Beneficial Bacteria for Humans: Probiotics, Prebiotics and Postbiotics

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Beneficial Bacteria for Humans: Probiotics, Prebiotics and Postbiotics

Probiotics are among the hottest supplements of 2019 and with good reason. The positive role of these “good” bacteria are being revealed in everything from digestive health to brain support on an almost-daily basis.

Learn more about probiotics, prebiotics and postbiotics below, or listen to the podcast on in which Life Extension’s own Michael A. Smith, MD, discusses the latest information concerning probiotics with nutrition expert Crystal Gossard, DCN, CNS, LDN.

While most of us are familiar with antibiotics, not everyone knows exactly what probiotics are. While antibiotics reduce or stop the growth of bacteria, probiotics are bacteria. The difference between these bacteria and those we seek to combat with antibiotics is that probiotic microorganisms are beneficial to the body, and therefore desirable, while those we want to treat with antibiotics are, of course, potentially harmful.

What are probiotics good for?

Probiotics colonize the intestinal tract and support gastrointestinal health, including digestion. We are learning more all the time about how they can benefit not only the GI tract, but the entire body. In fact, there are an estimated 10 times more microbial cells in the human body than human cells.1 Many of these microorganisms are the beneficial bacteria known as probiotics.

Common Probiotics and Probiotic Strains

Probiotic bacteria are classified by genus, species and strain. Two common genera are Lactobacillus and Bifidobacterium. Other genera include Escherichia, Enterococcus, Bacillus, Propionibacterium, Streptococcus, Pediococcus, Leuconostoc and Saccharomyces. Common Lactobacillus species are acidophilus, bulgaricus, casei, fermentum, plantarum and rhamnosus, and better-known Bifidobacterium include animalis, bifidum, breve, infantis, lactis and longum. Following these species names may be a number or letter designating the strain, as in Lactobacillus acidophilus NCFM.

Best Foods for Gut Health: Foods High in Probiotics

Yogurt is the most well-known food that contains one or more probiotic cultures. Other foods that contain probiotics include fermented products such as kimchi, miso, sauerkraut, kombucha, kefir, buttermilk, some cheeses and sourdough. Probiotics are also available in supplement form.

Probiotics Supplements: Multiple Strains

Probiotics in supplemental form are capsules, liquids or lozenges that contain concentrated amounts of probiotic bacteria. Popular probiotic species are Lactobacillus acidophilus, Lactobacillus rhamnosus, Lactobacillus bulgaricus, Bifidobacterium infantis and Bifidobacterium bifidum, among others. Many supplements contain several strains to support a specific area of concern or general well-being.

Why take probiotics?

Probiotics help maintain healthy intestinal flora by limiting the overgrowth of potentially harmful bacteria. The balance of bacteria that live in our intestines is important for digestive and immune health.2 Probiotic bacteria may also help control the overgrowth of fungi such as Candida albicans, not only in the intestines, but in the mouth and other areas.3

Probiotics have been used around the world for many years in various forms. The legendary longevity benefits attributed to probiotic foods such as kefir might have a basis in their recently revealed health properties. While not everyone likes yogurt or sauerkraut, and kimchi may be hard to find, consuming a probiotic capsule is an easy way to encourage healthy microflora.

How do probiotics affect the brain?

The beneficial effect on mental states that may be associated with probiotics is facilitated by signaling between the digestive tract and the brain.4 The gut and braincommunicate through the vagus nerve, endocrine signaling mediators and the immune system.

It has been observed that Alzheimer’s disease and Parkinson’s disease patients have a high incidence of gastrointestinal disorders.5,6 Unfavorable alterations in gut microflora may result in greater permeability of the gut barrier, potentially leading to immune activation and systemic inflammation. This can impair the function of the blood-brain barrier, thereby causing neuroinflammation and neurodegeneration.7 Therefore, management of intestinal flora may help support brain health.

An article published in 2019 – “Man and the microbiome: a new theory of everything?” – observes that the gut microbiome has been implicated in a variety of psychological disorders. “Preclinical studies have provided us with key insights into the mechanisms by which the microbiome influences bidirectional gut-brain communication,” the authors write. “The complex and widespread influence of the microbiome on many physiological and psychological processes has generated a keen interest in its therapeutic potential for depression, anxiety, autism, and other psychiatric disorders. It has been shown that the microbiome composition of people suffering with such conditions differs significantly from that of healthy controls, and although the area is in its infancy, interventional studies that alter a person’s microbiome through the use of probiotics, prebiotics, or dietary change can alleviate psychopathological symptoms.”8

The Difference Between Prebiotics and Probiotics

Prebiotics act as food for probiotic bacteria. Inulin from chicory and fructo-oligosaccharides (FOS) from inulin are common prebiotic supplements that nourish probiotics. Other prebiotics include beans, legumes, starchy fruits, cereals, onions and other vegetables, as well as other foods such as milk and fungi.9 Polyphenols such as resveratrol and anthocyanins also have prebiotic properties.9

What are postbiotics?

Postbiotics have been defined as “those molecules released by bacteria and other microorganisms that, when administered in adequate amounts, confer health benefits to the host.”10 It is the opinion of the author of this definition that greater benefit may be derived from the ferment of fermented foods than the bacteria present in the foods: “The many nutrients the bacteria make, what I call the postbiotics, while fermenting the foods, are what are beneficial to the GI and the immune system.”10

Postbiotics are nonliving compounds that have a long shelf life.Among the hundreds of postbiotics are peptides and the short-chain fatty acids acetate, butyrate and propionate.

What are Phages and How Do They Work?

“Phages” is a short way of saying “bacteriophages,” which describes submicroscopic packages of DNA or RNA enclosed in a protein envelope that target bacteria. Certain bacteriophages selectively target specific undesirable bacteria while leaving beneficial bacteria undisturbed.

Bacteriophages were discovered over 100 years ago and are generating renewed interest in the face of antibiotic resistance.11

Bacteriophage Probiotic: What is phage therapy?

Phage therapy involves the use of bacteriophages in the treatment of bacterial infections. Phages can also be used preventively. Combining phages with probiotics may reduce the growth of undesirable bacteria, allowing the beneficial probiotic bacteria to thrive.

About Live Foreverish: Join Dr. Mike as he sits down with some of today’s leading medical, health and wellness experts to discuss a variety of health-related topics. From whole-body health to anti-aging and disease prevention, you’ll get the latest information and advice to help you live your life to the fullest. If you like what you hear, please take a moment to give Live Foreverish a 5-star rating on iTunes!


  1. Turnbaugh PJ et al. Nature. 2007 Oct 18;449(7164):804-10.
  2. Alarcón P et al. Rev Med Chil. 2016 Jul;144(7):910-6.
  3. Rossoni RD et al. Biofouling. 2018 Feb;34(2):212-225.
  4. Breit S et al. Front Psychiatry. 2018 Mar 13;9:44.
  5. Westfall S et al. Cell Mol Life Sci. 2017 Oct;74(20):3769-3787.
  6. Sarkar S et al. J Neuroimmunol. 2019 Mar 15;328:98-104.
  7. Kowalski K et al. J Neurogastroenterol Motil. 2019 Jan 31;25(1):48-60.
  8. Butler MI et al. Annu Rev Clin Psychol. 2019 Feb 20.
  9. Reynés B et al. Front Physiol. 2019 Jan 10;9:1908.
  10. Maguire M et al. Rev Neurosci. 2019 Jan 28;30(2):179-201.
  11. Kortright KE et al. Cell Host Microbe. 2019 Feb 13;25(2):219-232.

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Live Foreverish Podcast: New Treatments for Chronic Pain Relief

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Live Foreverish Podcast: New Treatments for Chronic Pain Relief

New Treatments for Chronic Pain Relief

The latest research shows that natural medicine could be the best place to look for new chronic pain treatments. Researchers recently discovered an intrinsic fatty acid, called PEA (Palmitoylethanolamide), that inhibits peripheral nerve inflammation—theorized as the first step in developing chronic pain.

Additionally, a little-known plant extract called honokiol improves GABA signaling in the brain, thus restoring a normalized perception of pain—an important step for chronic pain relief.

The newest approach to finding relief might include supplementing with PEA and honokiol. Life Extension®’s Michael A. Smith, MD, and Crystal Gossard, DCN, CNS, LDN, discuss chronic pain and readily available solutions that don’t involve opioids in this episode of Live Foreverish.

What is Chronic Pain?

