well worth reading through if you want to understand how a scientific review can be skewed to accord with a preconceived view.

Details I want to highlight, however, include findings relating to the number needed to treat (NNT) and the percentage of patients harmed by the routine use of antipsychotic drugs as a first-line treatment.

As noted by Whitaker, while placebo-controlled studies reveal the effectiveness of a drug compared to an inert substance, they do not effectively reveal the ratio of benefit versus harm among the patient population. NNT refers to the number of patients that have to take the drug in order to get one positive response.

A meta-analysis cited in Lieberman’s review had an NNT of 6, meaning that six patients must take the drug in order for one to benefit from the treatment. The remaining five patients — 83% — are potentially harmed by the treatment. As noted by Whitaker:20

“The point … is this: reviewers seeking to promote their drug treatment as effective will look solely at whether it produces a superior response to placebo. This leads to a one-size-fits-all protocol.

Reviewers that want to assess the benefit-harm effect of the treatment on all patients will look at NNT numbers. In this instance, the NNT calculations argue for selective use of the drugs …”

Antidepressants Are Not Beneficial in the Long Term

While typically not as destructive as antipsychotics, antidepressants also leave a trail of destruction in their wake. A systematic review21 by Gøtzsche published in 2019 found studies assessing harm from selective serotonin reuptake inhibitors (SSRIs) fail to provide a clear and accurate picture of the harms, and therefore “cannot be used to investigate persistent harms of antidepressants.”

In this review, Gøtzsche and colleagues sought to assess “harms of SSRIs … that persist after end of drug intake.” The primary outcomes included mortality, functional outcomes, quality of life and core psychiatric events. In all, 22 papers on 12 SSRI trials were included. Gøtzsche found several distinct problems with these trials. For starters, only two of the 12 trials had a drop-out rate below 20%.

Gøtzsche and his team also note that “Outcome reporting was less thorough during follow-up than for the intervention period and only two trials maintained the blind during follow-up.” Importantly, though, all of the 22 papers came to the conclusion that “the drugs were not beneficial in the long term.”

Another important finding was that all trials either “reported harms outcomes selectively or did not report any,” and “Only two trials reported on any of our primary outcomes (school attendance and number of heavy drinking days).”

Antidepressants Are More Addictive Than Admitted

In a June 4, 2019, article,22 “The Depression Pill Epidemic,” Gøtzsche writes that antidepressant drugs:

“… do not have relevant effects on depression; they increase the risk of suicide and violence; and they make it more difficult for patients to live normal lives.23 They should therefore be avoided.

We have been fooled by the drug industry, corrupt doctors on industry payroll, and by our drug regulators.24 Surely, many patients and doctors believe the pills are helpful, but they cannot know this, because people tend to become much better with time even if they are not treated.25

This is why we need placebo-controlled trials to find out what the drugs do to people. Unfortunately, virtually all trials are flawed, exaggerate the benefits of the drugs, and underestimate their harms.26

Addictive Nature of Antidepressants Skews Results

In his article,27 Gøtzsche reviews several of the strategies used in antidepressant drug trials to exaggerate benefits and underestimate the harms. One little-known truth that helps skew study results in the drug’s favor is the fact that antidepressants tend to be far more addictive than officially admitted. He explains how this conveniently hides the skewing of results as follows:28

Virtually all patients in the trials are already on a drug similar to the one being tested against placebo. Therefore, as the drugs are addictive, some of the patients will get abstinence symptoms … when randomized to placebo …

These abstinence symptoms are very similar to those patients experience when they try to stop benzodiazepines. It is no wonder that new drugs outperform the placebo in patients who have experienced harm as a result of cold turkey effects.

To find out how long patients need to continue taking drugs, so-called maintenance (withdrawal) studies have been carried out, but such studies also are compromised by cold turkey effects. Leading psychiatrists don’t understand this, or they pretend they don’t.

Most interpret the maintenance studies of depression pills to mean that these drugs are very effective at preventing new episodes of depression and that patients should therefore continue taking the drugs for years or even for life.”

Scientific Literature Supports Reality of User Complaints

Over the years, several studies on the dependence and withdrawal reactions associated with SSRIs and other psychiatric drugs have been published, including the following:

In a 2011 paper29 in the journal Addiction, Gøtzsche and his team looked at the difference between dependence and withdrawal reactions by comparing benzodiazepines and SSRIs. Benzodiazepines are known to cause dependence, while SSRIs are said to not be addictive.

Despite such claims, Gøtzsche’s team found that “discontinuation symptoms were described with similar terms for benzodiazepines and SSRIs and were very similar for 37 of 42 identified symptoms described as withdrawal reactions,” which led them to conclude that:

“Withdrawal reactions to selective serotonin re?uptake inhibitors appear to be similar to those for benzodiazepines; referring to these reactions as part of a dependence syndrome in the case of benzodiazepines, but not selective serotonin re?uptake inhibitors, does not seem rational.”

Two years later, in 2013, Gøtzsche’s team published a paper30 in the International Journal of Risk & Safety in Medicine, in which they analyzed “communications from drug agencies about benzodiazepine and SSRI withdrawal reactions over time.”

By searching the websites of drug agencies in Europe, the U.S., UK and Denmark, they found that it took years before drug regulators finally acknowledged the reality of benzodiazepine dependence and SSRI withdrawal reactions and began informing prescribers and patients about these risks.

A significant part of the problem, they found, is that drug agencies rely on spontaneous reporting of adverse effects, which “leads to underestimation and delayed information about the problems.”

In conclusion, they state that “Given the experience with the benzodiazepines, we believe the regulatory bodies should have required studies from the manufacturers that could have elucidated the dependence potential of the SSRIs before marketing authorization was granted.”

A 2019 paper31 in the Epidemiology and Psychiatric Sciences journal notes “It took almost two decades after the SSRIs entered the market for the first systematic review to be published.” It also points out that reviews claiming withdrawal effects to be mild, brief in duration and rare “was at odds with the sparse but growing evidence base.”

