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Millions of people take acetaminophen, commonly known as the brand name drug Tylenol, frequently. People use acetaminophen for treating everything from fevers and muscle aches to headaches, hangovers and other pain. Because acetaminophen is available over the counter and is an ingredient found in many other preparations such as those for cold and flu, few people think twice about taking it. They should.
Acetaminophen is the top cause of acute liver failure in the U.S.1 and overdoses are a leading cause of emergency department visits and hospitalizations.2 According to UT Southwestern Medical Center, more than 200 people a year die from acetaminophen poisoning in the U.S. and there are 15,000 hospital visits due to accidentally taking too much.3
Acetaminophen is also correlated with serious side effects4 such as certain skin conditions, abdominal and gastrointestinal problems and allergic reactions. As I mention later in this article, it also could be dangerous for pregnant women. And, if California state regulators are correct, the latest risk to be associated with acetaminophen may be cancer. The regulators are in the process of determining whether to classify acetaminophen as a carcinogen on the Proposition 65 list.
California's Proposition 65, enacted in 1986, requires the state to maintain a list of chemicals known to cause cancer or reproductive toxicity. Businesses are required to provide a warning if the products they sell or use expose the public to chemicals on the Proposition 65 list.5,6
California state regulators reviewed 133 acetaminophen studies in peer-reviewed journals and are considering whether to classify the drug as a carcinogen. They will hold a public hearing in spring 2020. According to The Associated Press, acetaminophen is:7
" … known outside the U.S. as paracetamol and used to treat pain and fevers. It is the basis for more than 600 prescription and over-the-counter medications for adults and children, found in well-known brands like Tylenol, Excedrin, Sudafed, Robitussin and Theraflu. Acetaminophen has been available in the U.S. without a prescription since 1955.
Concerns about its potential link to cancer come from its relationship to another drug: phenacetin. That drug, once a common treatment for headaches and other ailments, was banned by the FDA in 1983 because it caused cancer."
Since the drug is so popular, some fear that a warning will unnecessarily worry the public but Thomas Mack, chairman of the Carcinogen Identification Committee, the group appointed by the governor to identify chemicals linked to cancer,8 dismisses the fears. "That’s not what our mandate is," he says.9
In addition to the tremendous popularity of acetaminophen, inclusion of a chemical on the Proposition 65 list can pave the way for lawsuits, so industry is resisting the classification.10 For example, reports The Associated Press:
"After the state listed glyphosate — widely known as the weed killer Roundup — as a carcinogen in 2017, a jury ordered the company that makes Roundup to pay a California couple with cancer more than $2 billion. A judge later reduced that award to $87 million."
Suspicion of acetaminophen’s carcinogenic potential stems from the fact that it is a major metabolite of phenacetin, a drug connected with cancer more than three decades ago. In 2001, researchers in the International Journal of Cancer wrote:11
"Concern has been raised about the carcinogenic potential of paracetamol (acetaminophen) because it is the major metabolite of phenacetin, which was classified as a human carcinogen by the International Agency for Research on Cancer (IARC) in 1987 and has been withdrawn from the market in most countries …
Because of the established link between phenacetin and malignant tumors of the urinary tract, most epidemiologic studies of paracetamol and cancer have focused on these tumors.
Some of these have reported slightly elevated risks of renal cell cancer or transitional cell cancers of the renal pelvis, ureter or urinary bladder with regular or long-term use of paracetamol, whereas other studies have failed to demonstrate such associations."
Still, the researchers added that they did not find what you would interpret as very strong cancer links with acetaminophen:12
"We found no evidence of an association between use of paracetamol and risk of urinary bladder cancer, but some evidence of an association with upper urinary tract cancers, including cancers of the renal parenchyma, renal pelvis and ureter."
Nearly 20 years later, in January 2020, the Los Angeles Times weighed in on the possible risks and downplayed them, saying the "standards for inclusion" for the Proposition 65 list are so low, even coffee was put on it.13
As I wrote before, acetaminophen is the top cause of acute liver failure in the U.S. It can even be toxic to your liver at recommended doses when taken daily for just a couple of weeks.14 Part of the reason for the risk is that acetaminophen's recommended dose and the amount of the drug that causes an overdose are very close. There is not much margin of safety.
In fact, studies reveal that taking just a little more acetaminophen than the recommended dose over a few days or weeks (referred to as "staggered overdosing") can be deadlier than one large overdose.15 Research in the Journal of Clinical and Translational Hepatology found:16
"Hepatic injury and subsequent hepatic failure due to both intentional and non-intentional overdose of acetaminophen (APAP) has affected patients for decades, and … it accounts for more than 50% of overdose-related acute liver failure and approximately 20% of the liver transplant cases.
… Although APAP hepatotoxicity follows a predictable timeline of hepatic failure, its clinical presentation might vary. N-acetylcysteine (NAC) therapy is considered as the mainstay therapy, but liver transplantation might represent a life-saving procedure for selected patients."
Few people have heard of three serious skin reactions linked to acetaminophen, but they are concerning enough that the FDA issued a warning in 2013:17
"Reddening of the skin, rash, blisters, and detachment of the upper surface of the skin can occur with the use of drug products that contain acetaminophen. These reactions can occur with first-time use of acetaminophen or at any time while it is being taken …
Anyone who develops a skin rash or reaction while using acetaminophen or any other pain reliever/fever reducer should stop the drug and seek medical attention right away.”
The three skin conditions that the FDA warns of are very rare but also life-threatening:
No one knows why acetaminophen can cause these extreme skin conditions and there is no way to predict who may be at risk before they take the drug. Even more concerning, as the FDA points out in its warning, the reactions can occur in someone who has safely taken acetaminophen before.
Acetaminophen is likely not safe to take for women who are pregnant. A study in JAMA Pediatrics found disturbing links between hyperkinetic disorders (HKD), a severe form of attention-deficit/hyperactivity disorder (ADHD), and ADHD itself.18 The study found a 29% increased risk for ADHD in the children whose mothers had used acetaminophen during pregnancy in the first seven years of their lives and a 37% increased risk of being diagnosed with HKD.19
In a 2015 communication, the FDA cited the JAMA Pediatrics ADHD study. It also cited research that found a possible connection between the use of acetaminophen and other drugs called nonsteroidal anti-inflammatories (NSAIDs) and miscarriage but found the evidence inconclusive.20
The fetal exposure of mothers taking acetaminophen during pregnancy may also increase a child's chances of developing asthma.21 Researchers analyzed data from the Norwegian Mother and Child Cohort Study, which includes many mother/child pairs, and found that prenatal acetaminophen exposure was associated with an increased risk of asthma in offspring.22
Finally, use of acetaminophen during pregnancy may cut levels of testosterone in the womb, negatively affecting males, according to research in mice.23 It's possible that this apparent testosterone reduction interferes with the development of the male reproductive system and explains genital birth defects, infertility and testicular cancer, according to other research.24
In addition to harm to male fetuses, a rat study found that the use of acetaminophen or NSAIDs in pregnancy could reduce the size of ovaries and follicles, and if applied to humans, might indicate that it could affect fertility of resulting daughters and granddaughters.25
Acetaminophen may not be safe to take when you are drinking alcohol. Research suggests it can greatly increase your risk of kidney dysfunction — even if the amount of alcohol is small.26 Combining alcohol with acetaminophen was found to raise the risk of kidney damage by 123% compared to taking either of them individually.
Besides alcoholics, young adults are particularly at risk of kidney harm as they're more likely to consume both alcohol and acetaminophen.27
Acetaminophen can also affect the immune system. According to a study in Human Vaccines & Immunotherapeutics,28 infants who received acetaminophen right after getting a vaccination experienced lowered immune response and developed significantly fewer antibodies against the disease they were vaccinated against.
Acetaminophen's anti-inflammatory activity might explain the apparent effects by interfering with the body's immune system antibody response, say the researchers.