Chronic Pain Definition

Did you know that chronic pain is not only long-term, day-in-and-day-out pain, but a diagnosis in its own right?

Chronic pain is defined as persistent or recurrent pain lasting longer than 3 months.1 While acute pain is the temporary pain that is the result of numerous possible occurrences or conditions, chronic pain is something that many people live with 24 hours a day, often for years. It is a condition that involves more than the site of the initial insult to the body and includes changes that occur in the spinal cord and the brain.

Chronic pain is now recognized as a diagnosis that is separate from any disease or condition that may have initiated it. As an article published recently in the journal Postgraduate Medicine noted, “Evidence supports the redefinition of chronic pain as a distinct disease entity, not simply a symptom of injury or illness.”2

According to a recent review, “If one views chronic pain as a single disease entity, then it is the most common and costly medical condition.”3

Chronic pain symptoms

In addition to persistent, significant pain, people suffering from chronic pain unsurprisingly endure other symptoms, including a significant amount of stress which, in turn, can aggravate their pain.4 Depression, anxiety, insomnia, physical disability and even cognitive changes can also be experienced by those suffering from chronic pain.

Current chronic pain treatment

Chronic pain is generally treated with prescription and nonprescription pain-relieving drugs. Nonprescription drugs include acetaminophen (Tylenol) and nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, ibuprofen (Advil) and naproxen (Aleve). NSAIDs also include the prescription drugs celecoxib (Celebrex), diclofenac (Voltaren), indomethacin and others. While prescription opioid derivatives—including hydrocodone, fentanyl, codeine, morphine, and oxycontin—are considered good at relieving pain, some people become addicted in a matter of weeks of regular use and experience other significant side effects.

Local anesthetic injections that can be administered by a physician are sometimes an option. There are also pain-relieving patches, balms, lotions and ointments that can be applied topically.

Natural therapies for chronic pain include acupuncture, spinal adjustments, exercise, physical therapy, meditation, massage and specific plant compounds.5

PEA and Honokiol–Exciting New Options for Pain Relief

How does PEA work?

Palmitoylethanolamide, which (fortunately) is referred to by its acronym PEA, is a fatty acid produced in the human body that also occurs in small amounts in egg yolk, milk, soy and other foods.6 Available clinical data support the ability of PEA to relieve discomfort.7 The compound targets the mast cells activated peripherally during the initial insult to the body that is the first step in the development of chronic pain, thereby reducing the release of inflammatory mediators. PEA’s action against mast-cell driven localized inflammation is what makes it different from other compounds—natural and otherwise—that have an anti-inflammatory action.6

PEA also targets the nuclear receptor peroxisome proliferator-activated receptor-alpha (PPAR-alpha) to support a healthy level of inflammation. According to a recent review, “Synergistic interactions among several mechanisms often seem necessary so that PEA can produce its important therapeutic effects, both in the central and the peripheral nervous system.”6

Human studies have revealed benefits for the use of PEA for sciatic nerve pain, carpal tunnel syndrome, temporomandibular joint (TMJ) syndrome and migraine.8- 11 Doses used in these trials range from 300 milligrams to 1,200 milligrams.

What is honokiol?

Honokiol is a compound derived from the magnolia tree. Honokiol targets resistance to the inhibitory gamma-aminobutyric acid (GABA) in brain—a phenomenon that occurs as the final stage in the development of chronic pain syndrome. GABA slows down the rate at which neurons fire, which results in a calming effect.12

“The results of anatomical, biochemical, molecular and pharmacological studies support the notion that generalized activation of GABA receptor systems dampens the response to painful stimuli,” write S. J. Enaa and K. E. McCarson in Advances in Pharmacology. “The data leave little doubt that, under certain circumstances, stimulation of neuroanatomically discreet GABA receptor sites could be of benefit in the management of pain.”13

Targeting the beginning and the end of the development of chronic pain is one way to break the pain cycle. Unlike NSAIDs, PEA and honokiol are safe on the stomach, and unlike opioid drugs, they’re nonaddictive.

Although chronic pain has frustrated patients and physicians alike, there are treatment options that don’t involve the use of dangerous and addictive drugs. Do you or someone you care about suffer from chronic pain?

About Live Foreverish: Join Dr. Mike as he sits down with some of today’s leading medical, health and wellness experts to discuss a variety of health-related topics. From whole-body health to anti-aging and disease prevention, you’ll get the latest information and advice to help you live your life to the fullest. If you like what you hear, please take a moment to give Live Foreverish a 5-star rating on iTunes!


  1. Nicholas M et al. Pain. 2019 Jan;160(1):28-37.
  2. Clauw DJ et al. Postgrad Med. 2019 Jan 31:1-14.
  3. Nicol AL et al. Anesth Analg. 2017 Nov;125(5):1682-1703.
  4. Crofford LJ. Trans Am Clin Climatol Assoc. 2015;126:167-83.
  5. Wylde V et al. Br J Surg. 2017 Sep;104(10):1293-1306.
  6. Petrosino S et al. Br J Pharmacol. 2017 Jun;174(11):1349-1365.
  7. Artukoglu BB et al. Pain Physician. 2017 Jul;20(5):353-362.
  8. Guida G et al. Dolor. 2010;25(1):35–42.
  9. Assini A et al. Eur J Neurol. 2010;17(S3):295.
  10. Marini I et al. J Orofac Pain. 2012 Spring;26(2):99-104.
  11. Chirchiglia D et al. Front Neurol. 2018 Aug 17;9:674.
  12. Ai J et al. Pharmacology. 2001 Jul;63(1):34-41.
  13. Enna SJ et al. Adv Pharmacol. 2006;54:1-27.

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Are We Getting Enough Nutrients from Food?

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Are We Getting Enough Nutrients from Food?
Holli Ryan, RD, LD/N

Do the foods we eat provide us with optimal nutrition?

In other words, are we getting enough
nutrients, such as vitamins and minerals, from our food? Even if you eat a varied diet, including the recommended amounts of fruits and vegetables, the answer might still be no. The reason is that factors such as climate change and soil quality play a role in the nutrient profile of a given food.

Is our soil depleted of nutrients?

Intensive farming practices have led to a depletion of key nutrients such as magnesium, calcium and vitamin C in soil.1,2 The decreased mineral content in the soil could make it challenging to obtain optimal levels from food sources alone, and this may have a significant impact on human health.

While fertilization techniques developed as part of the Green Revolution have increased the production of food since the late 1960s, one consequence has been a reduction in the amounts of minerals and vitamins in our food. The result? More food, fewer nutrients. Since the revolution, magnesium levels in wheat, for example, have declined by an average of 19.6%.On the plus side, the introduction of GM crops has played a role in reducing topsoil damage, which is beneficial to the environment.

Does climate change affect our food supply?

The rising levels of carbon dioxide in the atmosphere that accompany climate change are affecting the nutrient status of our food.4 The analogy put forth by the blog article from Scientific American entitled “Vanishing Nutrients” is that too much carbon dioxide is as unhealthy for plants as too many carbohydrates are for humans.5 Intriguingly, the article goes on to explain: “Extra carbon dioxide acts like empty calories or ‘junk food’ for the plants, which gorge themselves on it to grow bigger and faster, consequently getting larger but less nutrient-packed. Just like America’s obesity epidemic, which is partially due to people’s increased access to an abundance of calorie-rich but nutrient-poor food, more is not always better.”

Related Article: 5 Foods You Aren’t Eating Enough

I asked Nall Moonilall, a Ph.D student at the Ohio State University Carbon Management and Sequestration Center, for his insight on this topic. He recommends we protect the soil, keep it covered, maintain a healthy and active soil microbial community and add more organic matter. “Sequestering more carbon in soil will help to build the soil and improve overall soil health. Adding organic matter, reducing tillage, adding manures, and promoting diversified cropping systems are all management practices that assist to sequester more carbon and improve soil quality. This in turn will enhance better nutrient cycling in the soil.”

Sequestering carbon (capturing and storing atmospheric carbon dioxide, which is converted to a stable, solid form in soil) is one method of reducing the amount of carbon dioxide in the atmosphere with the goal of reducing global climate change—and the added benefits of decreasing nutrient loss and improving soil and water quality.6

Is organic produce healthier (more nutritious) than conventional produce?