In reality, “What the scientific literature reveals is in close agreement with the thousands of service user testimonies available online in large forums. It suggests that withdrawal reactions are quite common, that they may last from a few weeks to several months or even longer, and that they are often severe.”

Antidepressants Increase Your Risk of Suicide and Violence

In his June 4 article,32 Gøtzsche also stresses the fact that antidepressants can be lethal. In one of his studies,33 published in 2016, he found antidepressants “double the occurrence of events that can lead to suicide and violence in healthy adult volunteers.”

Other research34 has shown they “increase aggression in children and adolescents by a factor of 2 to 3 — an important finding considering the many school shootings where the killers were on depression pills,” Gøtzsche writes.

In middle-aged women with stress urinary incontinence, the selective serotonin and norepinephrine reuptake inhibitor (SNRI) duloxetine, which is also used to treat incontinence, has been shown to double the risk of a psychotic episode and increase the risk of violence and suicide four to five times,35 leading the authors to conclude that harms outweighed the benefits.

“I have described the dirty tricks and scientific dishonesty involved when drug companies and leading psychiatrists try convincing us that these drugs protect against suicide and other forms of violence,36 Gøtzsche writes.37 “Even the FDA was forced to give in when it admitted in 2007, at least indirectly, that depression pills can cause suicide and madness at any age.

There is no doubt that the massive use of depression pills is harmful. In all countries where this relationship has been examined, the sharp rise in disability pensions due to psychiatric disorders has coincided with the rise of psychiatric drug usage, and depression pills are those which are used the most by far. This is not what one would expect if the drugs were helpful.”

Drugmaker Lied About Paxil’s Suicide Risk

In 2017, Wendy Dolin was awarded $3 million by a jury in a lawsuit against GlaxoSmithKline, the maker of Paxil. Dolin’s husband committed suicide six days after taking his first dose of a Paxil generic, and evidence brought forth in the case convincingly showed his suicide was the result of the drug, not emotional stress or mental illness.38

The legal team behind that victory, Baum Hedlund Aristei Goldman, is also representing other victims of Paxil-induced violence and death. At the time, attorney R. Brent Wisner said:39

“The Dolin verdict sent a clear message to GSK and other drug manufacturers that hiding data and manipulating science will not be tolerated … If you create a drug and know that it poses serious risks, regardless of whether consumers use the brand name or generic version of that drug, you have a duty to warn.”

GSK’s own clinical placebo-controlled trials actually revealed subjects on Paxil had nearly nine times the risk of attempting or committing suicide than the placebo group. To gain drug approval, GSK misrepresented this shocking data, falsely reporting a higher number of suicide attempts in the placebo group and deleting some of the suicide attempts in the drug group.

An internal GSK analysis of its suicide data also showed that “patients taking Paxil were nearly seven times more likely to attempt suicide than those on placebo,” Baum Hedlund Aristei Goldman reports, adding:40

“Jurors in the Dolin trial also heard from psychiatrist David Healy, one of the world’s foremost experts on Paxil and drugs in its class … Healy told the jurors that Paxil and drugs like it can create in some people a state of extreme ’emotional turmoil’ and intense inner restlessness known as akathisia …

‘People have described it like a state worse than death. Death will be a blessed relief. I want to jump out of my skin,’ Dr. Healy said. Healthy volunteer studies have found that akathisia can happen even to people with no psychiatric condition who take the drug …

Another Paxil side effect known to increase the risk of suicide is emotional blunting … apathy or emotional indifference … [E]motional blunting, combined with akathisia, can lead to a mental state in which an individual has thoughts of harming themselves or others, but is ‘numbed’ to the consequences of their actions. Drugs in the Paxil class can also cause someone to ‘go psychotic, become delirious,’ Dr. Healy explained.”

Hundreds of Thousands of Toddlers on Psychiatric Drugs

Considering the many serious psychological and physical risks associated with psychiatric drugs, it’s shocking to learn that hundreds of thousands of American toddlers are on them. In 2014, the Citizens Commission on Human Rights, a mental health watchdog group, highlighted data showing that in 2013:41

  • 274,000 babies aged 1 and younger were given psychiatric drugs — Of these, 249,699 were on anti-anxiety meds like Xanax; 26,406 were on antidepressants such as Prozac or Paxil, 1,422 were on ADHD drugs such as Ritalin and Adderall, and 654 were on antipsychotics such as Risperdal and Zyprexa
  • In the toddler category (2- to 3-year-olds), 318,997 were on anti-anxiety drugs, 46,102 were on antidepressants, 10,000 were prescribed ADHD drugs and 3,760 were on antipsychotics
  • Among children aged 5 and younger, 1,080,168 were on psychiatric drugs

These are shocking figures that challenge logic. How and why are so many children, babies even, on addictive and dangerously mind-altering medications? Considering these statistics are 6 years old, chances are they’re even higher today. Just what will happen to all of these youngsters as they grow up? As mentioned in the article:42

“When it comes to the psychiatric drugs used to treat ADHD, these are referred to as ‘kiddie cocaine’ for a reason. Ritalin (methylphenidate), Adderall (amphetamine) and Concerta are all considered by the federal government as Schedule II drugs — the most addictive.

ADHD drugs also have serious side effects such as agitation, mania, aggressive or hostile behavior, seizures, hallucinations, and even sudden death, according to the National Institutes of Health …

As far as antipsychotics, antianxiety drugs and antidepressants, the FDA and international drug regulatory agencies cite side effects including, but not limited to, psychosis, mania, suicidal ideation, heart attack, stroke, diabetes, and even sudden death.”

Children Increasingly Prescribed Psych Drugs Off-Label

Making matters even worse, recent research shows the number of children being prescribed medication off-label is also on the rise. An example offered by,43 which reported the findings, is “a doctor recommending antidepressant medication for ADHD symptoms.”

