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Activism for Longevity

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The modern community of activists and patient advocates focused on the treatment of aging, carried out to significantly extend healthy longevity, has existed in some form since the 1970s. The early decades were largely a matter of supplements and hope, however, not a real prospect for slowing aging to any sizable degree. Only in the past twenty years has the community advanced to the point at which it became plausible to meaningfully tackle the causes of aging, and only in the past ten years has support and awareness increased to the point at which earnest progress could take place.

While the first, comparatively crude rejuvenation therapies already exist in the form of senolytic compounds capable of selectively destroying a fraction of the harmful senescent cells present in aged tissues, this is but a starting point. There is a lot of work left to accomplish in the years ahead. Many more classes of rejuvenation therapy will be needed to repair or clear out other forms of damage in aging tissues, and few are as actively developed as they might be. Even as funding for research and clinical development of rejuvenation therapies increases, there will continue to be an important role for advocacy and activism: almost no amount of funding is ever enough, and all too much of it will go to the wrong sorts of programs, if the controlling parties are left to their own devices.

There is now an emerging international social advocacy movement dedicated to promotion of biomedical research and development to alleviate aging-related morbidity, extend healthy period of life, and improve healthy longevity for the elderly population. It is commonly referred to by the activists as the “longevity movement” or “longevity research and advocacy movement,” as well as “healthy life extension movement.” It is a “hybrid” between the aged rights advocacy, patient advocacy, and science advocacy, as it emphasizes the need to implement preventive medicine to improve health care for the elderly around the world via enhanced medical scientific research with a special focus on the mechanisms of biological aging.

The goals of the movement, defined by the organizations, initiative groups, and individual activists representing it, are the following: (a) to increase public awareness of the plausibility and desirability to bring the processes of aging under medical control, thus extending healthy human life span, delaying the manifestation of age-related diseases, and improving health in the older age; (b) to foster the improvement of the local and global legislation concerning health across the life course, aging, health and well-being of the elderly, and medical research with a special focus on the mechanisms of aging; (c) to allocate more public funding to fundamental and translational research on the mechanisms of aging and age-related diseases; (d) to increase the interest of the investment industry in supporting biotechnology companies developing innovative drugs and therapies targeting the underlying mechanisms of aging and thus able to prevent, delay, or cure age-related diseases; (e) to promote clinical implementation of the evidence-based medical and lifestyle means to extend healthy human life span.

The movement embraces the recent advances of biomedical science proving the possibility to intervene into the degenerative processes of aging to slow down, delay, prevent, and reverse age-related damage accumulation and seeks to enhance and accelerate such advances. The movement is still young and emerging and is not yet strongly related to other forms of health-care advocacy. But a stronger relation is hoped for.


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Extracting Evidence for Causation from the Correlation Between Excess Fat Tissue and Risk of Cardiovascular Disease

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Given a good enough data set, there are ways to produce evidence for causation in the observed relationships between patient characteristics and risk of age-related disease. While it is well accepted by now that being overweight does in fact cause a raised risk of all the common age-related diseases, a shorter life expectancy, and a raised lifetime medical expenditure, more data never hurts. Researchers have a good understanding of the mechanisms involved in these relationships. In particular, visceral fat tissue around the abdominal organs generates chronic inflammation, which acts to accelerate tissue decline and age-related dysfunction. This inflammation is perhaps largely produced through the creation of increased numbers of senescent cells, but there are numerous described mechanism with the same outcome.

Mendelian randomisation is a way of showing whether or not individual risk factors actually cause disease, rather than just being associated with it. It uses genetic variants that are already known to be associated with potential risk factors, such as body mass index (BMI) and body fat, as indirect indicators or “proxies” for these risk factors. This enables researchers to discover whether the risk factor is the cause of the disease (rather than the other way around), and reduces bias in results because genetic variants are determined at conception and cannot be affected by subsequent external or environmental factors, or by the development of disease.