We’ve seen how farming practices have been shown to have an influence on the nutrient content of our food, and the use of pesticides in conventional growing methods is yet another scenario that has been shown to have a negative impact.7 I find the effect on the antioxidant status of plants particularly interesting.8 First off, the fact that plants produce antioxidants to protect themselves from the environment, and then we, in turn, inherit those same protective benefits by eating the plant, is amazing. Knowing this, the explanation as to why there are more antioxidants in organic produce makes perfect sense: Organic crops need to fend for themselves more than conventional crops, which have strong, synthetic pesticides to help defend them. Organic crops, therefore, are under a higher level of stress and have to produce more antioxidants to deter pests. However, certain pesticides (typically non-man-made) are used on organic crops, especially for large-scale crop production. So how do we get the most nutrients from produce? I suggest buying from your local organic farmer and growing some of your own food.

About the author: Holli Ryan, RD, LD/N is a Social Media Content Specialist at Life Extension®. She is a Registered and Licensed Dietitian Nutritionist residing in the South Florida area. Holli believes that quality dietary supplements are an essential tool that have a variety of applications, from maintaining good health to managing chronic disease.


  1. Rosanoff A. Changing crop magnesium concentrations: impact on human health. Plant and Soil. 2012;368(1-2):139-153.
  2. Davis DR, Epp MD, Riordan HD. Changes in USDA Food Composition Data for 43 Garden Crops, 1950 to 1999. Journal of the American College of Nutrition. 2004;23(6):669-682.
  3. Guo W, Nazim H, Liang Z, et al. Magnesium deficiency in plants: An urgent problem. The Crop Journal. 2016;4(2):83-91.
  4. Zhu C, Kobayashi K, Loladze I, et al. Carbon dioxide (Co2) levels this century will alter the protein, micronutrients, and vitamin content of rice grains with potential health consequences for the poorest rice-dependent countries. Science Advances. 2018;4(5): eaaq1012.
  6. Lal R, Negassa W, Lorenz K. Carbon sequestration in soil. Current Opinion in Environmental Sustainability. 2015;15:79-86.
  8. Barański M, Srednicka-Tober D, Volakakis N, et al. Higher antioxidant and lower cadmium concentrations and lower incidence of pesticide residues in organically grown crops: a systematic literature review and meta-analyses. British Journal of Nutrition. 2014;112(5):794-811.

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Subclinical Hypothyroid: Underdiagnosed Thyroid Condition

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Subclinical Hypothyroid: Underdiagnosed Thyroid Condition

Tired? Bloated? Dry skin and hair? Constipated? Many people write off these symptoms as part of growing older. But these common conditions may not be due to aging. Those who suffer from them could have a condition that even their physician may fail to identify: subclinical hypothyroidism.

Learn more about thyroid health below, or listen to the podcast on in which Life Extension’s own Michael A. Smith, MD, discusses the latest information.

What is subclinical hypothyroidism?

The difference between hypothyroidism and subclinical hypothyroidism

Many of us know about hypothyroidism (low thyroid hormone levels), but what is subclinical hypothyroidism? Subclinical hypothyroidism has been defined by American Thyroid Association (ATA)/American Academy of Clinical Endocrinology (AACE) guidelines as the presence of a serum thyroid stimulating hormone (TSH) above the upper reference limit in combination with normal free thyroxine (T4). They note that “This designation is only applicable when thyroid function has been stable for weeks or more, the hypothalamic-pituitary-thyroid axis is normal, and there is no recent or ongoing severe illness.”1

“Sub,” when used as a prefix, means “under” or “below,” and “subclinical” refers to a health condition that may not be overtly apparent and can be underdiagnosed according to standard assessments like bloodwork. Individuals with subclinical hypothyroidism are often asymptomatic, however they may experience the non-specific complaints associated with overt hypothyroidism. Symptoms could include fatigue, weakness, weight gain, cold intolerance and constipation. The condition often precedes the development of overt hypothyroidism.2

If thyroid problems are suspected, clinicians will often test only TSH levels. If TSH levels are outside the normal reference range, T4 levels may then be tested as well. Individuals with high TSH levels and normal T4 levels may have subclinical hypothyroidism.

Thyroid stimulating hormone normally rises in response to a decline in thyroid hormones—increasing thyroid hormone levels should therefore decrease TSH levels. According to the American Thyroid Association, a “normal” TSH range is between 0.4-0.5 mU/L on the lower end and 4-5.5 mU/L on the upper end.3

What are subclinical hypothyroidism treatment guidelines?

The European Thyroid Association (ETA) Guideline for the management of subclinical hypothyroidism recommends the drug levothyroxine (L-thyroxine), the synthetic form of T4, for patients younger than 60 to 70 years with TSH levels of greater than 10 mU/L, even in the absence of symptoms. For patients in this age group with TSH levels of less than 10 mU/L who have symptoms of hypothyroidism, they suggest a trial of levothyroxine, followed by a review of one’s response three to four months after a normal TSH level is attained. Among those who are older than 80-85 with elevated serum TSH levels of 10 mU/L or less, the ETA recommends generally avoiding hormonal therapy, but if the decision is to treat the patient, they recommend daily levothyroxine supplementation with a TSH recheck after two months.4

The hormone T4 normally converts to T3, another essential thyroid hormone. In theory, supplementing with T4 should be all that is needed. However, it is possible that not everyone efficiently converts T4 to T3. Individuals using levothyroxine who continue to experience symptoms of hypothyroidism when TSH levels have normalized may wish to have their T3 evaluated. In addition to TSH and T4, a complete thyroid panel will also measure free T4, free tri-iodothyronine (T3), reverse T3, thyroglobulin antibody (ATA) and thyroid peroxidase antibody (TPO).

If one has low T3 levels, the drug Cytomel, which is synthetic T3, may be prescribed in addition to levothyroxine (T4). It is not yet clear whether combination therapy is more effective than levothyroxine monotherapy, however those who do not respond well to monotherapy may consider combination treatment under the guidance of an experienced clinician.5 An alternative is treatment with Armor Thyroid, NP Thyroid or Naturethroid, which contain desiccated bovine thyroid gland tissue that naturally contains T3 as well as T4.

Is subclinical hypothyroidism dangerous?

Low-normal thyroid function may increase total and low-density lipoprotein (LDL) cholesterol and triglycerides and may be associated with metabolic syndrome, insulin resistance and chronic kidney disease.6

Can subclinical hypothyroidism be reversed?

Nutrients that support thyroid function

With the correct dosage of thyroid hormone replacement and periodic blood testing to evaluate the efficacy of the dosage one has been prescribed, subclinical hypothyroidism can be normalized.

There are also several nutrients that support thyroid function. Iodine is the first that comes to mind, due to its necessity for the synthesis of the body’s thyroid hormones. Other minerals that are supportive of thyroid function are selenium and zinc, which are important for the conversion of T4 to T3.7,8 Preclinical studies suggest that the herbCommiphora mukul (guggul) may also be helpful for this purpose.9

Another herb that may help support the thyroid is ginseng. A study of patients with congestive heart failure found an increase in T3 and T4 levels (which, prior to treatment, were lower than those of normal control patients) among participants who received ginseng for two weeks.10

A small study involving supplementation with the ayurvedic herb ashwagandha (Withania somnifera) resulted in increases in T4 after 8 weeks among all those who received the herb and even normalized subclinical hypothyroidism in one patient, while most of those who received a placebo experienced a decline in T4. These initially promising findings suggest a potential use for ashwagandha in subclinical hypothyroidism.11

The Bottom Line

A study involving a sample of 13,344 participants in the National Health and Nutrition Examination Survey III (NHANES III) who were representive of the geographic and ethnic distribution of the U.S. population revealed subclinical hypothyroidism among 4.3% of the subjects.12 Other estimates of the prevalence of subclinical hypothyroidism are higher, and older women are particularly at risk.13

If you are suffering from some of the symptoms of hypothyroidism, it would be well worth your while to rule out this frequently undetected condition, not only to feel better, but to help protect your future health.

About Live Foreverish: Join Dr. Mike as he sits down with some of today’s leading medical, health and wellness experts to discuss a variety of health-related topics. From whole-body health to anti-aging and disease prevention, you’ll get the latest information and advice to help you live your life to the fullest. If you like what you hear, please take a moment to give Live Foreverish a 5-star rating on iTunes!