The study,44 published in the journal Pediatrics, looked at trends in off-label drug prescriptions made for children under the age of 18 by office-based physicians between 2006 and 2015. Findings revealed:

“Physicians ordered ?1 off-label systemic drug at 18.5% of visits, usually (74.6%) because of unapproved conditions. Off-label ordering was most common proportionally in neonates (83%) and in absolute terms among adolescents (322 orders out of 1000 visits).

Off-label ordering was associated with female sex, subspecialists, polypharmacy, and chronic conditions. Rates and reasons for off-label orders varied considerably by age.

Relative and absolute rates of off-label orders rose over time. Among common classes, off-label orders for antihistamines and several psychotropics increased over time …

US office-based physicians have ordered systemic drugs off label for children at increasing rates, most often for unapproved conditions, despite recent efforts to increase evidence and drug approvals for children.”

The researchers were taken aback by the findings, and expressed serious concern over this trend. While legal, many of the drugs prescribed off-label have not been properly tested to ensure safety and efficacy for young children and adolescents.

As noted by senior author Daniel Horton, assistant professor of pediatrics and pediatric rheumatologist at Rutgers Robert Wood Johnson Medical School, “We don’t always understand how off-label medications will affect children, who don’t always respond to medications as adults do. They may not respond as desired to these drugs and could experience harmful effects.”

Educate Yourself About the Risks

If you, your child, or another family member is on a psychiatric drug, I urge you to educate yourself about the true risks, and to consider switching to safer alternatives. When it comes to children, I cannot fathom a situation in which a toddler would need a psychiatric drug and I find it shocking that there are so many doctors out there that, based on a subjective evaluation, would deem a psychiatric drug necessary.

You can learn more about the diagnosis and treatment of depression and anxiety in the following articles: “How Exercise Treats Depression,” “Alternative Treatments Effective for Depression,” “Anxiety May Be an Inherited Trait” and “Anxiety Overtakes Depression as No. 1 Mental Health Problem.”

Other Related Health Posts:

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The Opioid Crisis — A Case of Mass Homicide?

Article Source: Health And Fitness Journal

The inappropriate treatment approach to back pain is a driving force behind the opioid epidemic, Dave Chase, co-founder of Health Rosetta, reports,1 citing the 2018 JAMA Network Open paper,2 “Opioid Prescribing for Low Back Pain: What Is the Role of Payers?”

One of the reasons for this is the sheer prevalence of back pain. Statistics3 suggest 8 in 10 American adults will be affected by it at some point in their life.

“It’s also a microcosm of all the things that are wrong with the U.S. health care system, including its contribution to the opioid crisis,” Chase writes.4 “Lower back pain puts people in desperate and vulnerable positions, and it puts doctors under pressure to Do Something Now.

From such a confluence arise many poor and potentially devastating treatments and choices. Among the worst is doctors’ decisions to write opioid prescriptions as a treatment for lower back pain and their patients taking these drugs.

Lower back pain is one of the most common reasons for an opioid prescription,5 but here’s the kicker: There’s no evidence that opioids are effective at treating this problem.”

Opioids Are Inappropriate for Back Pain

Indeed, according to the JAMA paper:6

“Recent data from the first randomized clinical trial with long-term outcomes demonstrated that opioid treatment did not confer benefit with respect to pain-related function and that adverse medication-related events were more common among patients receiving opioid therapy. In contrast, pain intensity was improved among patients randomized to nonopioid treatment.”

Other research7 published in 2018 also shows opioids (including morphine, Vicodin, oxycodone and fentanyl) fail to control moderate to severe pain any better than over-the-counter (OTC) drugs such as acetaminophen, ibuprofen and naproxen.

In fact, those taking nonopioid pain relievers actually fared “significantly better” in terms of pain intensity. Lead author Dr. Erin Krebs with the Minneapolis VA Center for Care Delivery and Outcomes Research (formerly Chronic Disease Outcomes Research), told WebMD:8

“We found that opioids had no advantages over nonopioid medications for pain, function or quality of life in patients with low back pain … This is important information for physicians to share with patients who are considering opioids.”

How Insurance Companies Contribute to the Opioid Crisis

Despite the medical consensus that back pain is best treated with nonpharmacological means, most insurance companies still favor opioids when it comes to reimbursement.

As noted in the American College of Physicians’ guideline9 “Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain,” heat, massage, acupuncture or chiropractic adjustments should be used as first-line treatments. When drugs are desired, nonsteroidal anti-inflammatory drugs (NSAIDs) or muscle relaxants should be used.

Other key treatments include exercise, multidisciplinary rehabilitation, mindfulness-based stress reduction, tai chi, yoga, relaxation, biofeedback, low-level laser therapy and cognitive behavioral therapy.

In a recent episode of Full Measure,10 Sharyl Attkisson interviewed Eileen Kopsaftis, a physical therapist who uses a combination of diet, connective tissue work, proper body dynamics and body balance to address back pain.

As for opioids, they “should only be considered if other treatments are unsuccessful and when the potential benefits outweigh the risks for an individual patient,” according to the American College of Physicians’ guideline.11

Alas, while clinical practice guidelines call for nonpharmacological intervention for back pain, most insurance plans don’t pay for such treatments. They do pay for opioids, though. In his article, Chase explains:12

“That doesn’t make sense until you look at the reason: For the carriers that administer health insurance plans, there is far more profit in pills than physical therapy. (This also explains why the three largest pharmacy benefits managers have recently merged with insurance carriers.)

Our entire health care system is built on a vast web of incentives that push patients down the wrong paths. And in most cases it’s the entities that manage the money — insurance carriers — that benefit from doing so.

They negotiate prices with health systems and pharmaceutical companies, all of which share the objective of increasing revenues, to craft and sell health plans that offer trumped up ‘discounts.’ As long as carriers negotiate a high price with a provider or a rebate scheme with a drug maker, they can still make a sizable profit even after a 50 percent discount.