Other risks that have been associated with the use of acetaminophen include chronic obstructive pulmonary disease (COPD) and reduced lung function, brain damage, increased blood pressure and hearing loss. Finally, acetaminophen may have psychiatric effects, according to research conducted by University of British Columbia researchers in 2016.29
The researchers found that use of acetaminophen may both lessen the ability of people to recognize errors that they make and their concern about whether or not they have made an error.30
Past research has also revealed subtle cognitive effects associated with acetaminophen use, like a 2010 study that indicated acetaminophen may reduce the pain of social rejection.31 Research also showed that acetaminophen had the ability to blunt both positive and negative emotions.32
Regardless of whether acetaminophen is added to California's Proposition 65 as a carcinogen, there are many reasons to avoid this drug when possible and use it cautiously. Further, there are many pain-relieving herbs and practices that you can use to replace acetaminophen for natural relief.
In decades past, a daily low-dose aspirin regimen was frequently recommended as a primary prevention strategy against heart disease. However, the evidence in support of it was rather weak, and kept getting weaker as time went on.
I stopped recommending daily "baby aspirin" use for the prevention of heart disease over two decades ago, due to the growing evidence of harmful side effects.
The primary justification for a daily aspirin regimen has been that it inhibits prostaglandin production,1 thereby decreasing your blood's ability to form dangerous clots. However, in more recent years, most public health authorities have reversed their stance on the practice of using aspirin for primary prevention.
The U.S. Food and Drug Administration reversed its position on daily low-dose aspirin as primary prevention for heart disease in 2014,2 citing clearly established side effects — including dangerous brain and stomach bleeding — and a lack of clear benefit for patients who have never had a heart attack, stroke or cardiovascular disease.
In 2019, the American Heart Association (AHA) and American College of Cardiology updated their clinical guidelines on the primary prevention of cardiovascular disease,3 spelling out many of the controversial findings on prophylactic aspirin use.
Importantly, studies have found that prophylactic aspirin use in adults over the age of 70 is potentially harmful, primarily due to the increased risk of bleeding in this age group. As noted in one 2009 paper,4 long-term low-dose aspirin therapy nearly doubles your risk for gastrointestinal bleeding.
Older people are, of course, more likely to be at high risk for heart disease, and thus more likely to be put on aspirin therapy. In younger adults, the risks are less clear-cut.
As noted in the AHA guideline, in adults younger than 40, "there is insufficient evidence to judge the risk-benefit ratio of routine aspirin for the primary prevention of atherosclerotic cardiovascular disease."5
That said, the conventional recommendation to avoid a daily aspirin regimen only applies to primary prevention of heart disease in those with no history of heart problems, or those with low or moderate risk for heart disease. As reported by the AHA:6
"The new recommendation doesn't apply to people who already have had a stroke or heart attack, or who have undergone bypass surgery or a procedure to insert a stent in their coronary arteries.
These individuals already have cardiovascular disease and should continue to take low-dose aspirin daily, or as recommended by their health care provider, to prevent another occurrence ..."
While daily low-dose aspirin continues to be recommended for patients who already have heart disease, there's evidence suggesting it may not be an ideal solution for them either.
For example, the WASH (warfarin/aspirin study in heart failure) study7 published in 2004 — which assessed the risks and benefits of aspirin and the blood thinner warfarin in heart failure patients — found those who received aspirin treatment (300 mg/day) actually had the worst cardiac outcomes, including worsening heart failure. According to the authors, there was "no evidence that aspirin is effective or safe in patients with heart failure."
Similarly, a 2010 study8 found older heart disease patients who had a prior history of aspirin use had more comorbidities and a higher risk of recurrent heart attack than those who had not been on aspirin therapy.
Aspirin has also not been proven safe or effective for diabetics, who are at increased risk for heart disease and therefore likely to be put on an aspirin regimen.
For example, a 2009 meta-analysis9 of six studies found no clear evidence that aspirin is effective in preventing cardiovascular events in people with diabetes, although men may derive some benefit.
Another 2009 study10 that examined the effects of aspirin therapy in diabetic patients found it "significantly increased mortality in diabetic patients without cardiovascular disease from 17% at age 50 years to 29% at age 85 years."
On the other hand, it did lower mortality in elderly diabetic patients who also had cardiovascular disease. A meta-analysis11 published in 2010 also concluded aspirin did not reduce the heart attack risk in diabetic individuals.
While the benefits of low-dose aspirin may outweigh the risks for some people, I believe you may be able to achieve similar cardiovascular protection by doing therapeutic phlebotomies.
There's evidence to suggest that the bleeding caused by aspirin may in fact be part of why it lowers your risk of heart attack and stroke, as bleeding will lower your iron level. Aspirin's ability to lower inflammation may be another factor at play.
As shown in a 2001 study,12 people taking seven aspirins per week had 25% lower mean serum ferritin than nonusers. The effect was most marked in diseased subjects, compared to healthy ones. As explained by the authors:
"Atherosclerosis, a primary cause of myocardial infarction (MI), is an inflammatory disease. Aspirin use lowers risk of MI, probably through antithrombotic and anti-inflammatory effects.
Because serum ferritin (SF) can be elevated spuriously by inflammation, reported associations between elevated SF, used as an indicator of iron stores, and heart disease could be confounded by occult inflammation and aspirin use if they affect SF independently of iron status …
Aspirin use is associated with lower SF. We suggest this effect results from possible increased occult blood loss and a cytokine-mediated effect on SF in subjects with inflammation, infection, or liver disease."
Most people, physicians included, fail to appreciate that — aside from blood loss, including menstruation — the body has no significant way to excrete excess iron. There are very minor amounts lost through normal bodily processes, but not enough to move the needle on overall iron levels.
Between supplementation, fortification and the iron that occurs naturally in foods, it's very easy to end up with excessive levels. In fact, most adult men and postmenopausal women are at risk for excess iron and need regular blood testing for ferritin.
Excessive iron causes significant oxidative stress, catalyzing the formation of excessive free radicals that damage your cellular and mitochondrial membranes, proteins and DNA. It is a potent contributor to increased risks of cancers, heart disease and neurodegenerative diseases. You can learn more about the ins and outs of excess iron in "Why Managing Your Iron Level Is Crucial to Your Health."
While dangerous, iron overload is easy and inexpensive to treat. All you really need to do is monitor your serum ferritin and/or gamma-glutamyl transpeptidase (GGT) levels, avoid iron supplements, and be sure to donate blood on a regular basis.
By doing this, you can avoid serious health problems, and donating blood is a far safer way to lower your iron stores than taking aspirin and losing blood via internal bleeding.
Interestingly, a 2019 study13 found prophylactic aspirin use may lower the risk of all-cause cancer, gastrointestinal (GI) cancer and colorectal cancer mortality among older adults.
The study included 146,152 individuals with a mean age of 66.3 years who participated in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The median follow-up time was 12.5 years. Those taking aspirin at least three times a week had a:
Having a higher body mass index (BMI between 25 and 29.9) lowered these percentages by 1%, with the exception of colorectal cancer. In this group, colorectal cancer death decreased by 34%.
No observable benefit of aspirin use was found in underweight individuals (BMI below 20), which led the researchers to hypothesize that "the efficacy of aspirin as a cancer preventive agent may be associated with BMI,"14 although this theory needs to be confirmed in future studies. The authors also warn that prophylactic aspirin therapy for cancer prevention would need to be weighed against the increased risk of bleeding.
Overall, there's a lot of evidence against long-term daily aspirin therapy. The risk of internal bleeding is one significant concern, which is further magnified if you're taking antidepressants or blood thinning medications such as Plavix.