  1. Garber JR et al. Endocr Pract. 2012 Nov-Dec;18(6):988-1028.
  2. Baumgartner C et al. Swiss Med Wkly. 2014 Dec 23;144:w14058.
  3. Woodmansee WW. Clinical Thyroidology for the Public. 2018 Feb;11(2):3-4
  4. Pearce SHS et al. Eur Thyroid J. 2013 Dec; 2(4): 215–228.
  5. Dayan C and Panicker V. Thyroid Res. 2018 Jan 17;11:1.
  6. van Tienhoven-Wind LJ et al. Eur J Clin Invest. 2015 May;45(5):494-503.
  7. Kawai M. Pediatr Endocrinol Rev. 2019 Mar;16(3):307-310.
  8. Nishiyama S et al. J Am Coll Nutr. 1994 Feb;13(1):62-7.
  9. Panda S et al. Phytother Res. 2005 Jan;19(1):78-80.
  10. Dai X et al. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1999 Apr;19(4):209-11.
  11. Gannon JM et al. J Ayurveda Integr Med. 2014 Oct-Dec;5(4):241-5.
  12. Hollowell JG et al. J Clin Endocrinol Metab. 87:489–499.
  13. Wilson GR et al. Am Fam Physician. 2005 Oct 15;72(8):1517-24.

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Small Molecule Screening for Longevity Effects in Nematode Worms

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A very large fraction of the research aimed at the production of interventions to slow aging involves some form of screening small molecule compounds for potential effects. There are huge stock libraries of these things, and many well established approaches to carrying out such screening processes. While new ventures are using machine learning to try to make this process far more efficient than is presently the case, after the fashion of In Silico Medicine, I’d say that the future will be a matter of gene therapy making small molecules obsolete. Gene therapy offers the possibility of precise alteration of the gene expression of a rationally chosen target, rather than the uncertainty, serendipity, and off-target effects inherent in small molecule development.

Still, much of the community, particularly the business community, will remain firmly tied to small molecule development programs for the foreseeable future. Researchers will continue to innovate when it comes to novel ways to run such programs. The example here makes use of nematode worms as the screening system: pick a set of compounds, see what they do to worm longevity, then investigate the biochemistry of the successes to understand whether or not they work in the expected fashion, and whether or not the mechanism might be applicable to mammals.

It is worth noting that most such discoveries work via alterations of stress response systems or other aspects of metabolism that do not produce large gains in life span in long-lived species. A doubling or more of nematode life span has been achieved in a variety of ways, but none of those are based on underlying mechanisms that have anywhere near the same effects when triggered in mammals. We need to look elsewhere to achieve that outcome, meaning work on deliberative repair of the underlying causes of aging, rather than adjustment of metabolism to modestly slow aging.

Discovery of life-extension pathway in worms demonstrates new way to study aging

Lifespan studies using C. elegans worms typically involve the deletion or silencing of a particular gene in the embryonic stage of life to see if that extends the average lifespan of affected animals. Researchers took a different approach, using small-molecule compounds to disrupt enzyme-related pathways in adult worms, in the hope that this would uncover pathways that regulate lifespan. The team used a library of about 100 such compounds, all known to inhibit enzymes called serine hydrolases in mammals. “Metabolic processes are very important in determining the rate of aging and lifespan, and serine hydrolases are major metabolic enzymes, so we thought there was a good chance we’d find an important aging-related enzyme this way.”

After finding ways to get the compounds through the tough outer skin of the worms, the researchers tested them on worms that were 1 day into adulthood, and found that some of the compounds extended average worm lifespan by at least 15 percent. One, a carbamate compound called JZL184, extended worm lifespan by 45 percent at the optimal dose. More than half the worms treated with JZL184 were still alive and apparently healthy at 30 days, a time when virtually all untreated worms were dead of old age. JZL184 was originally developed as an inhibitor of the mammalian enzyme monoacylglycerol lipase (MAGL), whose normal job includes the breakdown of a molecule called 2-AG. The latter is an important neurotransmitter and is known as an endocannabinoid because it activates one of the receptors hit by the main psychoactive component in cannabis.

Curiously however, a corresponding MAGL enzyme does not exist in C. elegans worms, so JZL184’s target in these animals was a mystery. Researchers found, though, that one of the main target enzymes for JZL184 in worms was fatty acid amide hydrolase 4 (FAAH-4). Although FAAH-4 and MAGL are not related in terms of their amino-acid sequences or 3-D folds, further experiments revealed, surprisingly, that FAAH-4 in worms does what MAGL does in humans and other mammals: it breaks down 2-AG. 2-AG has been linked to aging in mammals; one recent study found evidence that its levels fall in the brains of aging mice, likely due to greater MAGL activity. The results suggest, then, that studying the FAAH-4/2-AG pathway in worms could one day yield lifespan-extending strategies for humans.

Pharmacological convergence reveals a lipid pathway that regulates C. elegans lifespan

Phenotypic screening has identified small-molecule modulators of aging, but the mechanism of compound action often remains opaque due to the complexities of mapping protein targets in whole organisms. Here, we combine a library of covalent inhibitors with activity-based protein profiling to coordinately discover bioactive compounds and protein targets that extend lifespan in Caenorhabditis elegans. We identify JZL184 – an inhibitor of the mammalian endocannabinoid (eCB) hydrolase monoacylglycerol lipase (MAGL or MGLL) – as a potent inducer of longevity, a result that was initially perplexing as C. elegans does not possess an MAGL ortholog.

We instead identify FAAH-4 as a principal target of JZL184 and show that this enzyme, despite lacking homology with MAGL, performs the equivalent metabolic function of degrading eCB-related monoacylglycerides in C. elegans. Small-molecule phenotypic screening thus illuminates pure pharmacological connections marking convergent metabolic functions in distantly related organisms, implicating the FAAH-4/monoacylglyceride pathway as a regulator of lifespan in C. elegans.

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Will Raw Milk Save Dairy Farmers?

Very best Dietary supplements to Support Nitric Oxide Health

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As corporations continue to take control of the food supply, small family farms are giving way to concentrated animal feeding operations (CAFOs) mass producing a surplus of poor-quality food. Conventional milk is a prime example. Milk surpluses have led the price of milk to plummet.

In Wisconsin, farmers are getting nearly 40 percent less for their milk than they were in 2014. Nearly 700 dairy farms closed in the state in 2018, most of them small operations.1

As CAFOs became the norm for dairy farms (even in idyllic-seeming dairy states like Vermont), farmers trying to survive were forced to grow their herds and increase milk production using artificial (drug- and hormone-based) methods, among others (like feeding cows an unnatural amount of grain-based food, 24-hour confinement and increased numbers of milkings per day).

Such was the case for Pennsylvania dairy farmer Edwin Shank, who increased his herd size to 350 cows, used growth hormones and milked cows three times a day — only to face financial ruin as milk prices dropped in the 2000s.

Shank’s story has a happy ending, though, as he is one of a growing number of farmers who’ve been able to not only climb their way out of a failing industry, but also thrive by switching over to a profitable niche market: raw milk.2

Raw Milk Farmers Thrive as Others Shut Down

Many consumers seeking out raw milk do so for health purposes or simply because they love the taste, but raw milk has another advantage in that it’s helping small farmers to thrive. As Civil Eats reported, Shank was in the process of transitioning his dairy to organic when he realized he could sell organic raw milk for nearly 10 times the price he’d been getting before.

Judith McGeary, an attorney and board member with the Farm-to-Consumer Legal Defense Fund, told Civil Eats, “Dairy is an incredibly consolidated system. The farmer has no bargaining power … Raw milk provides this polar opposite; you have this product in high demand by consumers who value it, and all that profit goes to the farmer.”3

Shank’s farm, The Family Cow, is now the largest raw-milk producer in Pennsylvania, taking advantage of increasing interest in this fresh, wholesome food. Likewise, Charlotte Smith, a farmer in Oregon, is able to stay in business by milking just three cows, the number the state law allows for raw milk farmers.

“I milk three cows and my neighbor who milks 300 cows could probably make as much money as me if he sold all his cows and milked three,” she told Civil Eats.4 Meanwhile, the price of conventional milk has gone so low that an average-sized dairy farm in Vermont (about 125 cows) may operate at a loss of $100,000 a year.5

But for Organic Pastures, the largest raw milk dairy in California, sales grew 18 percent from January 2018 to January 2019. Likewise, as conventional milk farmers are shutting down, licenses for raw milk dairies climbed from six in 2006 in Washington state to 32 in 2019. And in New York, permits for on-the-farm sales of raw milk increased from 12 to 37 over the last several years.6

CAFOs Destroy Rural Communities

Across the U.S. Midwest, small farms that once raised a mix of crops and livestock over the course of generations have been disappearing, replaced by agribusiness giants growing monocrops of corn and soy and raising thousands of chickens and pigs in inhumane CAFOs.