Researchers studied 96 genetic variants associated with BMI and body fat mass to estimate their effect on 14 cardiovascular diseases in 367,703 participants of white-British descent in UK Biobank – a UK-based national and international resource containing data on 500,000 people, aged 40-69 years. Using Mendelian randomisation they found that higher BMI and fat mass are associated with an increased risk of aortic valve stenosis and most other cardiovascular diseases, suggesting that excess body fat is a cause of cardiovascular disease.

People who had genetic variants that predict higher BMI were at increased risk of aortic valve stenosis, heart failure, deep vein thrombosis, high blood pressure, peripheral artery disease, coronary artery disease, atrial fibrillation, and pulmonary embolism. For every genetically-predicted 1kg/m2 increase in BMI, the increased risk ranged from 6% for pulmonary embolism to 13% for aortic valve stenosis. (Above a BMI that is considered “healthy” (20-25 kg/m2) every 1 kg/m2 increase in BMI for someone who is 1.7 metres tall (5’7″) corresponds to a weight gain of nearly 3 kg)


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Vitamin K2: The Missing Ingredient for Our Bones, Arteries and More

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Vitamin K2: The Missing Ingredient for Our Bones, Arteries and More
Carol Campi, MA, DC, BSN – Life Extension Wellness Specialist

We all know how important calcium and vitamin D are for our bones. And you probably know that vitamin K is necessary for blood to clot. But did you know that vitamin K has more than one form? The various forms are called vitamers. Vitamin K1 is needed to activate various clotting factors, while both K1 and K2 play a major role in our bone and arterial health.1 Vitamin K is vital for getting calcium into our bones and keeping it out of our arteries and soft tissue.2

What is Vitamin K and Where Do We Get It?

The vitamin K vitamers are fat-soluble molecules consisting of a common ring-like structure with side chains of varying lengths. There are several differences between K1, also known as phylloquinone, and K2, or menaquinone. The K1 side chain is monounsaturated and it is primarily found in the liver, while K2 is polyunsaturated and generally found in bone, cartilage and smooth muscle. K2 is further categorized by the number of carbon groups that make up its side chains, with two common forms being menaquinone 4 (MK-4) and menaquinone 7 (MK-7).

Vitamin K1 is plant-based and can be found in many leafy green vegetables, as well as algae and plant-based oils. Menaquinones are found mostly in fermented foods and in small amounts in animal-based foods. A very high amount of K2 is found in the traditional Japanese food nattō (fermented soybeans). Gut bacteria can convert K1 to K2 in animals, but it is still unclear how much this contributes to K2 formation in humans. How efficiently humans convert K1 to any form of K2 is also under investigation and is likely dependent on one’s genetics, gut health, diet and use of drugs such as Coumadin (warfarin). 3

What is the Function of Vitamin K2?

Vitamin K is required to activate specific vitamin K-dependent proteins. One of these is osteocalcin which, when activated, supports bone synthesis. This process occurs throughout life since bone is constantly being remodeled (i.e., resorbed and regenerated).2 The MK-4 form also has the unique role of regulating the expression of various genes, including those that promote bone growth.4 Together, these actions support bone quality and may impact bone density, lessening the risk of osteoporosis.

Another vitamin K-dependent protein is matrix GLA protein which, when it becomes activated by vitamin K2, inhibits the calcification of soft tissue such as our cartilage, tendons and the smooth muscle that surrounds our blood vessels.3 This is important because when calcium deposits in our arteries, it can lead to arterial stiffness, increased blood pressure and cardiovascular events likes heart attacks and strokes.