This dynamic was accelerated by the Affordable Care Act’s Medical Loss Ratio,13 which requires that 80 percent of insurance premium dollars pay for medical expenses and that carriers pocket only 20 percent. It doesn’t take much to see that the higher the premium, the more they make from that 20 percent …

An estimated 700,000 people are likely to die from opioid overdoses between 2015 and 2025,14 making it absolutely essential to understand the connections between insurance carriers, health plans, employers, the public, and the opioid crisis. We will never get out of this mess unless we stop addiction before it starts the opioid crisis isn’t an anomaly. It’s a side effect of our health care system.”

Doctors and Dentists Also Shoulder Blame

Other situations in which opioids are inappropriately prescribed, and massively so, are for tonsillectomies and wisdom teeth extractions.

Insurance claims data from 2016 and 2017 reveal 60% of children between the ages of 1 and 18 with private insurance filled one or more opioid prescriptions after surgical tonsil removal,15,16 and dentists wrote a staggering 18.1 million prescriptions for opioids in 2017.17

As noted by Ronnie Cohen in a March 2019 article18 in The Washington Post, “until recently, dentists seemed to have had no idea they may have been helping to feed an epidemic that resulted in a record 70,237 U.S. drug overdose deaths in 2017.”19

Andrew Kolodny, co-director of opioid treatment research at Brandeis University, told Cohen:20 “It’s almost a rite of passage in the United States having your wisdom teeth out. The aggressive prescribing of opioids to adolescents may be why we’re in an epidemic.”

While American family doctors prescribe an estimated 15% of all immediate-release opioids — the type most likely to be abused — dentists are not far behind, being responsible for 12% of prescriptions, according to a 2011 paper21 in the Journal of the American Dental Association.

According to a JAMA report22 published August 2018, opioids are “routinely” prescribed for wisdom tooth extractions. The Washington Post cites a 2004 survey, which found 85% of oral surgeons prescribe opioids after the removal of wisdom teeth.23

This practice is highly questionable, considering there’s no medical reference showing opioid pain relievers are more effective for this kind of post-surgical pain than NSAIDs.24

On the contrary, an April 2018 medical review25 found a combination of ibuprofen and acetaminophen offered the greatest pain relief, while opioids and opioid combinations had the highest number of adverse events in both children and adults.

Mind you, even though the ibuprofen/acetaminophen combination is less addictive, it can still cause serious potential complications if taken long term, so you also need to be careful when using these drugs and make sure to address the foundational cause of your pain.

Common sense would tell you this practice is putting youth at significant risk for addiction. Research26,27 confirms such suspicions, showing 6.9% of those receiving an opioid prescription from their dentist in 2015 were still using opioids between three and 12 months later. Among those who did not get an initial opioid prescription, only 0.1% sought an opioid prescription in the 12-months that followed.

The American Dental Association now urges dentists and oral surgeons to limit opioid prescriptions for acute pain to a maximum of seven days.28 In a 2018 article29 in The Philadelphia Inquirer, Dr. Rima Himelstein, an adolescent medicine specialist, urges parents whose children are undergoing oral surgery to:

Be the gatekeeper for medications, including those prescribed after wisdom teeth extraction. Don’t just hand your teen the bottle of pills after surgery. And be sure to properly dispose of leftover prescription drugs …”

Johnson & Johnson’s Role in the Opioid Crisis

While Purdue Pharma and the Sackler family appear to have played a central role in the creation of the opioid crisis, few opioid makers and distributors are free of blame. An August 27, 2019, article in The New York Times30 highlights the influence of Johnson & Johnson, a leading supplier of opioid ingredients.

August 26, 2019, Johnson & Johnson was ordered to pay Oklahoma $572 million for violating state public nuisance law, thereby causing decades of opioid addiction and opioid-related deaths in the state.31,32 As reported by The New York Times:33

“The judge cited the company’s overly aggressive marketing tactics: Sales representatives were coached to avoid the ‘addiction ditch’ — the negatives associated with drug use and dependence — when encouraging doctors to prescribe opioids for patients with moderate to severe pain …

Its marketing tactics followed a similar playbook to one Purdue and other opioid manufacturers were employing, and also included so-called unbranded promotion, which was not tied to specific products and encouraged doctors to continue to prescribe more opioids.

Like its competitors, Johnson & Johnson sought to persuade doctors that pain was under-treated, training sales representatives to use ‘emotional selling’ to get across the idea that patients were being harmed by undertreatment.

Another concept was ‘pseudoaddiction,’ or the idea that if patients were asking a doctor for higher doses, they were not necessarily addicted but needed more of the drug to treat their pain.”

According to The New York Times, 326 million opioid pills were dispensed in Oklahoma in 2015 alone, “enough for every adult in the state to receive 110 pills.”34 Oklahoma prosecutors also stressed that were it not for Johnson & Johnson, OxyContin would not have become a blockbuster drug.

In 1994, when Purdue Pharma sought Food and Drug Administration approval for OxyContin, Johnson & Johnson’s supplier subsidiary Tasmanian Alkaloids developed a novel type of opium poppy, the Norman Poppy, which produces higher amounts of thebaine, the active painkilling ingredient in OxyContin.

An Important Break in the Kentucky Case Against Purdue

Purdue is still in the news, though, and chances are we’ll hear a lot more about it in coming weeks and months. The reason for this is because the Kentucky Supreme Court has finally ruled that sealed court records detailing the company’s marketing of OxyContin are to be unsealed and made public.

The cache is also said to include internal reports on the results of clinical trials, communications relating to previous legal cases, and a 2015 deposition of Dr. Richard Sackler. All of these documents were obtained during legal discovery in a lawsuit where Kentucky sued Purdue over the illegal marketing of OxyContin.