In Missouri, for instance, the 23,000 pig farmer operations that existed in 1985 have dwindled to about 2,000, while the number of independent cattle farms has also dropped by 40 percent.7 The trickle-down effect put not only the small farmers out of business but also the communities that once thrived around them. The Guardian reported:8

“In 1990, small and medium-sized farms accounted for nearly half of all agricultural production in the U.S.. Now it is less than a quarter. As the medium-sized family farms retreated, the businesses they helped support disappeared. Local seed and equipment suppliers shut up shop because corporations went straight to wholesalers or manufacturers.

Demand for local vets collapsed. As those businesses packed up and left, communities shrank. Shops, restaurants and doctors’ surgeries closed. People found they had to drive for an hour or more for medical treatment. Towns and counties began to share ambulances.”

At one time, there were 1.6 million independent farms in the U.S. Today, there are about 25,000 contract farms that raise most U.S. poultry, with many of them raising upward of half a million birds annually.9

In many rural areas, there’s only one (or maybe two) big chicken companies in town, and farmers have no choice but to enter into exclusive contracts that, for many, saddle them with debt and little recourse if the relationship sours. The story is similar among big pig producers.

As noted by The Guardian, “Iowa Select Farms has one of the fastest-growing CAFO operations in the country, with 800 farms spread through half of the counties in Iowa. Yet few of the economic benefits spill down to the communities around them. Workers are often poorly paid; many are bussed in.”10

Raw Milk Can Boost Rural Economies

In sharp contrast, farmers who are able to take control of their own products and offer high-quality foods directly to consumers can often reap great rewards. Only about 3 percent of Americans (more than 9 million people) regularly consume raw milk, but the Organic Consumers Association (OCA) states this could offer a major push to rural economies.

In fact, if 100 farms in Wisconsin could provide raw milk to 50 local families, it would lead to more than $10 million in “increased wealth and well-being” for Wisconsin residents.11

OCA further noted, “A boost like that is exactly what rural economies need as U.S. dairy farmers continue going out of business at an unsustainable rate. In 1950, there were about 3.5 million farms with milking cows. By 2016, there were only 41,809. Between 2015 and 2016, 1725 dairy farms went under.”12

How Risky Is Raw Milk, Really?

Public health agencies claim that raw milk is simply too risky for your health to consume, but how dangerous is it, really? Research published in PLOS Currents revealed that while the legal distribution of raw milk has been on the rise, the rate of illnesses associated with raw milk have been on the decline since 2010.

“Controlling for growth in population and consumption, the outbreak rate has effectively decreased by 74 percent since 2005,” the researchers wrote.13

Further, citing evidence of the “immunological effects” of raw milk consumption to offer benefits against childhood asthma and respiratory illness, the researchers suggested, “given the potential for significant public health benefits which could be gained from a reduction in immunological disorders, a re-evaluation of the risk/benefit profile of unpasteurized milk is in order.”

It’s also essential to point out that leafy greens are actually the No. 1 source of food poisoning in the U.S, accounting for nearly half of all illnesses.14 But, as Civil Eats noted, “no one is calling on Americans to stop eating salads.”15CAFO meats are also notoriously dirty.

One study by the USDA Agricultural Research Service (ARS) found that chicken samples gathered at the end of production after having been cut into parts, as you would purchase in the grocery store, had an astonishing positive rate of 26.2 percent contamination with salmonella.16

Meanwhile, it’s not without irony that raw milk continues to be targeted as an unsafe food while the government-subsidized CAFO model’s illness outbreaks are minimized or glossed over. For example, a CDC report on 121 milk outbreaks between 1993 and 2006 focuses on the 73 raw milk outbreaks and barely mentions the 48 involving pasteurized milk.

That same report mentions that there were 4,413 illnesses reported as a result of drinking milk, of which 1,571 were from raw milk. But, rather than pointing out that more illnesses — 2,842 — were from pasteurized milk, they leave it for you to figure out.17 That said, many raw milk producers hold their products to even higher standards than are observed for pasteurized milk.

Take The Family Cow, for example. They run 10 milk sanitation and herd health tests, only three of which are required to sell milk to a pasteurizer. The other seven are extra tests required in Pennsylvania for those selling raw milk directly for human consumption.18

This means the milk produced by CAFOs that ends up pasteurized and shipped to grocery stores across the U.S. may very well be contaminated from the start — it’s only the pasteurization process that makes it “safe.” Raw milk, on the other hand, is required to be safe from the start.

Anti-Inflammatory Health Benefits of Raw Milk

While raw milk is noninflammatory and inhibits MAST cell release of histamines, pasteurized milk is the most allergenic food in the U.S., Mark McAfee, founder and chairman of the Raw Milk Institute (RAWMI), notes. He also points out that pasteurized milk is often associated with lactose intolerance and is often not digestible by children, whereas raw milk is highly digestible and gut-friendly.

Taken together, raw milk isn’t high risk at all but is actually very low risk, with proven health benefits. Among them is alkaline phosphatase, an enzyme found in raw milk, that’s known to be anti-inflammatory.

“[I]ntestinal alkaline phosphatase (IAP), a potent endogenous anti-inflammatory enzyme, is directly stimulated by various components of milk (e.g., casein, calcium, lactose and even fat),” researchers wrote in Medical Hypotheses,19 “… and detoxifies proinflammatory microbial components … making them unable to trigger inflammatory responses and generate chronic low-grade inflammation leading to insulin resistance, glucose intolerance, Type-2 diabetes, metabolic syndrome and obesity, known risk factors for CVD [cardiovascular disease].”

Raw milk also contains protective components that aren’t found in pasteurized milk, including antibodies and beneficial bacteria that help to kill pathogens in the milk, as well as compounds that prevent pathogen absorption across the intestinal wall. There are a variety of immune-strengthening components in raw milk as well, including lymphocytes, immunoglobulins and growth factors.20

Support Your Food Freedom and Your Local Farmers

In the U.S., efforts continue to expand access to raw milk — the only food banned from interstate commerce — and, in so doing, protect people’s right to eat and drink what they please.

If you’re interested in raw milk, in states where the sale of raw milk is legal, RAWMI lists farmers on their website who have gone through their training program and demonstrated, through testing, that their milk is consistently clean and safe.21

In other states, those who want to purchase raw milk often purchase a share of the cow or herd directly from a raw milk farmer. As with all foods, source matters, and this is just as true with raw milk as any other food, so be sure to review these tips for finding high-quality raw milk sources.

Not only are you supporting your food freedom by sourcing your raw milk from a local farmer, but you’re also helping to support a family farm and the surrounding community. The further we get from a locally based food economy, the more communities and food quality crumble.

Ultimately, even the basic knowledge of how to grow and raise food will be lost, handed over to corporate giants instead. In this way, seeking out real food from real farmers may not only save dairy farmers, but could be instrumental in saving the food supply as a whole.

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Why Magnesium Is a Cornerstone Mineral for Health

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Magnesium is the fourth most abundant element in your body,1 and one of the seven essential minerals we can’t live without.2 It’s necessary for the healthy functioning of most cells, but especially your heart, kidneys and muscles. Low levels of magnesium impede cellular metabolic function and deteriorate mitochondrial function.

As it is also required for the activation of vitamin D, deficiency may hamper your ability to convert vitamin D from sun exposure and/or oral supplementation. Unfortunately, deficiency is common and research shows even subclinical deficiencies may jeopardize your health.

If you’ve recently had a blood panel drawn, you may assume it would reveal a magnesium deficiency. However, only 1 percent of magnesium is distributed in your blood, which means a blood test is not useful to determine whether you are deficient at the cellular level.3 Recent research confirms optimal levels of magnesium are necessary for your heart4 and kidney health.5

Magnesium Deficiency Affects the Vast Majority

Statistics show that at least 50 percent of Americans are deficient in magnesium, with some estimations going as high as 75 percent overall, and as many as 84 percent of postmenopausal women being deficient in it.6,7,8 Other scientists believe the deficiency affects the vast majority of individuals based on current dietary habits, saying:9

“[B]ecause of chronic diseases, medications, decreases in food crop magnesium contents and the availability of refined and processed foods, the vast majority of people in modern societies are at risk for magnesium deficiency.”

The recommended daily allowances (RDA) for magnesium are based on age, gender and pregnancy status.10 Although it may be difficult to pinpoint the exact percentage of individuals who suffer from magnesium deficiency, data do demonstrate subclinical levels of magnesium contribute to a number of widespread health problems.