Benefits of Vitamin K2 for Bone Health

Numerous studies have shown positive benefits of vitamin K2 for bone health. Several observation studies in Japan, where nattō is a frequent staple, found that postmenopausal women consuming the most nattō had less bone loss over time.5 A three-year randomized controlled trial (RCT) using 180 mcg MK-7 in postmenopausal women found less decline in bone mineral density (BMD) in the lumbar spine and femoral neck; bone strength was also better-maintained and there was less loss of height in the thoracic spine.6 Several studies from Japan using very high doses of MK-4 (45 mg/day—that’s 45,000 mcg!) found a decreased incidence of bone fractures in postmenopausal women with osteoporosis.3 Given that the total recommended daily allowance (RDA) of vitamin K for adult women is only 90 mcg (and 120 mcg for men), this amount is much higher than any suggested nutritional dose coming from conventional sources. It is, however, a pharmacological dose that has been deemed safe, has been repeatedly found to support the bone health of osteoporotic, postmenopausal women, and is commonly prescribed in Japan per standard of care.7

Another study on healthy postmenopausal women given a much lower dose of 1500 mcg of MK-4 versus a placebo also found significant BMD improvement and an increase in activated osteocalcin.8 Thus, it appears that vitamin K2, in both the MK-4 and the MK-7 forms, helps to maintain BMD, support bone health and lessen the risk for fractures.

Benefits of K2 for Cardiovascular Health

The 2004 Rotterdam study on 2,400 healthy men and women over 55 looked at the association of dietary intake of K2 and aortic calcification and heart disease over a seven-year period. Ingesting at least 32 mcg of vitamin K2 was associated with a reduced risk for cardiovascular disease and an approximately 50% reduction in deaths related to arterial calcification.9 The 8-year European Prospective Investigation into Cancer and Nutrition (EPIC) study consisting of 16,000 participants between the ages of 49-70 found that for every 10 mcg increase in K2, mostly in the form of MK-7 and MK-9, there were 9% fewer coronary events.10

A double-blind RCT that gave postmenopausal women 180 mcg of MK-7 or a placebo found that after three years, the women given the MK-7 had less arterial stiffness and more flexible arteries.11 These effects could translate into healthier blood pressure and better delivery of nutrients and oxygen to the tissues and organs. The placebo group from this study was also found to have a higher amount of non-activated matrix GLA protein, which correlates with increased risk for calcium being deposited within the arterial walls.

Other Important Health Benefits from Vitamin K2

  • K2 may reduce the risk of developing kidney stones by its role in activating a urinary GLA protein.12,13
  • K2 has been found to support insulin sensitivity and glycemic control in those at risk of diabetes.14
  • K2, specifically MK-4, is involved in turning on and off certain genes such as those involved in hormone production and bone growth.4
  • K2 is associated with improved outcome in certain cancer cases.15
  • K2 is found in high concentrations in the brain and may play a protective role in neurological health.15

The Relationship Between Calcium, Vitamin D and K2

Optimizing our levels of calcium, vitamin D and vitamin K2 are necessary for optimal health, especially as we age. Our bodies need 1,000-1,200 mg of calcium every day to maintain healthy bone turnover and D3 to support the absorption of that calcium from our intestinal tract into our circulation. But without sufficient vitamin K2 available to activate the vitamin K-dependent proteins such as matrix GLA and osteocalcin, much of that calcium is likely to get deposited inappropriately in our arteries, heart valves, joints and tendons, and not in our bones where it is needed.

A combination of dietary and supplemental sources can be used to get our daily calcium dosage. Ideally the amount of supplemental D3 should be determined by the amount required to maintain a blood level of 50-80 ng/mL—this will vary between people and may be anywhere from 2,000-8,000 IU (50-200 mcg) per day.16 The typical Western diet, heavy on processed foods, provides only very small amounts of K2, and even though K1 is quite abundant in green vegetables if consumed, much of it is not sufficiently converted to K2. Currently, there is no commercially available blood test for assessing K2 levels. Doses of MK-4 as high as 45 mg per day have been found to be safe and are routinely prescribed in Japan for osteoporotic women. However, based on the reviewed studies, a daily intake of 1,500 mcg of MK-4 and 180 mcg of MK-7 is likely more than sufficient.