The case was settled in 2015, with Purdue being ordered to pay the state $24 million. Part of the settlement agreement called for the destruction of 17 million pages of litigation records held by the state attorney general’s office. Copies of some of the files, however, ended up being placed under seal in a Pike County courthouse. On August 26, 2019, STAT news reported:35

The decision is a major victory for STAT, which first filed a motion36 to unseal the records in March 2016. Purdue has fought to keep the documents out of view, but the Supreme Court’s refusal is final and can’t be appealed.

Now, the public stands to get a glimpse of new information about how Purdue promoted OxyContin and what executives knew about the risk of addiction that came with the drug.

‘The case against Purdue was one of our first decisions when we launched STAT, and we’re thrilled that the trove of documents will finally be made public,’ said John W. Henry, the owner and publisher of STAT.

‘As the opioid crisis continues to devastate communities across the country, it is vital that we all have more answers to so many outstanding questions about the genesis of the epidemic and Purdue’s aggressive marketing of OxyContin.’”

FDA Advisory Panel Riddled With Conflicts of Interest

In related news, The BMJ recently published an editorial37 highlighting a recent BMJ investigation38 that revealed the National Academies of Sciences, Engineering and Medicine (NASEM), which advises FDA on opioid policies, has a number of hidden conflicts of interests, and this too may have played a role in the opioid crisis.

Among these undisclosed conflicts of interests was the fact that Victor Dzau, one of NASEM’s presidents, “had financial ties to Medtronic, a company that sells an implantable device to deliver pain medicine, until last year.”

What’s more, 7 of 15 academics serving on the NASEM panel that advised the FDA on opioid prescribing guidelines had ties to industry. On top of that, NASEM itself accepted $14 million from the Sackler family. The BMJ reports:39

“NASEM responded40 to The BMJ’s investigation to say that it was reviewing its conflict of interest policies and its funding from the Sacklers. It said that it considers only ‘current’ financial ties; but past ties, particularly if recent, substantial, or longstanding, are also conflicts of interest, which is why journals like The BMJ ask authors for disclosures going back three years.

NASEM said that Dzau had complied with its policies; but requiring the public disclosure of all competing interests is essential if policy makers, practitioners, and patients are to be fully informed of how NASEM drafts its guidance.

NASEM said that the $1m of shares Dzau held for previous Medtronic board membership while president of the National Academy of Medicine were managed by his bank without his involvement; but still they constituted a substantial and undeclared conflict of interest because Dzau stood to gain if their worth rose.”

Will Justice Be Done?

In an August 29, 2019 article41 in The Atlantic, Dr. James Hamblin addresses the lack of justice currently on the table:

“The role of marketing in the pharmaceutical industry — the apparatus that profits more from maximizing use than optimizing outcomes — is at an inflection point. A reckoning could lead to serious reform.

But a settlement deal currently on the table — in which Purdue Pharma … would pay about $11 billion42 — stands to repeat the mistakes of the past …

Several billion would come in the form of medications to help treat opioid addiction and overdoses. The Sackler family … would give up ownership of the company, which would file for bankruptcy and become a ‘public beneficiary trust’ …

But no new ground would be broken if the justice comes in the form of fines for what amounts to serious crimes. In 2018, President Donald Trump proposed the extreme measure of using the death penalty for certain drug traffickers and dealers …

Trump did not suggest that these dealers simply pay back a portion of their profits. The importance of sending a message is rarely invoked when it comes to white-collar crime. When drug dealing is done by corporations, the punishment is to impose fines, and to debate what sort of punishment would be fair and productive.

In this case, the proposal on the table would require Purdue to pay a fraction of the $35 billion in profits it claims to have made from Oxycontin — and far less than even the conservative estimates of the damage it caused … estimated in a 2017 White House report to be $504 billion.”

A Moral Reckoning Is Needed

I couldn’t agree more with Hamblin’s assertion that a settlement — and especially one that falls so short of the actual cost to society — will do nothing to change the drug industry’s ways.

“It is not a criminal prosecution. It is not a moral reckoning,” Hamblin writes, and indeed, without criminal prosecution of corporate executives who played an active part in the decisions that were made, the current trend of reckless malfeasance is bound to continue.

In 2007, Purdue pleaded guilty to charges that it misled doctors and patients about OxyContin’s addictive potential and paid $634 million in fines. They knew they were killing people, and the fine did nothing to realign the company’s moral compass. Purdue kept up the same shady practices — putting profits above public health — for another 12 years, bringing us to where we are today. As Hamblin so aptly states:43

“The job of the courts and regulatory apparatus is to help prevent future disaster. This will not happen when penalties are meted out such that loss of life is treated as a cost of doing business.

The Justice Department could impose a criminal framework on concealing information that led to thousands of deaths. There could be consequences … that make it clear to current and future sellers of dangerous products that this can never happen again.”

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The revolutionary science of aging and longevity

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David Sinclair, Ph.D.,1 is a professor of genetics and co-director of the Paul F. Glenn Center for the Biology of Aging at Harvard Medical School. Generally recognized as one of the thought leaders in the science of how to improve our life span and health span, Sinclair earned his Ph.D. in Sydney, Australia.

After working with Leonard Guarente at Massachusetts Institute of Technology as a postdoctoral researcher, he got his own lab at Harvard in 1999, where he’s been teaching aging biology and translational medicine ever since. Sinclair has also written a book, “Lifespan: Why We Age — and Why We Don’t Have To,” which is scheduled for publication on September 10, 2019.

Fasting is part of the longevity solution

Sinclair’s book covers several important strategies that can help slow down the biological clock, including calorie restriction and intermittent fasting. Two of the scientifically demonstrated benefits of fasting are the suppression of mammalian target of rapamycin (mTOR) and the activation of autophagy.

As noted by Sinclair, while fasting itself is not revolutionary, having roots dating back more than 5,000 years, what’s revolutionary “is the discovery of the biochemical pathways that underlie this protection against disease and aging.” Like me, he’s a fan of time-restricted eating, where he simply skips one meal (breakfast) each day.