The number who suffer from deficiency increases with an aging population as the elderly tend to consume less and don’t efficiently absorb magnesium from what is eaten.11

Digestive disorders, such as Crohn’s disease and celiac, may also affect magnesium absorption.12 Individuals who suffer from Type 2 diabetes13 or use diuretics may lose more magnesium through their urine.14

As the number of people suffering Type 2 diabetes is growing, and the age at which the condition arises is getting younger,15 the number who are also at risk for magnesium deficiency is also rising. Type 2 diabetes is associated with a number of health conditions also linked to magnesium deficiency, including heart disease and kidney disease.

Magnesium Integral to Arterial Health

Magnesium is required for energy production and is a cofactor in more than 300 enzyme systems that regulate biochemical reactions, including muscle and nerve function, and blood pressure regulation.16 Magnesium also helps regulate your blood vessels and helps prevent calcification known as coronary artery calcification (CAC).

CAC is an indicator of advanced atherosclerosis, a common predictor of cardiovascular disease and chronic kidney disease.17 In 1948, researchers undertook a nearly 70-year long heart study under the direction of the National Heart Institute.

The Framingham Heart Study18 became a joint project of the National Heart, Lung and Blood Institute and Boston University with the objective to identify factors contributing to cardiovascular disease.

Magnesium Is Necessary for Optimal Heart and Kidney Health

Researchers19 recently examined data of magnesium intake in those free of cardiovascular disease at the beginning of the Framingham Heart Study and followed them over a period of 11 years.

They found a strong association between higher self-reported magnesium intake and lower calcification in the coronary arteries, which translates to lower risk of atherosclerosis and cardiovascular disease.

The researchers believe this may play a role in magnesium’s protective association in stroke and fatal coronary artery disease. The data also revealed a lower risk of abdominal aortic calcification,20 also associated with cardiovascular disease.21 A second study22 analyzed the associated risk of hypomagnesemia with diabetes and hypertension, which can contribute to a decline in kidney function.

The hypothesis was that subclinical levels contributed to a decline in glomerular filtration rate. Researchers engaged over 2,000 participants from the Dallas Heart Study. During a median follow-up of seven years, researchers evaluated glomerular filtration rate, biochemical parameters, C-reactive proteins and the prevalence of hypertension and diabetes.

The results led the researchers to conclude subclinical levels of magnesium were independently associated with decline in glomerular filtration rates indicating declining kidney function.23

Magnesium is a natural calcium antagonist and has several effects on vasodilation, regulation and changes in metabolism enhancing atherosclerotic changes in arterial stiffness, likely in part contributing to heart and kidney disease.24

Magnesium for Your Bone and Muscle Health

Magnesium contributes to the structural development of bone, and adult bone contains nearly 60 percent of the total magnesium in your body.25 As it is involved in bone formation, subclinical levels may contribute to the development of osteoporosis.

Research26 has found women with osteoporosis have lower serum magnesium levels than those without osteoporosis or osteopenia. Magnesium is also fundamental for physical performance.27 Just as it contributes to heart muscle contraction, skeletal muscles also require magnesium to relax muscle cramping and it is a cornerstone for circulatory health.

Magnesium is also important in energy regulation and plays a role in oxygen delivery and uptake in muscle. The relationship between magnesium and circulation also affects your brain. Dr. Maiken Nedergaard, co-director of the University of Rochester Center for Translational Neuromedicine, commented on the energy supply needed by the brain:28

“Our brains require a tremendous amount of energy and in order to meet this demand the flow of blood must be precisely choreographed to ensure that oxygen is being delivered where it is needed and when it is needed. This study demonstrates that microvessels in the brain play a key role in reacting to spikes in demand and accelerating the flow of blood to respond to neuronal activity.”

Magnesium Deficiency Affects Migraines, Anxiety and Depression

Although the brain is just 2 percent of your body weight, it uses nearly 20 percent of your oxygen supply in metabolic processes,29 remaining remarkably constant despite changes in mental and motor activities. Magnesium facilitates processing in the neural networks and is used to keep the blood-brain barrier healthy.30

Magnesium has proven to be essential for learning, concentration and memory and enables the brain’s plasticity, or its ability to adapt to challenges.31 Additionally, maintaining optimal levels of magnesium has proven effective in reducing the number of attacks and the number of days per month you may experience a migraine.32

In a comparison against valproate sodium, a medication used to help prevent migraine headache attacks, a randomized, controlled, double-blind study indicated 500 milligrams (mgs) of magnesium per day was an effective prophylaxis, similar to the effectiveness experienced by those taking valproate sodium, without side effects.

Anxiety disorders affect up to 13 percent of the population in the U.S.33 The condition may be debilitating, and like other mental disorders, it exists on a spectrum. Low levels of magnesium have been associated with increasing levels of noradrenaline, leading to a higher heart rate and blood pressure.

Conversely, optimal levels of magnesium may decrease the release of adrenocorticotropic hormone (ACTH), responsible for the controlled release of cortisol. Essentially, this means the release of fewer stress hormones and the modulation of the ones released.34

Optimal levels of dietary intake are also inversely associated with anxiety and depression.35 In an outpatient clinic treating 126 adults with mild to moderate symptoms, researcher found supplementation with magnesium chloride for six weeks resulted in clinically significant improvements in depression and anxiety without side effects.36

Higher Intake of Magnesium Lowers Your Risk of Vitamin D Deficiency

Vitamin D levels below 20 nanograms per milliliter (ng/mL) or 50 nanomoles per liter (nmol/L) have repeatedly been shown to raise your risk of a number of health conditions, including depression and Type 2 diabetes. According to the most recent research, a vitamin D level between 60 and 80 ng/mL (150 and 200 nmol/L) appears to offer the greatest protection against cancer and other chronic diseases.37

Adequate vitamin D levels may also help prevent or treat dry eye syndrome,38 macular degeneration,39 neurological diseases,40 fractures41 and obesity.42 Adequate levels of vitamin D also lower your mortality risk associated with heart disease,43 and may lower your risk of mortality from all causes.44

However, without adequate levels of magnesium, any vitamin D supplementation may be ineffective,45 as magnesium is required for the activation of vitamin D, and vitamin D may trigger vascular calcification if magnesium and vitamin K2 levels are not optimal.46 Higher levels of magnesium may actually lower your risk of vitamin D deficiency by allowing for the activation of more vitamin D.47

Magnesium — Supplementation and Natural Sources

One of the biggest culprits behind deficiencies is processed foods, which unfortunately has become a staple in the American diet. Some of the magnesium rich foods you may add to your diet include:48,49


Swiss chard




Bok Choy

Beet greens

Turnip greens

Seeds and nuts, such as pumpkin seeds, sesame seeds, cashews and raw almonds

Fatty fishes like wild-caught Alaskan salmon

Dried seaweed or agar

Brussels sprouts

An interesting number of factors may affect your ability to absorb magnesium from your foods. Herbicides like glyphosate act as agricultural chelators, effectively obstructing the uptake of minerals from the soil in many foods grown today. As a result, it may be quite difficult to find truly magnesium-rich foods. Cooking and processing further depletes magnesium.

Meanwhile, certain foods may actually influence your body’s absorption of magnesium. High levels of sugar intake may trigger excretion of magnesium through your kidneys, “resulting in a net loss,” according to Dr. Danine Fruge, associate medical director at the Pritikin Longevity Center in Florida.50

When it comes to oral supplementation, my personal preference is magnesium threonate, as it appears to be the most efficient at penetrating cell membranes, including your mitochondria and blood-brain barrier. Other effective ways to boost your magnesium level include:

Taking Epsom salt (magnesium sulfate) baths, as the magnesium will effectively absorb through your skin

Using a topical solution — I prepare a supersaturated solution of Epsom salt by dissolving 7 tablespoons of the salt into 6 ounces of water and heating it until all the salt has dissolved. I pour it into a dropper bottle and then apply it to my skin and rub fresh aloe leaves over it to dissolve it.

This is an easy and inexpensive way to increase your magnesium and will allow you to get higher dosages into your body without having to deal with its laxative effects.

Magnesium can be taken with or without food. If you’re also taking calcium, take them together. If you exercise regularly, consider taking your calcium and magnesium in a ratio of one part calcium to two parts magnesium with your pre-workout meal.

While the ideal ratio of magnesium to calcium is thought to be 1-to-1, most people get far more calcium than magnesium from their diet, so your need for supplemental magnesium may be two to three times greater than calcium.