Safety and Medication Interactions

The only safety concern for vitamin K revolves around its interaction with warfarin—a vitamin K antagonist. Warfarin and its family of anticoagulating drugs work by preventing K1 from activating various clotting proteins. Unfortunately, these drugs also interfere with the activation of matrix GLA and osteocalcin; common side effects of anticoagulants include an increased risk of aortic stenosis due to calcification and osteoporosis.17 Those individuals on warfarin should not alter their vitamin K1 or K2 intake without first consulting with their physicians. For the rest of us, unless you are fans of nattō or goose liver, it’s unlikely that you are getting adequate amounts of K2 from your diet. You may want to consider supplementing with the suggested amounts of MK-4 and MK-7 to help promote healthier bones, arteries and more.

About the author: Carol Campi, MA, DC, BSN has been a Wellness Specialist at Life Extension for the past 6 years and an enthusiast of health optimization and anti-aging science for most of her life. Her academic interests have ranged from research-based psychology to chiropractic to acute-care nursing. It was while working as an acute care nurse that she came to the realization that she could help more people by educating them on ways to prevent illness and optimize their health span. In her role as a Wellness Specialist at Life Extension she suggests and evaluates lab results, helps customers to optimize their diet with appropriate nutraceutical support and integrates conventional with holistic approaches to healthcare.


  1. Circulation. 2017;135(21):2081-2083
  2. J Nutr Metab. 2017;2017:6254836.
  3. Linus Pauling Institute. Vitamin K. Accessed 6/11/19.
  4. Thromb Haemost. 2008;100(4):530-47.
  5. J Nutr. 2006;136(5):1323-8.
  6. Osteoporos Int. 2013;24(9):2499-507.
  7. Nutrients. 2014;6(5):1971-80.
  8. J Bone Miner Metab. 2014;32(2):142-50.
  9. J Nutr. 2004;134(11):3100-5.
  10. Nutr Metab Cardiovasc Dis. 2009;19(7):504-10.
  11. Thromb Haemost. 2015;113(5):1135-44.
  12. Chin Med J (Engl). 2003;116(4):569-72.
  13. Nephrol Dial Transplant. 2018;33(3):514-522.
  14. Diabetes Res Clin Pract. 2018;136:39-51.
  15. Int J Mol Sci. 2019;20(4)
  16. Dermatoendocrinol. 2017;9(1):e1300213.
  17. Nutr Clin Pract. 2007;22(5):517-44.

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Progression of Atherosclerosis is Slowed in Mice via Targeting Senescent Cells

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Atherosclerosis is the build up of plaques in blood vessel walls, composed of fats and the debris of dead cells. Blood vessels are narrowed and weakened, and eventually something important ruptures or blocks, producing a heart attack or stroke. Cholesterols circulate in the bloodstream, attached to low-density lipoprotein (LDL) particles. The immune cells known as monocytes are responsible for ensuring that excess cholesterols stuck in blood vessel walls are removed and returned to the liver to be excreted. They do this by entering blood vessel walls, transforming into macrophages, ingesting the cholesterols, and then handing them off to high-density lipoprotein (HDL) particles.

In older individuals, increased inflammation and oxidative stress causes macrophages to become dysfunctional. Macrophages can be overwhelmed by large amounts of cholesterol, but it takes comparatively little oxidized cholesterol to turn a macrophage into a dysfunctional, inflammatory foam cell, unable to carry out its assigned tasks. Much of an atherosclerotic plaque is made up of the debris of dead macrophages, rich in oxidized cholesterols. Surviving cells signal for aid, calling in more monocytes to destruction. Chronic inflammation in blood vessel tissues makes this feedback loop run that much faster.