Using aspirin in combination with SSRI antidepressants has been shown to increase your risk of abnormal bleeding by 42%, compared to those taking aspirin alone,15 and taking aspirin (325 mg/day) with Plavix has been shown to nearly double your risk of major hemorrhage and significantly increase your risk of death, while not affecting your risk of recurrent stroke to any significant degree.16
Aside from damaging your gastrointestinal tract,17,18 routine aspirin use has also been linked to an increased risk for cataracts,19 neovascular (wet) macular degeneration,20 tinnitus21 and hearing loss in men.22
Aside from donating blood to lower your iron level (provided it's elevated), nattokinase is another far safer alternative to a daily aspirin regimen. Nattokinase, produced by the bacteria Bacillus subtilis during the fermentation of soybeans to produce natto,23 is a strong thrombolytic,24 comparable to aspirin without the serious side effects.
It's been shown to break down blood clots and reduce the risk of serious clotting25 by dissolving excess fibrin in your blood vessels,26 improving circulation and decreasing blood viscosity. These effects can also help reduce high blood pressure.27
As noted in a 2018 paper,28 nattokinase appears to be a promising alternative in the prevention and treatment of cardiovascular diseases, and has been linked to a reduction in cardiovascular disease mortality.
Yet another alternative is lumbrokinase, a complex fibrinolytic enzyme extracted from earthworms. Like nattokinase, lumbrokinase boosts circulatory health by reducing blood viscosity, reducing blood clotting factor activity and degrading fibrin, which is a key factor in clot formation.29,30
Some researchers have suggested lumbrokinase could be used "as secondary prevention after acute thrombosis," such as heart attacks and stroke.31 A 2008 study32 that explored "the mechanisms involved in the anti-ischemic action of lumbrokinase (LK) in the brain," found it protected against cerebral ischemia via several mechanisms and pathways. As explained by the authors:
"These data indicated that the anti-ischemic activity of LK was due to its anti-platelet activity by elevating cAMP level and attenuating the calcium release from calcium stores, the anti-thrombosis action due to inhibiting of ICAM-1 expression, and the anti-apoptotic effect due to the activation of JAK1/STAT1 pathway."
A 2009 pilot study33 that used lumbrokinase in patients with coronary artery disease and stable angina found it improved angina symptoms in 40% of patients and lowered the summed stress score by 29% (the summed stress score is a risk indicator for a cardiac event over the next 12 months34). According to the authors, "Oral lumbrokinase improves regional myocardial perfusion in patients with stable angina."
In recent years, the devastating effects of wanton opioid use have become unmistakable, with opioid overdoses killing 47,600 Americans in 2017 alone.1 As of June 2017, opioids became the leading cause of death among Americans under the age of 50,2 and President Trump declared the opioid crisis a public health emergency that year in October.3
I've written many previous articles detailing the background of how the U.S. ended up here. While the opioid crisis was largely manufactured by drug companies hell-bent on maximizing profits, leading to exaggerated and even fraudulent claims about the drugs' safety profile, the increased availability of opioids isn't the sole cause.
As noted in a January 2020 article4 in The Atlantic, "researchers … say opioid addiction looks like the result of a perfect storm of poverty, trauma, availability and pain."
Commenting on some of the research cited in that article, David Powell, senior economist at Rand, told The Atlantic that to produce the most lethal drug epidemic America has ever seen "you need a huge rise in opioid access, in a way that misuse is easy, but you also need demand to misuse the product."5
Poverty and pain, both physical and emotional, fuel misuse. If economic stress or physical pain (or both) is a factor in your own situation, please be mindful that seeking escape through opioid use can easily lead to a lethal overdose. The risk of death is magnified fivefold if you're also using benzodiazepine-containing drugs.
Several investigations seeking to gain insight into the causes fueling the opioid epidemic have been conducted in recent years. The findings reveal common trends where emotional, physical and societal factors have conspired to bring us to the point where we are today.
Among them is a 2019 study6 in the Medical Care Research Review journal, which looked at the effects of state-level economic conditions — unemployment rates, median house prices, median household income, insurance coverage and average hours of weekly work — on drug overdose deaths between 1999 and 2014. According to the authors:7
"Drug overdose deaths significantly declined with higher house prices … by nearly 0.17 deaths per 100,000 (~4%) with a $10,000 increase in median house price. House price effects were more pronounced and only significant among males, non-Hispanic Whites, and individuals younger 45 years.
Other economic indicators had insignificant effects. Our findings suggest that economic downturns that substantially reduce house prices such as the Great Recession can increase opioid-related deaths, suggesting that efforts to control access to such drugs should especially intensify during these periods."
Similarly, an earlier investigation, published in the International Journal of Drug Policy in 2017,8 connected economic recessions and unemployment with rises in illegal drug use among adults.
Twenty-eight studies published between 1990 and 2015 were included in the review, 17 of which found that the psychological distress associated with economic recessions and unemployment was a significant factor. According to the authors:9
"The current evidence is in line with the hypothesis that drug use increases in times of recession because unemployment increases psychological distress which increases drug use. During times of recession, psychological support for those who lost their job and are vulnerable to drug use (relapse) is likely to be important."
Abuse-related trauma is also linked to unemployment and financial stress, and that too can increase your risk of drug use and addiction. As noted in The Atlantic,10 when the coal mining industry in northeastern Pennsylvania collapsed, leaving many locals without job prospects, alcohol use increased, as did child abuse. Many of these traumatized children, in turn, sought relief from the turmoil and ended up becoming addicted to opioids.
Another 2019 study11 published in Population Health reviewed the links between free trade and deaths from opioid use between 1999 and 2015, finding that "Job loss due to international trade is positively associated with opioid overdose mortality at the county level," and that this association was most significant in areas where fentanyl was present in the heroin supply.
Overall, for each 1,000 people who lost their jobs due to international trade — commonly due to factory shutdowns — there was a 2.7% increase in opioid-related deaths. Where fentanyl was available, that percentage rose to 11.3%. The study "contributes to debates in the social sciences concerning the negative consequences of free trade," the authors note, adding:
"Scholars have long focused on the positive effect of international trade on the overall economy, while also noting that it causes layoffs and bankruptcy for some groups.
Recent influential work by Autor, Dorn, and Hanson demonstrates that these negative impacts of trade are actually highly localized, with layoffs, unemployment, and lower wages concentrated in specific labor markets.
This study furthers our understanding of the local consequences of international trade by looking beyond wages and employment levels to the potential impact on opioid-related overdose death."
The National Bureau of Economic Research has also contributed to the discussion with the working paper12 "Origins of the Opioid Crisis and Its Enduring Impacts," issued November 2019.
In it, they highlight "the role of the 1996 introduction and marketing of OxyContin as a potential leading cause of the opioid crisis," showing that in states where triplicate prescription programs were implemented, OxyContin distribution rates were half that of states that did not have such programs.
"Triplicate prescription programs" refers to a drug-monitoring program requiring doctors to use a special prescription pad whenever they prescribed controlled substances. One of the copies of each prescription written had to be submitted to a state monitoring agency.
Since it involved additional work, many doctors avoided prescribing drugs requiring the use of triplicates, and as a consequence, Purdue (the maker of OxyContin), did not market its opioid as aggressively in those states.
The fact that triplicate prescription states had lower rates of lethal overdoses led the authors to conclude "that the introduction and marketing of OxyContin explain a substantial share of overdose deaths over the last two decades."
According to this paper, death rates from opioid overdoses could have been reduced by 44% between 1996 and 2017 had triplicate prescriptions been implemented in nontriplicate states.
Importantly, the relationship between triplicate prescription programs and opioid overdose deaths held true even when economic conditions were taken into account, which shows that poverty alone did not contribute to the opioid crisis — aggressive marketing to doctors and the ease with which patients could get the drugs were an inescapable part of the problem.
Naturally, physical pain is also a driving force behind the opioid epidemic, especially the inappropriate treatment of back pain with opioids and dentists' habit of prescribing narcotics after wisdom tooth extractions.13,14
(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 paper15 in the Journal of the American Dental Association.)