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Outgoing Commissioner Unloads About Marlboro Vaping Lies

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The Marlboro brand owns nearly 40 percent of the cigarette market share.1 Marlboro is owned by Philip Morris, which in turn is owned by Altria. Altria also owns U.S. Smokeless Tobacco, makers of Copenhagen and Skoal chewing tobacco. In December 2018, Altria announced a $12.8 billion investment in Juul Laboratories, in exchange for 35 percent ownership in the company.

The acquisition also promised Juul services to accelerate the mission of the e-cigarette (e-cigs) company.2 With a declared mission to change “the lives of the world’s 1 billion adult smokers by eliminating cigarettes” and develop Juul to be “a satisfying alternative to cigarettes,”3 it may come as no surprise the company has garnered the vast majority of the e-cigarette market.4

Unfortunately, this is being achieved on the backs of children, the tobacco industry’s prime target market. If you have an addictive product, the best markets are those who will purchase it longer — or those with the longest life expectancy.

In other words, it costs more to acquire a customer who is 65 and may smoke for 15 years, as opposed to a 15-year old-who may smoke for 40 years before succumbing to an early death.

The rising number of children using e-cig vaping devices, especially the USB-shaped Juul products filled with fruit and candy flavored nicotine liquid, has been the focus of Scott Gottlieb since becoming the U.S. Food and Drug Administration (FDA) Commissioner in 2017.5 As he prepares to resign, Gottlieb expressed anger at how the industry has continued its long career of lying.

Rising Rates in Tobacco Target Market Trigger Threats From FDA Commissioner

At a recent meeting at the Brookings Institution,6 Gottlieb described how Altria, one of the world’s largest producers of tobacco products, including brands like Philip Morris, U.S. Smokeless Tobacco and John Middleton, went back on their promise to withdraw pod-based products from the market.

In a 15-page response to the Commissioner’s7 plan to address the vaping epidemic, Altria promised to hold pod-based sales for FDA approval. They withdrew some of their products but then acquired Juul months later in a $12.8 billion investment. Gottlieb commented at Brookings, saying:8

“It was a difficult meeting … It concerned me that a company that affirmed what we believe, which is that the pod-based flavored products are driving youth use, went so far as to take the product off the market and publicly make that statement … then made a substantial investment that also guaranteed that they’re going to expand the market share of the leading pod-based flavored products that’d been used by children.

There seems to be a disconnect. I assume it’s just a business decision they made to withdraw a product that didn’t have good market penetration and go on to make an investment in a similar product that did have the market penetration.”

Data from the Centers for Disease Control and Prevention’s (CDC) National Youth Tobacco Survey9 show there are 3.6 million middle and high school students who currently vape, over 1.5 million more than last year.10 The meteoric rise of vaping has overshadowed tobacco use in teenagers, escalating by 900 percent from 2011 to 2015.11

In the age group of 18- to 20-year-olds, 40 percent had not been smokers before using a vaping device. Morgan Stanley analyst Pamela Kaufman told investors,12 “Juul’s success underscores the potential for disruptive technology to undermine U.S. tobacco’s reliable business algorithm.” With the rising number of youth using Juul devices and then transitioning to traditional cigarettes, Gottlieb warns:13

“You’re going to be at overall tobacco use among children in this country, of 40, 45 percent … That is simply intolerable. I went back and looked at data back to 1950, and we haven’t seen that level of tobacco use among kids. And e-cigarettes are a tobacco product.”

Tobacco Industry’s History of Lies and Deceit Documented in Court

Beginning with what Bloomberg14 characterized as a “cautious approach,” the FDA attempted to ease regulations on the e-cigarette industry in 2017 to “encourage development of more products that could help adults quit smoking.”

However, this move didn’t do enough to prevent children from purchasing e-cig products like Juul, who reportedly owns over 75 percent of the market.15 Sidestepping the issue of selling flavored nicotine pods to teenagers is just the last in a long series of lies the tobacco industry has been telling for decades.

In 1999, the U.S. Government16 sued several large tobacco companies, including Philip Morris, now owned by Altria. For many years the tobacco industry understood the dangers to a person’s health and yet continued to sell the public on the idea that smoking was safe.

In the same lawsuit, it was claimed cigarette advertising to children younger than 21 was aimed at getting a new generation addicted to nicotine,17 to ensure new customers would replace those who died.18 In 2006, a judge found the tobacco company violated civil racketeering laws and ordered them to tell the truth in paid advertising.19

The industry delayed the court order for over 11 years and now has been forced to publish corrective statements that should appear in 50 newspapers and on major broadcast networks.20

A large challenge is most teens do not see ads in newspapers or television any longer as they consume most of their news and entertainment online. According to U.S. District Judge Gladys Kessler, examples of how the industry misled the public include:21

  • Tobacco companies falsely denied they can and do manipulate the level of nicotine in their products to create and sustain addiction, and have been since at least 1954.
  • Tobacco companies “falsely denied, distorted and minimized” the link between cigarette smoking and disease, even though they internally recognized its existence.
  • Tobacco companies concealed evidence and publicly denied nicotine is addictive.
  • Tobacco companies “falsely marketed and promoted low-tar and light cigarettes as less harmful” than regular cigarettes to keep people smoking and sustain revenues.
  • Tobacco companies internally acknowledged secondhand smoke is hazardous to nonsmokers, yet still gave false and misleading public statements denying the fact.

Altria Holds to the Letter of Their Promise but Not the Intent

In the words of Truth Initiative, the court ruled the companies22 “systematically defrauded the American people by lying for decades about, among other things, the health effects of smoking and their marketing to children.”

According to Altria,23 “Our companies include some of the most enduring names in American business …” Despite a long and lurid history of lies and deceit, the FDA believed this zebra had changed its stripes when Altria promised to remove flavored pods from the market.

Holding true to the letter of their promise, they removed pods from some existing companies, but defied the spirit of intent when they invested in Juul to take advantage of Juul’s market value and lend Altria’s asset distribution channels to Juul.

Juul Seeking Expansion in the European Union

Even though the tobacco industry was found guilty of civil racketeering and deliberately addicting their consumer base to a product they knew would ultimately cause their death, Juul has been working to develop a product to get around the European Union (EU) rules regulating the amount of nicotine delivery in e-cigarettes.24

They reportedly hope to develop a pod with lower nicotine, but increase the voltage in the device to essentially deliver a similar “hit,” as they seek to expand their market in the EU. This is yet another demonstration of the tobacco industry’s desire to circumvent the law and its lack of regard for consumer safety.

Additionally, research has found exposure to nicotine during teen years may increase the risk of addictive behavior. Researchers25 used an animal model to evaluate if rats exposed to nicotine during adolescence would grow up to drink more alcohol than those who were not exposed. They discovered exposure changes the neurological circuitry in the brain within the reward pathway.

During adulthood this function did not change in the same way it does during adolescence. The alterations in neurotransmitters are responsible for sending signals during stress, or recognizing reward. Long-term changes in the midbrain reward center may also be a gateway to other addictive drugs, such as cocaine, heroin and morphine.26

Gottlieb supports the proposed rule to cut nicotine in cigarettes to nonaddictive levels as it may cause up to 5 million adults to quit smoking within the first year after the regulation is enacted.27

City Takes Matters Into Its Own Hands

In a unique moved to protect the citizens in their city, San Francisco officials are seeking to crack down on Juul and other e-cig manufacturers. Legislation has been proposed to ban the sale of e-cigarettes within the city limits and prohibit e-cigarette companies from occupying city-owned property in the future.28

The bills’ authors are city attorney Dennis Herrera and supervisor Shamann Walton in a district that includes Juul’s corporate headquarters. This proposal is part of several actions the city is undertaking. San Francisco already bans candy- and fruit-flavored tobacco products. Voters passed that bill in 2018.

The proposed bill to ban companies selling, manufacturing or distributing tobacco products from city owned property would not be retroactive. This means Juul would maintain its current office space but would be prevented from selling within the city limits. Herrera said:29

“These companies may hide behind the veneer of harm reduction, but let’s be clear, their product is addiction. They’re in the business of getting people addicted, or keeping them addicted.”

Juul has efficiently overtaken the e-cig market with a product that effectively delivers more nicotine. To read more on how Juul’s technology has made their pens more addictive than regular nicotine e-cig pods, see my previous article, “Why the New Nicotine is Super Addictive.”