“There are other diets that other people have found to be effective in terms of improving biology and biochemical markers,” Sinclair says. “One is the 5:2 diet … That one is also quite doable …

More extreme are those diets where you [fast] for a whole week every couple of months or every few months … My view is that that’s probably going to work the best if you can do it, because it doesn’t just trigger the short-term pathways that we’ve been studying in my lab.

A week of fasting will really [trigger] the body to start consuming its own protein … That’s what autophagy is. It’s the consuming of biological material, which is typically protein. In talking with people who’ve done these fasting regimens, after about three days, something different starts to kick in. People who try this tell me that they have a feeling of euphoria. They definitely get an added boost …

We’ve been studying in my lab for the last 20 years genes that respond to diet, to fasting and calorie restriction. The upshot of it is that our bodies respond to adversity or perceived adversity. They turn on these defensive pathways. It changes a bunch of genes that switch on to defend our bodies …

These defenses of the body are extremely good at protecting us against diseases — from diabetes to cancer, heart disease, even dementia and Alzheimer’s. These are things that modern medicine has struggled to combat. This seems to be a very simple way to get the body to fight those diseases.”

At what age should you start fasting?

As for when to start, animal studies suggest the younger you are when you start, the better. For humans, this would of course have to be done within reason. It would be downright foolhardy to put an infant on a fasting regimen, for example.

Teens and young adults in their 20s are also not candidates for fasting, Sinclair says, as “There’s still a lot going on in their bodies and their brains.” After the age of 30, however, extrapolations from animal studies suggest the longer you’re able to incorporate some form of regular fasting across your life span, the better.

As a general rule, intermittent fasting involves fasting for 12 to 16 hours a day, which will typically necessitate eliminating either breakfast or dinner. If you eat dinner, you’ll want to make sure you do it early enough — at least three hours before bedtime. I try to eat my last meal three to six hours before bed.

One of the reasons for this advice is because avoiding late-night eating will increase your nicotinamide adenine dinucleotide (NAD+) levels, which are important for a variety of bodily functions.

Importantly, it will also reduce nicotinamide adenine dinucleotide phosphate (NADPH), which is essentially the true cellular battery of your cell and has the reductive potential to recharge your antioxidants. The largest consumer of NADPH is the creation of fatty acids.

If you’re eating close to bedtime, then you’re not going to be able to use the NADPH to burn those calories as energy. Instead, they must be stored some way. To store them, you have to create fat, so you’re basically radically lowering your NADPH levels when you eat late at night because they are being consumed to store your extra calories by creating fat.

“I tend to snack at night, so it’s my downfall,” Sinclair says, “but yes, to be able to have that fast overnight, that’ll boost your NAD and NADPH levels. These are all good things. They turn on the enzymes that we study called sirtuins. They need NAD to function. You can use the whole night to ostensibly repair your body and protect it from what happens during the day.”

Everything in moderation

An important part of Sinclair’s book delves into the balance between anabolism — the building of muscle tissue — and catabolism, the tearing down and repair of muscle. Counterintuitively, when you fast, growth hormone levels increase, even though there are not nutrients available. Sinclair explains:

“Insulin-like growth hormone (IGF-1) and growth hormone itself, in the short run, don’t seem to be healthy, at least in animal studies. Nir Barzilai of Albert Einstein College of Medicine has studied centenarian families. What he’s found, in particular [in regard] to IGF-1, is that some families can have high levels of IGF-1 but still live a long time.

The reason for that is that they don’t have the IGF-1 receptor as active … [I]f you’re not responding to these hormones, it doesn’t really matter how much your body produces. It’ll still have an effect that mimics the benefits you want. It’s interesting actually that the growth hormone is stimulated by fasting … I’m unaware of exactly why.

But we know that fasting doesn’t lead to bigger animals. It’s actually the opposite. It could be — now I’m just speculating, but I think it’s worth discussing and thinking about — that the short-term bursts of hormones may help the body recover from injury. But those little spikes don’t last long so that you’re not having any downsides …

If I was to summarize everything that I’ve learned over the last 30 years: ‘Everything in moderation, and don’t do anything too consistently.’ … Your body needs to be primed and then allowed to relax; challenged and then allowed to relax.

These diets and these growth hormone spikes, I think they’re good. You just don’t want them on all the time, because then your body doesn’t have a chance to recover and you don’t get the long-term benefits.”

The case for exercising in a fasted state

A tangent to this is the idea that the ideal time to do strength training is right before you have your first meal after a 16- or 18-hour fast. In other words, exercising while still fasting.

The reason for this is because your growth hormone is already activated, allowing you to reap maximum benefit from the anabolic stress of the exercise, which increases peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1?) and mitochondrial biogenesis. As noted by Sinclair, this is “the cutting edge of thinking.”

“Again, in the full disclaimer, we’re discussing the cutting edge of science, so we don’t fully know the answers to this. But what makes sense to me is that we don’t want too much protein in our lives. We don’t want to eat a steak at every meal.

Because what we’ve learned through the work of David Sabatini and many others in the field is that … inhibiting the mTOR pathway by having a lack of certain amino acids is healthy and does lengthen lifespan in animals.

But does that mean that you shouldn’t eat protein? Absolutely not. There are times when eating proteins is important. Same for testosterone. Same for growth hormone. Now we’re getting into the nitty-gritty. If you are pulsing these things, when do you do them together and when do you do them apart?

Let me talk about what I do personally, because that’s actually a better way to approach the discussion. If I’m going to have a steak — I try to be a vegetarian — but let’s say I’m going to have a protein shake, I’m going to do that just before or just after I’ve exercised.

But then I’m also going to have a period in the week where I don’t have a lot of protein … I think … that a little bit of stress every day and a lot of stress once in a while is a great combo.”