Statistics16 suggest 8 in 10 American adults will be affected by back pain at some point in their life, and low-back pain is one of the most common reasons for an opioid prescription.17 This despite the fact that there's no evidence supporting their use for this kind of pain. On the contrary, non-opioid treatment for back pain has been shown to be more effective.18
Research19 published in 2018 found 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, yet most insurance companies still favor opioids when it comes to reimbursement, which makes them culpable for sustaining the opioid crisis, even as doctors and patients try to navigate away from them.
As noted by Dave Chase, author of "The Opioid Crisis Wake-Up Call: Health Care Is Stealing the American Dream. Here's How to Take It Back," in an article for Stat:20
"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 …
An estimated 700,000 people are likely to die from opioid overdoses between 2015 and 2025,21 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."
According to the American College of Physicians' guidelines,22 heat, massage, acupuncture or chiropractic adjustments should be used as first-line treatments for back pain. Other key treatments for back pain include exercise, multidisciplinary rehabilitation, mindfulness-based stress reduction, tai chi, yoga, relaxation, biofeedback, low-level laser therapy and cognitive behavioral therapy.
When drugs are desired, nonsteroidal anti-inflammatory drugs (NSAIDs) or muscle relaxants should be used. Opioids "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.23
It's vitally important to realize that opioids are extremely addictive drugs that are not meant for long-term use for nonfatal conditions. Chemically, opioids are similar to heroin, so if you wouldn't consider using heroin for a toothache or backache, seriously reconsider taking an opioid to relieve these types of pain.
If you've been on an opioid for more than two months, or if you find yourself taking a higher dosage, or taking the drug more often, you may already be addicted. Resources where you can find help include the following. You can also learn more in "How to Wean Off Opioids."
The good news is that many types of pain can be treated entirely without drugs. Recommendations by Harvard Medical School25,26 and the British National Health Service27 include the following. You can find more detailed information about most of these techniques in "13 Mind-Body Techniques That Can Help Ease Pain and Depression."
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Gentle exercise |
Physical therapy or occupational therapy |
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Hypnotherapy |
Distracting yourself with an enjoyable activity |
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Maintaining a regular sleep schedule |
Mind-body techniques such as controlled breathing, meditation, guided imagery and mindfulness practice that encourage relaxation. One of my personal favorites is the Emotional Freedom Techniques (EFT) |
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Yoga and tai chi |
Practicing gratitude and positive thinking |
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Hot or cold packs |
Biofeedback |
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Music therapy |
Therapeutic massage |
In "Billionaire Opioid Executive Stands to Make Millions More on Patent for Addiction Treatment," I discuss several additional approaches — including helpful supplements and dietary changes — that can be used separately or in combination with the strategies listed above to control both acute and chronic pain.
The New York Times1 reports that the average person in their mid- to late 60s today is taking 15 prescription drugs a year — and that doesn’t even count the number of over-the-counter products they may be taking.
That’s a lot of medications, especially when you consider that a survey released by the American Association of Retired Persons (AARP)2 not quite four years ago, in 2016, indicated that 75% of the respondents — all over age 50 — said they take at least one prescription medication on a regular basis.
In that AARP survey, more than 80% reported taking at least two, and more than 50% took four or more. Compared to a 2005 Gallup survey,3 which showed 52% of all Americans said they were taking at least one prescription medication, it’s obvious that seniors are taking more drugs than they did in the past.
Specifically, from 1988 to 2010, adults over age 65 doubled the number of prescriptions they took from two to four.4 The proportion of adults taking five or more tripled in that same time period. Yet, despite the rising number of prescriptions, more drugs don’t add up to better health.
According to the researchers, “Contemporary older adults on multiple medications have worse health status compared to those on fewer medications, and appear to be a vulnerable population.” This translates to a negative effect on activities of everyday living as well as increased confusion and memory problems.
The term used to describe a condition in which a person takes multiple medications, drugs, supplements and over-the-counter remedies is polypharmacy. As evidenced by the quoted research, the clinical relevance and consequences of polypharmacy — of seniors taking fistfuls of medications each day — are far-reaching as the aging population across the world continues to grow.
Polypharmacy is common among the elderly, especially for those who reside in nursing homes. Some end up in a nursing home because of adverse drug reactions, which places financial and emotional burdens on communities and families. They also may result in a significant number of hospitalizations with a high number of complications, increased rates of death and excessive health care costs.5
What’s worse, you may believe the federal government, medical associations or pharmaceutical companies have tested the effects that combinations of drug chemicals would have in your body but, unfortunately, this doesn’t always happen.
Researchers report these adverse drug reactions are responsible for up to 12% of all hospital admissions of seniors. Yet, even being in the hospital doesn’t ensure against, or reduce, polypharmacy.
In one study,6 a team in Italy evaluated 1,332 inpatients who were at least 65 years old and who took at least five medications. They found polypharmacy was present in 51.9% of the patients when they arrived at the hospital; this increased to 67% by the time they left.
One of the hidden dangers of polypharmacy is the chemical interactions that occur in the body when medications are mixed. Another problem is the number of times one drug is prescribed to take care of the side effects of another. This has become known as a “prescribing cascade.” The New York Times writes:7
“One common example is the use of anti-Parkinson therapy for symptoms caused by antipsychotic drugs, with the anti-Parkinson drugs in turn causing new symptoms like a precipitous drop in blood pressure or delirium that result in yet another prescription.”
To that end, drug interactions can cause hospitalizations in and of themselves — and sometimes these interactions can even lead to death. The authors of one study8 noted a 50% increase in this problem when seniors are taking five to nine medications.
Dr. Michael Stern, geriatric emergency medicine specialist at New York Presbyterian Hospital, told a New York Times reporter that polypharmacy accounts for more than one-fourth of all admissions to the hospital and that it would be considered the fifth leading cause of death if it were categorized that way.9
In a study10 published in 2013, scientists looked at participants who were prescribed antidepressants by their physicians. Of those who were over age 65, only 14.3% met the DSM-4 criteria for having had a major depressive episode — indicating they most likely were overprescribed or not necessary. The authors noted the importance of providing better diagnoses to patients as well as more appropriate treatments of their symptoms.
And again, statistics show more prescriptions don’t translate into fewer depressive illnesses. For example, in a 2017 study,11 researchers reviewed data from 1990 to 2015 that had been gathered in England, Canada, the U.S. and Australia and found the incidence of symptoms had not decreased despite an increase in the number of prescriptions of antidepressants.
This is important because the risks associated with depression in seniors include cognitive decline, dementia and poor medical outcomes. Those suffering from depression in any age group also experience higher rates of suicide and mortality.
This is one reason the American Psychiatric Association writes that in some cases, treatment for the elderly “should parallel that used in younger age groups.”12 Unfortunately, even though therapy for depression can include psychotherapy and alternative treatments, such as addressing vitamin deficiencies, good sleep habits, proper nutrition and exercise, too often, seniors are only prescribed medication — and that only adds to the multiple prescriptions they’re probably already taking.
In related studies, researchers have found that inflammation contributes to many chronic diseases including heart disease and dementia.13 They also have found a link between inflammation and depression. The authors of one literature review14 included results from 30 randomized control trials with a total of 1,610 participants. Data analysis showed anti-inflammatory agents could reduce depressive disorder when compared to a placebo.
Results from another large meta-analysis15 revealed similar findings: Anti-inflammatory medications were helpful for those dealing with depression.
Yet another group of researchers16 found that those treated with immunotherapy for an inflammatory disorder experienced symptomatic relief of depressive symptoms. All of this points toward other ways of addressing depression than resorting to a prescription antidepressant. For a discussion of how to reduce inflammation naturally, see the articles below and consider optimizing your melatonin, adding fiber to your diet and grounding.
Before adding one more prescription medication or over-the-counter drug to your daily regimen, consider seeking the help of a natural health physician who can help get to the root of the problem. Too often medications mask symptoms but do not address the underlying condition. A vicious cycle may begin when the first medication triggers a side effect that a second medication will be prescribed to treat.