Vaping Linked to Depression and Heart Attacks

Recent research reveals vaping is taking a large toll on health, and researchers say switching to e-cigarettes is not eliminating any health risks. Data was gathered in one of the largest-ever studies conducted on the health effects of vaping to be presented at the American College of Cardiology 68th Annual Scientific Session in New Orleans.30

The research reveals adults using e-cigarettes have a significantly higher chance of myocardial infarction, coronary artery disease and depression. Previous research has been mixed, with tobacco companies advertising e-cigs as a method to help traditional smokers kick the habit.31

However, these authors compared those who do not smoke against adults who vape and found those who smoke e-cigs were 56 percent more likely to have a heart attack and 30 percent more likely to suffer a stroke.32 They were also 55 percent more likely than nonusers to suffer from depression or anxiety.

Digging deeply into the data, researchers discovered the risk rose with vaping, despite the measured frequency. Dr. Mohinder Vindhyal, assistant professor at the University of Kansas School of Medicine, Wichita, and the study’s lead author, commented on the results:33

“Until now, little has been known about cardiovascular events relative to e-cigarette use. These data are a real wake-up call and should prompt more action and awareness about the dangers of e-cigarettes. When the risk of heart attack increases by as much as 55 percent among e-cigarettes users compared to nonsmokers, I wouldn’t want any of my patients nor my family members to vape.

When we dug deeper, we found that regardless of how frequently someone uses e-cigarettes, daily or just on some days, they are still more likely to have a heart attack or coronary artery disease.”

Avoid using e-cigarettes and seek other options to help you quit smoking. In my previous article, “Vaping Shuts Off Protective Cells in Your Lungs,” I share strategies to help make quitting smoking easier.

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A Study Observing No Significant Relationship Between Exceptional Longevity and Cardiovascular Risk Factors

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Today’s open access paper illustrates one of the many issues inherent in the study of the biochemistry and genetics of exceptionally long-lived people, which is that the data from various different initiatives rarely agrees. The effects of individual or even groups of gene variants are small and hard to pin down. Past studies have suggested that exceptional longevity is correlated with a lack of cardiovascular risk factors, whether genetic or measured aspects of biochemistry such as lipid levels in blood. That seems a sensible hypothesis: cardiovascular disease removes people from the population, therefore older cohorts should exhibit fewer signs of risk for cardiovascular disease. Yet that is not the case in the work presented here: there is no good association between longevity and lesser presence of risk factors.

What this sort of distribution of results should tell us is that the biochemistry of exceptional human longevity is a poor area of study if the goal is to produce reliable therapies with large effects on human aging. Old people who survive to very late life do so largely because they are either lucky (in exposure to pathogens, in the way in which the damage of aging progressed in a stochastic manner in their case) or because they made good lifestyle choices for much of their span of years. Or both. Beneficial genetic variants and consequent differences in cellular metabolism appear to confer only very modest increases in the odds of living for a long time, and even for those people who do live longer, the impact of degenerative aging is very significant. An environment of small, unreliable effects should be skipped in favor of research strategies with larger potential gains at the end of the day.

Exceptional Longevity and Polygenic Risk for Cardiovascular Health

Exceptional longevity, defined as exceeding the average life expectancy, is multifaceted with genetic, environmental, and epigenetic factors all playing a role. Exceptionally long-lived (ELL) individuals are examples of successful ageing with a proportion demonstrating compression of morbidity. It is important to study these models of successful ageing, as these rare individuals may reveal novel longevity-associated pathways, which may ultimately translate into strategies to promote health in our ageing population.

There is evidence linking healthier cardiovascular risk profiles and lower incidence of cardiovascular disease with longevity. Analysis of lipid metabolism in longevous families identified changes in lipid concentration in the offspring of nonagenarians. Levels of apolipoproteins, important lipid transporters in the circulatory system, have been observed to decline with age. However, higher apolipoprotein levels in the exceptionally long lived have been reported, suggesting a younger apolipoprotein profile that may promote longevity.

Polygenic risk scores (PRS) for cardiovascular-related phenotypes can now be calculated due to the availability of summary data from genome-wide association studies (GWAS) examining a broad range of traits from lipids to coronary artery disease. This facilitates the evaluation of the contribution of polygenic risk for cardiovascular risk factors and disease to exceptional longevity and successful ageing. Thus, the purpose of this study was to explore the genetic profiles of ELL individuals aged (≥95 years) by assessing their polygenic risk for cardiovascular related risk and disease phenotypes relative to middle-aged controls.

This study did not confirm the hypothesis that ELL individuals have lower polygenic risk scores for cardiovascular-related phenotypes. Only the HDL cholesterol and triglyceride PRS were nominally significantly associated with ELL participants. In contrast and as expected, ELL individuals had higher polygenic risk scores for exceptional longevity (EL). In regards to the associations of the various cardiovascular PRS with EL, no findings survived correction for multiple testing. This is despite validating the utility of the lipid PRS by confirming positive associations with measured lipid levels in our sample. Interestingly, the different lipid PRS were based on GWAS that found a large number of genome-wide significant loci. ELL individuals had lower LDL and total cholesterol levels than controls in this study, but they did not differ on their respective PRS. This may suggest that environmental factors, perhaps lifestyle-related, influenced these lipid levels, which possibly promote longevity.

In contrast, the UK Biobank study observed that extreme parental longevity (defined as at least one parent who survived to the top 1% of age at death) had lower polygenic risk for several cardiovascular health measures. Namely coronary artery disease, systolic blood pressure, body mass index, high-density lipoproteins, low-density lipoproteins, and triglycerides. A similar result for HDL cholesterol and extreme parental longevity (EPL) by the UK Biobank to the current study was reported. Again, similar results were reported by the UK Biobank for LDL. However, the observed discrepancies between our analysis and the UK Biobank were most likely due to methodological differences, including the use of PRS that were based on different GWAS.

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Nicotinamide Riboside Reverses Age-Related Decline in Intestinal Stem Cell Populations

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Nicotinamide riboside supplementation is one of the ways to increase levels of NAD+ in mitochondria, thus improving mitochondrial function. This probably does little for young people, particularly young and physically fit people, but in old age NAD+ levels decline along with mitochondrial function. Mitochondria are the power plants of the cell, and with aging they suffer a general malaise that is detrimental to tissue function, especially in energy-hungry tissues such as muscles and the brain. The causes are still poorly understood, though a faltering of the quality control mechanism of mitophagy due to loss of mitochondrial fission appears to be involved. Increased NAD+ appears to override this decline to some degree, albeit without addressing any of the underlying and still problematic root causes.

In early human trials, NAD+ upregulation has been shown to modestly improve vascular function in older individuals, most likely by reversing some of the dysfunction in smooth muscle cell behavior. In mice a broader range of benefits has been demonstrated, though it remains to be seen how many of those also appear in humans to a significant degree. The work here is more along the same lines, in which researchers show that nicotinamide riboside supplementation can restore intestinal stem cell function in older mice. This should improve tissue function, but again it is worth bearing in mind that this is only overriding a reaction to the underlying damage of aging – it doesn’t fix that damage, which still carries on to produce all of its other downstream issues.

Researchers have long studied the link between aging and sirtuins, a class of proteins found in nearly all animals. Sirtuins, which have been shown to protect against the effects of aging, can also be stimulated by calorie restriction. In 2016 it was found that, in mice, low-calorie diets activate sirtuins in intestinal stem cells, helping the cells to proliferate. In a new study, researchers set out to investigate whether aging contributes to a decline in stem cell populations, and whether that decline could be reversed.

By comparing young (aged 3 to 5 months) and older (aged 2 years) mice, the researchers found that intestinal stem cell populations do decline with age. Furthermore, when these stem cells are removed from the mice and grown in a culture dish, they are less able to generate intestinal organoids, which mimic the structure of the intestinal lining, compared to stem cells from younger mice. The researchers also found reduced sirtuin levels in stem cells from the older mice.

Once the effects of aging were established, the researchers wanted to see if they could reverse the effects using a compound called nicotinamide riboside (NR). This compound is a precursor to NAD, a coenzyme that activates the sirtuin SIRT1. They found that after six weeks of drinking water spiked with NR, the older mice had normal levels of intestinal stem cells, and these cells were able to generate organoids as well as stem cells from younger mice could.

To determine if this stem cell boost actually has any health benefits, the researchers gave the older, NR-treated mice a compound that normally induces colitis. They found that NR protected the mice from the inflammation and tissue damage usually produced by this compound in older animals. “That has real implications for health. Just having more stem cells is all well and good, but it might not equate to anything in the real world. Knowing that the guts are actually more stress-resistant if they’re NR-supplemented is pretty interesting.”


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