The importance of NAD boosters

In his book, Sinclair also discusses the importance of glycine, the shortest and most common amino acid in your body. In the past, people got plenty of glycine from eating bone broth and connective tissue, but most people today are not in the habit of eating homemade bone broth.

As a result, many are not getting enough. Unfortunately, glycine is all the more important these days, as our fructose consumption has dramatically increased. Sinclair explains:

“This is a big question in my field. Just to take a step back, my field and a lot of what my book is about is [about how] to trick the body into [thinking it’s] hungry and having exercise. One of the molecules that does that is NAD.

NAD stands for nicotinamide adenine dinucleotide and we have it in our body. As we exercise and get hungry, it goes up. As we get older, it goes down. It’s needed for life. It’s also needed for turning on these defensive enzymes called sirtuins.

Now, to raise NAD levels, what we’ve done in my lab to mice for the last decade is we give them precursors to NAD. We give them molecules like nicotinamide riboside, or NR, or nicotinamide mononucleotide, also known as NMN …

When times are tough, we’re hungry or we’ve exercised, NAD levels will go up and turn on these defenses. That’s why when you take a molecule like NMN … what we think is happening is that you’re tricking your body into thinking that it’s [had] exercise or that it’s hungry, because the NAD levels will go up.

So, you get the protective benefits … without actually having to necessarily exercise or diet … NMN is what I take each day. I take a gram of it. The thing with NMN is that it has this nicotinamide group on it. It hangs off the main part of the chemical and it’s the first bond to break. We see in animals and even in humans that the levels of nicotinamide go up quite rapidly after taking NMN or NR.

Too high a level of nicotinamide is not good, in part because the nicotinamide gets excreted through the kidneys. That happens because it becomes methylated into methyl nicotinamide. Methyl nicotinamide had been used for years as a marker of all sorts of things …

But the concern … is, ‘Is this drain of methyl nicotinamide a problem?’ The methyl groups are needed for the body. We need methyl for a whole range of things, including antioxidants. As a precaution, I take trimethylglycine so that I continue to give my body a source of methyl groups …

I take it as a precaution because I know that trimethylglycine is not going to hurt me … The other thing is trimethylglycine, also known as betaine, is very good for [human cells], including protecting them against stress. I don’t see any downside … The upside is that I’m preventing my body from being drained of methyl groups.”

None of this is to say you’ll be able to simply take a supplement or two and live a long life while eating junk food and being inactive. They can improve your condition if you’re overweight and don’t exercise, but they’re not a panacea or replacement for a healthy diet and lifestyle.

However, when added to a low-calorie diet and healthy lifestyle, NAD boosters such as NR and NMN do appear to have a magnifying effect, allowing you to really maximize your benefits.

There are other NAD boosters beside NR and NMN, and open questions regarding methods of administration of NR and NMN that may influence their efficacy. All of that is discussed in the interview so, for more details, please listen to it in its entirety, or read through the transcript. I go into detail as to why I believe using the NAD+ molecule itself is likely a far better strategy than using precursors. It is what I am currently doing for my own program.

The theory of xenohormesis

Sirtuins, which much of Sinclair’s studies are focused on, are proteins that act as environmental stress sensors and are responsible for longevity. In simple terms, you could refer to them as longevity proteins. Evidence suggests sirtuins work by suppressing DNA expression. As explained by Sinclair, activating sirtuins is one way to increase longevity in yeast and worms.

One compound found to activate sirtuins is resveratrol. However, once activated, sirtuins require NAD+ as a co-enzyme, and if it isn’t available, it won’t work. Sinclair and his team screened about 18,000 compounds to identify activators, and found you need the SIRT1 gene for it to work — it’s not just an antioxidant effect.

“We published 21 activators in that first paper in the Nature journal, 2003. Resveratrol was the best one we had at the time. It got the most attention because the red wine story was pretty funny and interesting to the media. But there were others that were very close to resveratrol in structure and potency.

Quercetin and fisetin are plant molecules as well. They’re all produced in response to stress … dehydration or ultraviolet (UV) light. They seem to have benefits on organisms [that] consume them.

Interestingly, what has later been discovered, though rarely acknowledged, is that these same molecules work on killing senescent cells … the ‘zombie cells’ that accumulate in your body and cause havoc. Now, others have shown that quercetin … have senolytic properties, same with fisetin. But what’s not recognized typically, or admitted, is that these molecules were discovered 15 years ago to also be SIRT1 activators …

The hypothesis Dr. Konrad Howitz and I came up with, which we published in Cell [in] 2005 … is called xenohormesis. It’s the idea that we’ve evolved to sense our environment, and molecules produced by plants and bacteria in our environment when they’re stressed.

If we consume those or put them on our skin, for example, our bodies will recognize those. We’ve evolved to sense our world around us. That’s a very good way of getting a heads up if your plants are running out of nutrients or the water table is drying up …

That can explain why so many molecules from the plant world have given rise to medicines and why some molecules, like resveratrol and quercetin, fisetin, even aspirin, have remarkable health benefits and target many different enzymes in the body that seems to be well beyond what coincidence could explain …

It’s thought that a little bit of heat, a little bit of cold, a little bit of hunger, some exercise, some hypoxia, lack of oxygen in your body, these are all ways of activating these defense pathways … such as sirtuins … the mTOR, which lower amino acids, particularly leucine and arginine, and the AMPK pathway … these are the main three defensive pathways. There are others.

But what’s downstream of these pathways are things like heat-shock proteins and transcription factors that turn on DNA repair enzymes … Here’s the good news: We used to think we had to understand everything those sensors do to be able to understand aging and be able to live longer.

But what I’ve been arguing for many years now is that we don’t need to fully know what they do … As long as we can find the right nodes in the cell, to turn them on in the right ratios at the right time, the body has evolved to take care of the rest.

We’re getting to the point … where we know what these nodes are. We have the tools to tweak them. We can also change them naturally by fasting and exercising. We can change them with molecules that we can ingest or inject. But now, the cutting-edge is, when do you apply them, how much and in what combinations? That’s really what people like myself … are onto right now.”