While your pharmacy computer may flag some drug interactions, the chemical complexity involved when more than three drugs are prescribed make it unnecessarily challenging to avoid adverse reactions. The real solution is to take control of your health and introduce foundational strategies to improve your overall health.
There is no magic pill that will fix symptoms, remove your illness and restore the vigor of youth. However, there are lifestyle choices you can make that will go a long way toward achieving your health goals. Consider starting with the strategies in the following articles to move toward better health:
Depression is common in older adults, occurring in 2% of those aged 55 years and older and rising with increasing age. Many more — from 10% to 15% — struggle with depressive symptoms, although they may not have been diagnosed with major depression.1
That being said, there’s been a major rise in the number of antidepressants being prescribed for older adults over the last two decades, without a similarly sharp increase in the number depressed, according to a study published in The British Journal of Psychiatry.2
The findings suggest seniors may be being overprescribed antidepressant drugs, which could have serious implications for their health, although the researchers weren’t willing to state this, noting instead, "we can't infer that older patients are prescribed antidepressants unnecessarily."3
In order to investigate whether the prevalence of depression and antidepressant drug use changed from 1990 to 2011 in people aged 65 and over, researchers used data from two English population-based cohort studies involving 15,397 people. The studies took place from 1991 to 1993 and between 2008 and 2011.
In the first study group, 4.2% of the adults were taking antidepressants, but this jumped to 10.7% in the later study. During this time, the prevalence of depression decreased, but only slightly, from 7.9% to 6.8%.4 Also noteworthy, among older adults living in care homes, the prevalence of depression was unchanged but the use of antidepressants rose from 7.4% to 29.2%.5
There were a few suggestions offered for why antidepressant prescribing rates increased so steeply without a similar increase in depression, including overdiagnosis or prescribing the drugs for conditions other than depression. However, most of those prescribed antidepressants had not been diagnosed with depression.
Lead study author Antony Arthur, Ph.D. of the University of East Anglia, Norwich, United Kingdom, told Medscape, "Sometimes treatment is given for mild depression which falls outside of our definition of depression ― much of the evidence for the effectiveness of antidepressants is for people with moderate or severe depression. Antidepressants are also used to treat other conditions, for example, neuropathic pain and sleep disorders."6
He added that opportunities to deprescribe antidepressants should not be overlooked.7 “Whatever the explanation, substantial increases in prescribing has not reduced the prevalence of depression in the over-65 population. The causes of depression in older people, the factors that perpetuate it, and the best ways to manage it remain poorly understood and merit more attention,” he stated.8
A separate study, published in World Psychiatry in 2017, reviewed data collected from 1990 to 2015 from Australia, Canada, England and the U.S. It similarly found that “the prevalence of mood and anxiety disorders and symptoms has not decreased, despite substantial increases in the provision of treatment, particularly antidepressants.”
Depression is a serious mental health condition that’s associated with many negative outcomes in older adults. Along with increasing personal suffering, depression is associated with an increased risk of cognitive decline, dementia, poor medical outcomes, suicide and high mortality.9
American Psychiatric Association guidelines suggest optimal treatment for depression should include antidepressant medication along with psychotherapy, but most elderly who are treated for depression (many go without treatment) receive antidepressant medications only.10 Yet, there are a number of risks that come with antidepressant usage.
For instance, antidepressant users have an increased risk of developing Type 2 diabetes,11 even after adjusting for other risk factors, like body mass index (BMI).12 Antidepressant use has also been linked to thicker arteries, which could contribute to the risk of heart disease and stroke.13
The drugs are also linked to dementia, with researchers noting “treatment with SSRIs, MAOIs, heterocyclic antidepressants and other antidepressants was associated with an increased risk of dementia,” and as the dose increased, so too did the risk.14
The drugs are also known to deplete various nutrients from your body, including coenzyme Q10 and vitamin B12 — in the case of tricyclic antidepressants — which are needed for proper mitochondrial function. SSRIs may deplete calcium, folate and other important nutrients from your body.15 There are also risks specific to older adults, which are not necessarily seen in younger adults.
According to research published in Expert Review of Neurotherapeutics, “One particular concern is that antidepressants increase the risk of falls, osteoporosis and fractures … antidepressants have side effects and risks, some of which can be observed acutely while others may be longer-term consequences.”16
For example, one 2015 study found that, compared to perimenopausal women treated with H2 antagonists or proton pump inhibitors (indigestion drugs), selective serotonin reuptake inhibitors (SSRIs, a class of antidepressants) raised bone fracture rates by 76% in the first year of use. After two years of treatment, the fracture rate was 73% higher.17,18
What’s more, between 1988 and 2010 39% of people aged 65 and over were taking at least five prescription medications each day19 — in 2019 as many as 43% may be taking eight or more, while 24% could be taking as many as 10 day,20 which can be contraindicated, raising new risks. In 2015 when the first study was published, researchers believed the increases were driven, in part, by rising use of antidepressant drugs.
Studies have repeatedly shown antidepressants work no better than placebo for mild to moderate depression,21 so seniors may be taking serious risks for a very small chance of benefit.
In yet another study that documented the overprescription of antidepressants in older adults, researchers found they were often prescribed in the absence of major depressive disorder (MDD), although they were not effective for such purposes. Researchers concluded:22
“Providers and the public increasingly recognize depression as a medical problem meriting treatment; however, they should be aware that antidepressants are not beneficial for depressive symptoms that do not meet the criteria for MDD, but their potential side effects and costs remain regardless of whether MDD is present.”
Even in severely depressed patients, the difference in efficacy between antidepressants and placebo has been described as “relatively small,”23 while Irving Kirsch, associate director of the Program in Placebo Studies at Harvard Medical School, has conducted several meta-analyses of antidepressants in comparison to placebo, concluding there’s virtually no difference in their effectiveness.
According to Kirsch, “The difference is so small, it’s not of any clinical importance.”24 In a 2014 article, he wrote:25
“Antidepressants are supposed to work by fixing a chemical imbalance, specifically, a lack of serotonin in the brain. Indeed, their supposed effectiveness is the primary evidence for the chemical imbalance theory.
But analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits are due to the placebo effect.
… Even the small statistical difference between antidepressants and placebos may be an enhanced placebo effect, due to the fact that most patients and doctors in clinical trials successfully break blind … Instead of curing depression, popular antidepressants may induce a biological vulnerability making people more likely to become depressed in the future.”
The seriousness of depression cannot be overstated, and the need for effective treatment is a necessity. However, many seniors may be pinning their hopes of improving their mood and relieving depression on a pill solution that just doesn’t work. Importantly, there are other options available, with exercise being one of them.
In an 11-year study, people who engaged in regular leisure-time exercise for one hour a week were less likely to become depressed.26 A meta-analysis of 33 trials involving nearly 1,877 people also showed that strength training led to a significant reduction in depressive symptoms, and this held true regardless of the participant’s health status, improvements in strength or how much strength training they completed.27
According to the study’s lead author, Brett Gordon, a postgraduate researcher in the department of physical education and sports sciences at the University of Limerick in Ireland, the greatest improvements were seen among people with symptoms of mild to moderate depression, as opposed to those without depression, which suggests strength training may be most effective for people with greater depressive symptoms.28
Research has also looked into the effects of exercise and depression in seniors, particularly. In a study of older depressed adults, 80% experienced a significant reduction in depressive symptoms after taking up strength training for 10 weeks, such that researchers concluded, “PRT [progressive resistance training] is an effective antidepressant in depressed elders, while also improving strength, morale, and quality of life.”29
In yet another study of older adults with depression, those who took part in high-intensity strength training three days a week for eight weeks experienced a 50% reduction in depressive symptoms,30 whereas separate research showed strength training exercise reduced depressive symptoms in older Hispanic/Latino adults as well (endurance, balance and flexibility exercises were also beneficial for mood).31
The upside is that, unlike with antidepressants, which increase health risks, exercise provides additional health benefits to seniors. In my 2008 interview with Dr. James Gordon, an expert in using mind-body medicine to heal depression, he stated that physical exercise is at least as good as antidepressants for helping people who are depressed.