A sizable fraction of the chronic inflammation of aging is caused by the presence of senescent cells. These cells are created day in and day out in large numbers, and this is an important part of the normal operation of cellular metabolism. They have important roles in wound healing and cancer suppression, for example. The vast majority of senescent cells either self-destruct or are destroyed by the immune system, but a tiny fraction linger. They secrete a potent mix of signals that disrupt tissue function and produce inflammation. Fortunately, eliminating senescent cells is a going concern, with numerous approaches in human trials or under clinical development. In today’s open access paper, researchers demonstrate a novel approach to diminishing the impact of cellular senescence in blood vessel walls, thereby slowing the progression of atherosclerosis. This adds to the existing data that suggests senolytic therapies should produce benefits in this condition.

Knockdown of angiopoietin-like 2 induces clearance of vascular endothelial senescent cells by apoptosis, promotes endothelial repair and slows atherogenesis in mice

Senescent cells lose their proliferative potential in response to various stresses. They secrete a variety of pro-inflammatory mediators and proteases, gathered in the senescence-associated secretory phenotype (SASP) that engages the immune system to eliminate senescent cells. Senescent cells accumulate in aging organisms, chronic age-related diseases and benign tumors; conversely, elimination of senescent cells contributes to improve health. They also accumulate in tissues affected by atherosclerosis and their elimination strikingly reduces atherogenicity in animal models. Senescence is thus a link between molecular damage and the altered physiology of aging, and targeting SnC using senolytic drugs appears a promising strategy to reduce the burden of age-related chronic inflammatory diseases, including atherosclerosis.

Angiopoietin like-2 (angptl2) is a member of the SASP and is detectable in most organs of adult mice. Angptl2 is expressed by senescent vascular human endothelial cells (EC), but not quiescent or proliferative EC and is atherogenic when infused in young atherosclerotic (ATX) mouse models. We reported that plasma levels of angptl2 are elevated in patients with cardiovascular diseases (CVD), were associated with endothelial dysfunction, and were predictive of major cardiac adverse events and death. Recently, we reported a strong relationship between arterial expression of p21, a cell cycle inhibitor overexpressed in senescent cells and maintaining growth arrest, and circulating levels of angptl2 in atherosclerotic patients. Senescent EC are activated and promote aggregation of leukocytes, the initiating step of atherogenesis. We therefore hypothesized that down-regulation of vascular angptl2, preferentially in the endothelium of severely dyslipidemic ATX mice would promote endothelial repair and slow atherogenesis.

Here, we report that knockdown of vascular angptl2 by a shRNA (shAngptl2), delivered to the vascular cells via a single injection of an AAV1, slowed atheroma progression in ATX mice. Knockdown of angptl2 was associated with a rapid reduction in the expression of EC senescence-associated p21 accompanied by the increase in Bax/Bcl2 ratio as a marker of apoptosis; subsequently, this was associated with endothelial repair as evidenced by the incorporation of endothelial progenitor CD34+ cells. In addition to our pre-clinical results, we show that vascular ANGPTL2 gene expression is correlated with p21 expression and inflammatory cytokines in the internal mammary artery isolated from severely atherosclerotic patients undergoing a coronary artery bypass surgery. Altogether, our data suggest that targeting vascular angptl2 could be senolytic, delaying the progression of atherosclerosis.

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How to use the top 10 medicinal plants and herbs

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Before the advent of drugs, plant remedies were the go-to medicines, and they can serve you just as well today as in the past. While there are many thousands of plants, any one of which can serve a medicinal purpose, some are better known than others, and can provide relief from common ailments.

Here, I’ll review the use and benefits of 10 important herbs and medicinal plants, many of which you can grow yourself to ensure you always have some on hand.

No. 1 — Aloe vera

Aloe vera1 is a succulent plant well-known for its soothing qualities, especially for skin conditions such as burns, rashes, cuts and scrapes, but also for more serious skin conditions such as psoriasis. I have hundreds of aloe plants at my home and harvest them every day for topical use on my skin and also for eating. It is one of my medicinal plants.

In one animal study,2 an ethanolic extract of aloe vera gel had an overall antipsoriatic activity of 81.9%. Its wound healing abilities stem from the gel’s disinfectant, antimicrobial, antiviral, antifungal, antibiotic and antibacterial properties.