The importance of DNA repair

Another strategy for increasing NAD+ is to avoid things that use it up, such as exposure to electromagnetic fields (EMFs). One of the primary DNA repair enzymes inside your cells is poly-ADP ribose polymerase (PARP). PARP is repairs single- and double-stranded DNA breaks and, in so doing, it will use up 100 to 150 NAD molecules for each break.

The more DNA breaks you have, the more NAD is being used up in the repair process. EMF exposure activates PARP and decreases NAD. So, by limiting EMF exposure, you can, by default, increase your NAD, simply because you’re not activating PARP as much.

“PARP enzymes are DNA-repair protein. The problem is when you hyperactivate this protein … There are actually more than 14 different PARPs. They do drain NAD quite effectively. In fact, in my lab, we’ve discovered another PARP that, when you have inflammation, drains NAD as well. It does make sense to slow them down … and in some cases, inhibit … their overuse of NAD,” Sinclair says.

Again, the best way to do that is by avoiding insults, such as EMFs, that activate the PARPs. “Then you get the benefits of low DNA damage and the benefits of high NAD,” Sinclair says, adding:

“Long story short, you want to activate PARP, but not too much … [Even] more interesting, I think, is how do you keep your levels of DNA double-strand breaks to a minimum? I think that’s one of the main keys to longevity.

There are two reasons: One is that double-strand breaks drain NAD. The second … is the idea that DNA double-strand breaks also disrupt the cell’s epigenome, the storage of the information that we get passed down from our mothers and fathers, mother and father, and the packaging of the DNA …

Basically, what happens is, if you have a broken DNA, proteins such as the sirtuins will leave their normal sites where they’re regulating genes and go help repair with PARP. But then they don’t all find their way back to where they came from. Some of them get lost and distracted.

Over time, what we see is that these proteins that are essential for maintaining cellular identity and function will be lost. We see that in yeast cells. Yeast cells get old because they’re moving between breaks and back again to genes.”

The epigenetic noise of aging

One of the most fascinating aspects of Sinclair’s book is the section on how to resolve some of this epigenetic damage, which accumulates through aging. Using the clustered regularly interspaced short palindromic repeats (CRISPR) technique, certain transcription factors were spliced into blind mice, thereby restoring their vision through epigenetic resurrection. Sinclair explains:

“This is a sneak preview of what, hopefully, will be published later this year … We’ve discovered what we think is very strong evidence for … epigenetic noise as a cause of aging … What does that mean?

Let’s just quickly do a biology lesson for those who haven’t been in high school for a while … [The] epigenome is the organization of DNA. The epigenome tells the cell that they should turn on this gene to be a nerve cell, and in a liver cell … Cells inherit that [epigenetic] information just as much as they inherit their DNA.

In my book, what I’m proposing is that … genomic and epigenomic information are quite different. The genomic, the DNA, is ‘digital,’ which is very well-preserved and can last a long time. We know that DVDs last longer than cassette tapes.

The problem for the epigenome is that it’s ‘analog’ information. Anyone who’s had a cassette tape or a record knows that you can pretty easily scratch these or lose the information. You can [also] scratch a DVD and lose the information.

We think aging is similar to those scratches; that the information to be young again is still largely in our bodies. Our cells can access that information by metaphorically polishing the DVD … so the cell can read the right genes …

With that in mind, let me explain what we’ve discovered. We have a metaphorical way of scratching a mouse’s epigenome: We cut the DNA. We create these double-strand breaks [and] let the cell heal … so there’s no change to the digital information. But what we see is the process of proteins moving around and trying to repair that DNA.

It eventually introduces this epigenomic noise, and the genes that were once on, many of them get turned off. Those that were once off come on. Liver cells start to lose their identities. Skin cells start to lose their identity. The consequence, we think, is aging.

We will hopefully publish a paper that shows that if you create this noise in a mouse, it will go through accelerated aging … Second of all, we have mice now that we can change the rate of aging in … The third thing is if you can give an animal something, then you can, with that knowledge, take it away. That’s what we’ve done …

We wanted to reprogram cells. The genes that were … on, now they go back off and vice versa … What we find is that by using these three Yamanaka factors, you can find the original information in the cell that tells it to be young again.

Those genes switch, and the cell behaves like it’s young again. In the case of the retina, we have preliminary results [showing] we can restore eyesight by rejuvenating the nerves in the retina to be young again.”

More information

Eventually, Sinclair’s goal is to identify ways to reprogram all cells in the body, such that they not just act younger but literally are younger on a molecular level. “In my career, I’ve seen a lot of cool stuff. I haven’t seen anything this cool before,” he says. Clearly, there’s extraordinary potential to extend the human life span beyond the current 120 limit.

In his book, he proposes there’s no built-in biological requirement for death, and that, theoretically at least, you could live hundreds of years. To learn more about Sinclair’s research, and the science behind aging and the potential for reversing aging, be sure to pick up a copy of his book, “Lifespan: Why We Age — and Why We Don’t Have To.”

“We could see a world where people do choose to be genetically modified,” Sinclair says. “It’s their choice, right? I don’t think we can easily go in and modify children even though that’s now being done, unless it’s life-threatening, of course. But adults know that they should be able to have a choice if they’re safe and it’s approved, then they should be able to do that.

Maybe there will be a day when we are able to carry these Yamanaka genes in our body. And when we get sick or we have an injury … then we get an IV that turns on those genes for a month. We recover and rejuvenate, then we turn them off again until we need them again. That would be a pretty wild sci-fi future, but both signs are pointing to at least the biology being possible …

I hope people who read the book come away with a new view of what’s possible. Some people who have read it tell me that it’s changed the way they look at their own lives. That’s what I wanted to do. I think we forget how important this topic is, that we can do things right now to alter the course of our lives.”

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