If you’re struggling with depression or depressive symptoms, seek help, from a counselor, a holistic psychiatrist or another natural health practitioner to start the journey toward healing. And, realize that antidepressants carry risks, including increasing the risk of suicide and violence,32 and are not the only available treatment.
In many cases, exercise, sleep and dietary changes can work wonders, especially when combined with nutritional and light therapy, along with energy psychology tools such as the Emotional Freedom Techniques (EFT). Supplements, including magnesium, omega-3 and B vitamins, along with vitamin D, can also be helpful in restoring optimal mental health.
If you’re in the throes of depression, it can be nearly impossible to commit to positive lifestyle changes, so please don’t suffer in silence. Get help from a health partner who can guide you out of crisis mode and into a mindset that allows you to make healthy changes.
Interstitial cystitis (IC) is a chronic bladder condition that may cause scarring and stiffening of the bladder walls. Researchers1 have found that only 10% of those who suffer from IC are men. In the male population, characteristic symptoms include pelvic pain, dysfunction with urination and chronic prostatitis with pain associated with sexual activity. Women who have the condition often have chronic pain in their bladder, irritable bowel syndrome and other issues.
In a population-based study, researchers found the median age of onset was 40 years and up to 50% would experience a spontaneous remission ranging from one month to 80 months. Those with IC were twice as likely to have a history of urinary tract infections.
The researchers found the quality of life in those suffering from IC was lower than those of individuals going through chronic dialysis for renal failure. It's estimated more than 1 million in the U.S. suffer from this condition, most of whom are women. To date, there's only one medication approved by the U.S. Food and Drug Administration to treat IC.2
The drug Elmiron was approved for use in October 1996 as a treatment for pain and discomfort associated with the condition.3 Since it has been the cornerstone of treatment for decades, it's estimated hundreds of thousands have used the drug.
In 2018, Dr. Nieraj Jain from the Emory Eye Center in Atlanta reported six of his patients had developed changes in the central area of the retina called the macula, which had led to reading difficulties and visual changes the patients experienced in dark conditions.4 Six patients underwent genetic testing as part of an inquiry aimed at identifying the reason for the damage, but none was found other than long-term use of Elmiron.
The macula, located in the central area of the retina, is responsible for clear central vision. After a review of the patient's medical history and diagnostic testing, Jain could find nothing explaining the pattern of abnormalities and so raised a warning that long-term use of Elmiron may have damaged his patient’s retinas.5
Subsequently, three ophthalmologists from Kaiser Permanente did a review of 4.3 million patients in northern California and found nearly 25% of those who had been taking Elmiron exhibited signs of eye damage. The researchers determined the damage caused by toxicity from the medication may have been masquerading as other conditions, such as pattern dystrophy or age-related macular degeneration.6
In the 4.3 million patients the team reviewed, they found 140 who had taken an average of 5,000 pills over 15 years. Of those, 91 agreed to an examination and 22 demonstrated clear signs of toxicity. The researchers found the rate of toxicity and damage increased as the dosage the patients took increased.7
Dr. Robin Vora is chair of ophthalmology at Kaiser Permanente and lead researcher of the study. He commented on the outcome of treatment for IC using Elmiron:8
“It’s unfortunate. You have a patient with a chronic condition like interstitial cystitis, for which there is no cure and no effective treatment. They get put on these medications because it’s thought to have few side effects and few risks, and no one thinks about it again. And year after year, the number of pills they’re taking goes up and up.”
If the damage is identified early, researchers are hopeful it may be mitigated when the medication is discontinued.9 Vora recommends those taking the medication who have no symptoms and show no signs of retinal toxicity should be screened annually.10
How the retinal damage is caused by Elmiron is unclear, but Jain’s team suggests a component of the drug may play a role. Researchers from the Cleveland Clinic suggest Elmiron is an antagonist of signaling pathways for fibroblast growth factor.
To date, no research has identified the mechanism triggering the damage. The FDA has not taken any action or issued an alert despite information that the drug is associated with retinal damage in those who are using it.
There is some concern that visual damage may be an unrecognized effect of IC since its presentation is not like any other identified maculopathy. Researchers report that in later stages, toxicity looks like late-stage atrophic age-related macular degeneration, which results in permanent vision loss.
Your bladder is a hollow muscle designed to collect urine excreted from the kidneys before it signals your brain it's time to empty.11 This communication happens through the pelvic nerves and creates an urge to urinate. Unfortunately, those suffering with IC get the signals mixed up and feel the urge to urinate more frequently.
The condition is also called painful bladder syndrome since it triggers recurring bouts of pain. Sufferers may experience the urge to urinate up to 60 times a day, including during the night. Only half of those with the disorder are able to work full time. Those suffering with IC may also experience migraine headaches, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome and allergies.
The exact mechanism for the condition is unknown but biopsies have indicated abnormalities in the bladder wall. Lines of research into the trigger are focused on the inner layer of the bladder wall that may allow toxins to leak through or substances that block the normal growth of the cells lining the bladder.
Others have theorized a viral agent may trigger an infection or an autoimmune disorder may be responsible. Since the trigger is unknown, the diagnosis is made by excluding other similar conditions. Testing and treatment are usually done by a urologist or gynecologist to rule out infections, bladder stones, kidney disease, multiple sclerosis and sexually transmitted diseases, among other disorders.
Management of the condition often starts with conservative measures. The most common medication used has been Elmiron, the only drug approved specifically for the treatment of IC. It can take several months to feel an effect, and the effect may only be modest. Other drugs used include painkillers, tricyclic antidepressants to help relax the bladder and antihistamines to block mast cell release.
In addition to medication, management may also include dietary modification, stress reduction and therapy.12 The IC Network13 recommends identifying the foods that trigger your symptoms and irritate your bladder, as dietary modification is a crucial first step in taking charge of your condition and helping protect your bladder.
It may take up to six months to develop a personalized list of foods you know will trigger your symptoms. However, the IC Network offers a starting list of three types of foods that are:
Some of the most bothersome foods include any type of caffeinated drink, alcohol, citrus, spicy foods and artificial sweeteners. Those that are the least bothersome appear to be most fruit and vegetables, water, milk, meat and eggs.
The Interstitial Cystitis Association14 recommends those who suffer to be proactive and plan ahead. The sooner a flare-up is treated, the faster it can be resolved. They recommend self-help techniques to reduce irritation in the bladder such as learning self-hypnosis, stress reduction techniques and relaxation techniques.
Some flare-ups are triggered by wearing restrictive clothing such as pantyhose, tight jeans or slimming garments. Some people experience relief with simple strategies at home including:
If you believe you may have a urinary tract infection, seek medical attention quickly as an infection can trigger a flare-up and may be challenging to resolve if it isn’t addressed right away. One animal study found melatonin improved symptoms and reduced histological damage in the bladder.15 Another preliminary study with 17 women and 5 men found oral supplementation with quercetin provided significant Improvement.16
In addition to the health conditions listed above, those with IC may also experience pelvic floor dysfunction. Exercises with a physical therapist focus on core strengthening and relaxation, and can help relieve pain since pain tends to tighten pelvic muscles and increases discomfort during urination.17
Reducing stress and muscle tension often helps alleviate pain and discomfort, including in those with IC. Emotional Freedom Techniques (EFT) are rather effective and may be used in private or public without the fear of side effects. In two of my past articles I’ve written about EFT and the techniques you may use to reduce your discomfort:
A new study helps to explain how leptin, a hormone produced by fat tissue, influences your motivation to eat.
The researchers described for the first time a collection of leptin-responsive neurons in the brain's lateral hypothalamic area (LHA). Those LHA neurons feed directly into the mesolimbic dopamine system, which controls the rewarding properties assigned to things.
The study therefore adds to growing evidence that leptin doesn't turn your appetite on and off just by controlling whether you feel hungry or full. It can also make you want food more or less regardless of hunger.
By Ron Rosedale, M.D.
It is amazing how the little twists and turns of researchers can have such a profound impact on what we generally come to realize as “scientific truth.” Let me share a recent fascinating example of how this impacted one of the most powerful hormones in your body.
The Ob mouse is a strain of mouse that has a genetic mutation that makes it obese and unhealthy. It has been used for many years as a model of obesity to do research on, though the reason that it was obese had eluded scientists.
This changed when, in 1994, Jeffrey Friedman discovered that this mouse lacked a previously unknown hormone called leptin, and when it was injected with leptin it became thin, vibrant, and very healthy within weeks. This made headlines around the world, "the cure for obesity found" and pharmaceutical companies started tripping over themselves with trillion dollar signs in their eyes to be the first to genetically manufacture leptin on a large-scale.
This did not last long. When people were tested for leptin, it was found that, unlike the Ob mouse, they did not lack leptin; on the contrary almost all overweight and obese people have excess leptin.
These people were "leptin resistant" and giving extra leptin did little good.
The financial disappointment was extreme and scientists working for pharmaceutical companies said that leptin wasn't important anymore since they could not find a drug to control it, and therefore the industry couldn't make money on it. To make big money in medicine one needs a patent and this generally means remedies which are not commonly or easily available -- that are not natural.
This illustrates two extremely unfortunate principles in modern medicine; only those therapies that will make lots of money (generally for the pharmaceutical industry or hospitals), ever get pursued and then taught to physicians (since most of medical education after medical school takes place by drug reps), and these therapies, almost by definition, will be unnatural.
This inhibition of extremely important knowledge is not only unfortunate, it is deadly, and is exemplified by how few people, including doctors, know anything about leptin, though I would consider it to be the most important chemical in your body that will determine your health and lifespan.
Two Hormones that are Vital for Optimal Health
Each and every one of us is a combination of lives within lives. We are made up of trillions of individual living cells that each must maintain itself. Even more significantly, the cells must communicate and interact with each other to form a republic of cells that we call our individual self.
Our health and life depends on how accurately instructions are conveyed to our cells so that they can act in harmony. It is the communication among the individual cells that will determine our health and our life.
The communication takes place by hormones. Arguably therefore, the most important molecules in your body that ultimately will decide your health and life are hormones.
Many would say that genes and chromosomes are the most important molecules, however once born your genes pretty much just sit there; hormones tell them what to do. Certainly, the most important message that our cells receive is how and what to do with energy, and therefore life cannot take place without that.
The two most important hormones that deliver messages about energy and metabolism are insulin and leptin.
Metabolism can roughly be defined as the chemistry that turns food into life, and therefore insulin and leptin are critical to health and disease. Both insulin and leptin work together to control the quality of your metabolism (and, to a significant extent, the rate of metabolism).
Insulin works mostly at the individual cell level, telling the vast majority of cells whether to burn or store fat or sugar and whether to utilize that energy for maintenance and repair or reproduction. This is extremely important as we shall see, for on an individual cell level turning on maintenance and repair equates to increased longevity, and turning up cellular reproduction can increase your risk of cancer.
Leptin, on the other hand, controls the energy storage and utilization of the entire republic of cells allowing the body to communicate with the brain about how much energy (fat) the republic has stored, and whether it needs more, or should burn some off, and whether it is an advantageous time nutritionally-speaking for the republic --you-- to reproduce or not.
What Exactly is Leptin?
Leptin is a very powerful and influential hormone produced by fat cells that has totally changed the way that science (real science, outside of medicine) looks at fat, nutrition, and metabolism in general.
Prior to leptin's discovery, fat was viewed as strictly an ugly energy storage depot that most everyone was trying to get rid of. After it was discovered that fat produced the hormone leptin (and subsequently it was discovered that fat produced other very significant hormones), fat became an endocrine organ like the ovaries, pancreas and pituitary, influencing the rest of the body and, in particular, the brain.
Leptin, as far as science currently knows, is the most powerful regulator that tells your brain what to do about life's two main biological goals: eating and reproduction. Your fat, by way of leptin, tells your brain whether you should be hungry, eat and make more fat, whether you should reproduce and make babies, or (partly by controlling insulin) whether to "hunker down" and work overtime to maintain and repair yourself.
I believe I could now make a very convincing and scientifically accurate statement that that rather than your brain being in control of the rest of your body, your brain is, in fact, subservient to your fat -- and leptin.
In short, leptin is the way that your fat stores speak to your brain to let your brain know how much energy is available and, very importantly, what to do with it. Therefore, leptin may be "on top of the food chain" in metabolic importance and relevance to disease.
How Leptin Regulates Your Weight
It has been known for many years that fat stores are highly regulated. It appeared that when one tried to lose weight the body would try to gain it back. This commonly results in "yo-yo" dieting and in scientific circles one talks about the "set point" of weight. It has long been theorized that there must be a hormone that determines this.
Science points now to leptin as being that hormone.
In our ancestral history, it was advantageous to store some fat to call upon during times of famine. However, it was equally disadvantageous to be too fat. For most of our evolutionary history, it was necessary to run, to obtain prey and perhaps most importantly, to avoid being prey. If a lion was chasing a group of people it would most likely catch and eliminate from the gene pool the slowest runner and the one who could not make it up the tree -- the fattest one.
Thus, fat storage had to be highly regulated and this is done, as is any regulation, through hormones, the most significant being leptin.
If a person is getting too fat, the extra fat produces more leptin which is supposed to tell the brain that there is too much fat stored, more should not be stored, and the excess should be burned.
Signals are therefore sent to an area of the brain in the hypothalamus (the arcuate nucleus) to stop being hungry, to stop eating, to stop storing fat and to start burning some extra fat off.
Controlling hunger is a major (though not the only) way that leptin controls energy storage. Hunger is a very powerful, ancient, and deep-seated drive that, if stimulated long enough, will make you eat and store more energy. Asking somebody to not eat, to voluntarily restrict calories even though they are hungry, is asking the near impossible. The only way to eat less in the long-term is to not be hungry, and the only way to do this is to control the hormones that regulate hunger, the primary one being leptin.
How Leptin Resistance Leads to Disease
More recently, it has been found that leptin not only changes brain chemistry, but can also "rewire" the very important areas of the brain that control hunger and metabolism. I'm not aware of any other chemical in the body that has been shown to accomplish this "mind bending" event.
This has really caught the attention of the scientific community. Further studies have now shown that leptin, or more correctly the inability of the body to properly hear leptin’s signals, in other words leptin resistance, plays significant if not primary roles in heart disease, obesity, diabetes, osteoporosis, autoimmune diseases, reproductive disorders, and perhaps the rate of aging itself.
It helps to control the brain areas that regulate thyroid levels and the sympathetic nervous system which also has huge impacts on blood pressure, heart disease, diabetes, osteoporosis and aging. Leptin's stimulatory effect on the sympathetic nervous system also helps determine the adrenal stress response including cortisol levels.
Leptin May Be Even More Critical Than Insulin
The importance of insulin in health and disease is becoming well-known. Aside from its obvious role in diabetes, it plays a very significant role in hypertension, cardiovascular disease, and cancer.
I was one of the first to speak publicly to doctors about insulin’s critical role in health well over a decade ago (see the transcribed talk Insulin and its Metabolic Effects) and I am even more convinced now.
However leptin may even supersede insulin in importance, for new research is revealing that in the long run glucose and therefore insulin levels may be largely determined by leptin.
It had been previously believed that the insulin sensitivity of muscle and fat tissues were the most important factor in determining whether one would become diabetic or not. Elegant new studies are showing that the brain and liver are most important in regulating a person’s blood sugar levels especially in type 2 or insulin resistant diabetes.
It should be noted again that leptin plays a vital role in regulating your brain’s hypothalamic activity which in turn regulates much of a person’s "autonomic" functions; those functions that you don't necessarily think about but which determines much of your life (and health) such as body temperature, heart rate, hunger, the stress response, fat burning or storage, reproductive behavior, and newly discovered roles in bone growth and blood sugar levels.
Another very recent study reveals leptin's importance in directly regulating how much sugar that the liver manufactures via gluconeogenesis.
Many chronic diseases are now linked to excess inflammation such as heart disease and diabetes. High leptin levels are very pro-inflammatory, and leptin also helps to mediate the manufacture of other very potent inflammatory chemicals from fat cells that also play a significant role in the progression of heart disease and diabetes. It has long been known that obesity greatly increased risk for many chronic diseases including heart disease and diabetes, but no one really knew why.
Leptin appears to be the missing link.
Could Leptin Also Affect How Fast You Age?
Leptin will not only determine how much fat you have, but also where that fat is put. When you are leptin resistant you put that fat mostly in your belly, your viscera, causing the so-called "apple shape" that is linked to much disease. Some of that fat permeates the liver, impeding the liver's ability to listen to insulin, and further hastening diabetes.
Leptin plays a far more important role in your health than, for instance, cholesterol, yet how many doctors measure leptin levels in their patients, know their own level, even know that it can be easily measured, or even what it would mean?
Leptin appears to play a significant role in obesity, heart disease, osteoporosis, autoimmune diseases, inflammatory diseases and cancer. These are the so-called "chronic diseases of aging".
Could it perhaps affect the rate of aging itself?
The Biology of Aging
Scientists who study the biology of aging are beginning to look at that question. There are two endeavors, two drives that life has been programmed, since its inception, to succeed at and to succumb to. These are to eat and to reproduce.
If every one of our ancestors had not succeeded in eating and reproducing we would not be here, and this paper would be moot. All of your morphological characteristics from your hair to your toenails are designed to help you succeed at those two activities. That is what nature wants us to do. Nature's purpose is not necessarily to have you live a long and healthy life, but to perpetuate the instructions, the genes that tell how to perpetuate life.
Even so-called "paleolithic" diets, though undoubtedly far better than what is generally eaten today, were not necessarily designed by nature to help us live a long and healthy life but, at best, to maximize reproduction. Nature appears to not care much about what happens to us after we have had a sufficient chance to reproduce. That is why we die.
But there are clues as to how to live a long and healthy life. And that brings us once again to fat--and leptin.
It takes energy to make babies; lots of it. Energy was and always will be a coveted commodity. Nature, and evolution, hates wasting it. It makes no sense to try and make babies when it appears that there's not enough energy available to successfully accomplish that goal.
Instead, it seems that virtually all living forms can "switch gears" and direct energy away from reproduction and towards mechanism that will allow it to "hunker down" for the long haul and thus be able to reproduce at a future more nutritionally opportune time. In other words nature will then let you live longer to accomplish its primary directive of reproduction.
It does this by up regulating maintenance and repair genes that increase production of intracellular antioxidant systems, heat shock proteins (that help maintain protein shape), and DNA repair enzymes. This is what happens when you restrict calories (without starvation) in animals, and that has been shown convincingly for 70 years to greatly extend the life span of many dozens of species. Thus, there is a powerful link between reproduction, energy stores, and longevity.
Genetic studies in simple organisms have shown that that link is at least partially mediated by insulin (which in simple organisms also functions as a growth hormone), and that when insulin signals are kept low, indicating scarce energy availability, maximal lifespan can be extended--- a lot; several hundred percent in worms and flies.
Glucose is an ancient fuel used even before there was oxygen in the atmosphere, for life can burn glucose without oxygen; it is an anaerobic fuel. The use of fat as fuel came later, after life in the form of plants soaked the earth in oxygen, for you cannot burn fat without oxygen.
The primary source of energy stores in people by far is fat, as many unfortunately are all too aware of. The primary signal that indicates how much fat is stored is leptin, and it is also leptin that allows for reproduction, or not.
It has long been known that women with very little body fat, such as marathon runners, stop ovulating. There is not enough leptin being produced to permit it. Paradoxically, the first pharmaceutical use of leptin was recently approved to give to skinny women to allow them to reproduce.
Leptin’s Role in Improving Your Metabolism
Leptin also is instrumental in regulating body temperature, partly by controlling the rate of metabolism via its regulation of the thyroid.
Metabolic rate and temperature has long been connected with longevity. Almost all mechanisms that extend lifespan in many different organisms result in lower temperature. Flowers are refrigerated at the florist to extend their lifespan. Restricting calories in animals also results in lower temperature, reduced thyroid levels, and longer life.
It should be noted that reduced thyroid levels in this case are not synonymous with hypothyroidism. Here, the body is choosing to lower thyroid hormones because the increased efficiency of energy use and hormonal signaling (including perhaps thyroid) is allowing this to happen.
Anything will dissolve faster in hot water than cold water. Extra heat will dissolve, disrupt and disorganize. This is not what I try to do to make someone healthy. It is commonly advised to "increase metabolism" and increase "thermogenesis" for health and weight loss.
Yet how many of you would put a brand of gasoline in your car that advertised that it would make your engine run hotter? What would that do to the life of your car? It is not an increase in metabolism that I am after; it is improved metabolic quality.
That will be determined at the quality of your leptin signaling.
If it is poor, if you are insulin and leptin resistant, your metabolism is unhealthy and high in what I call "metabolic friction". If you then increase its rate you will likely accelerate your demise. To increase the quality of your metabolism you must be able to properly listen to insulin and especially to leptin.
If your fasting blood serum level of leptin is elevated you are likely leptin resistant and you will not be healthy unless you correct it.
How Do You Become Leptin Resistant?
This is the subject of much research. I believe people become leptin-resistant by the same general mechanism that people become insulin-resistant; by overexposure to high levels of the hormone.
High blood glucose levels cause repeated surges in insulin, and this causes one's cells to become "insulin-resistant" which leads to further high levels of insulin and diabetes. It is much the same as being in a smelly room for a period of time. Soon, you stop being able to smell it, because the signal no longer gets through.
I believe the same happens with leptin. It has been shown that as sugar gets metabolized in fat cells, fat releases surges in leptin, and I believe that those surges result in leptin-resistance just as it results in insulin-resistance.
The only known way to reestablish proper leptin (and insulin) signaling is to prevent those surges, and the only known way to do that is via diet and supplements.
As such, these can have a more profound effect on your health than any other known modality of medical treatment.
When leptin signaling is restored, your brain can finally hear the message that perhaps should have been delivered decades ago; high leptin levels can now scream to your brain that you have too much fat and that you better start burning some off for your life is in danger.
Your brain will finally allow you access into your pantry that you have been storing your fat in. Your cells will be fed the food from that fat and they will be satisfied. They will not know whether that food came from your belly fat or from your mouth; nor will they care. They will be receiving energy that they need and will not have to ask for more. You will not be hungry.
This also makes counting calories irrelevant, for the calories that you put into your mouth today are not necessarily what your cells will be eating; that will be determined primarily by leptin. Whether or not you put food into your mouth, your cells will be eating, and if they cannot eat fat they must eat sugar.
Since little sugar is stored, that sugar will be had by making you crave it, or by turning the protein in your muscle and bone into sugar. This contributes in a major way to weakness and osteoporosis. Whether or not this lean tissue wasting happens is determined by your capacity, or incapacity, to burn fat, and that is determined by your ability to listen to leptin.
A strategic diet that emphasizes good fats and avoids blood sugar spikes coupled with targeted supplements (as recommended in my Rosedale Diet and Dr. Mercola’s Take Control of Your Health), will enhance insulin and leptin sensitivity so that you can once again hear their music, allowing your life to be the symphony it was meant to be.