Properties related to a compound called glucomannan also help accelerate wound healing and skin cell growth. As an adaptogen,3 aloe vera gel may also be used internally to help your body adapt to stress.

Aloe vera contains about 75 potentially active compounds, including lignin, saponins, salicylic acids and 12 anthraquinones (phenolic compounds traditionally known as laxatives). It also provides campesterol, β-sisosterol and lupeol, and the hormones auxins and gibberellins that help in wound healing and have anti-inflammatory action.4

The pulp contains most of the healing compounds, including5,6 polysaccharides7 such as mannose (which is great for gut health and has immune-boosting benefits), essential amino acids your body needs but cannot manufacture, polyphenol antioxidants, sterols (valuable fatty acids), vitamins and minerals.

While you can purchase aloe vera gel at most health food stores and pharmacies, if you grow your own, you’ll always have fresh aloe on hand when cuts, scrapes or even psoriasis flare-ups occur. For medicinal use, be sure to select an aloe species with thick, “meaty” leaves. A good choice, and one of the most popular, is Aloe Barbadensis Miller.8

To harvest, select an outer, mature leaf, and using a sharp knife, cut the leaf as close to the base as possible. Remove the spines by cutting along each side.

  • For topical use — Simply cut a 1- to 2-inch piece off, then slice it down the middle, revealing the gel, and apply it directly to your skin. Aside from soothing burns, including sunburn, or cuts and scrapes, it also works great as an aftershave for men. For sunburn, fresh aloe gel is the most effective remedy I know of, besides prevention.
  • For internal use — If you’re going to eat it, you can use a potato peeler to peel off the outer rind, then scrape off the gel and place it in a small glass container. I like mixing mine with some lime juice. Simply blend together with a handheld blender for a delicious immune-boosting aloe shot.

While fresh aloe vera is very safe, you should not use it internally or externally if you’re allergic. If you’re unsure, perform a patch test on a small area and wait to make sure no signs of allergic reactions occur.9,10,11

No. 2 — Lemongrass

Lemongrass, an herb noted for its distinctive lemon flavor and citrus aroma, has been used traditionally to treat stomach aches, high blood pressure, common cold, convulsions, pain and vomiting.12 Lemongrass benefits listed by Organic Facts include:13

“[R]elief from insomnia, stomach disorders, respiratory disorders, fever, pain, swelling, and infections. The antioxidant activity of the lemongrass herb maintains the immune system and protects against antibiotic-resistant Staphylococcus aureus.

It even helps in maintaining optimum cholesterol levels, managing type 2 diabetes, and promoting healthy skin. It is extensively used in aromatherapy and helps combat fatigue, anxiety, and body odor.”

The leaves and extracted essential oil are the parts most commonly used, and depending on the form can be taken orally, applied topically or inhaled (as aromatherapy) for the following conditions:

Relieve stress, anxiety, irritability and insomnia by diffusing a few drops of lemongrass essential oil.14

Relax and tone your muscles; relieve muscle pain, period cramps and headaches by rubbing a few drops of the essential oil mixed with carrier oil onto the area, or diffuse as an aromatherapy treatment.

Energize tired feet by mixing essential oil and 2 tablespoons of Epsom salts in a bowl of warm water — You can also create your own foot massage oil by mixing diluted lemongrass oil with a carrier oil such as coconut oil, and adding other essential oils as desired, such as sweet almond, geranium and sandalwood.15

Treat cuts and scrapes by rubbing a small amount of diluted essential oil over the area — Lemongrass essential oil has antibiofilm properties against staphylococcus aureus16 and interrupts the growth of bacteria in the body.17

Treat gastrointestinal problems by consuming lemongrass tea or lemongrass-infused water — Lemongrass oil has anti-ulcer effects,18,19 stimulates digestion and helps regulate bowel function.20

Improve sleep by drinking a cup of lemongrass tea or lemongrass-infused water before bed.21

Relieve pain associated with headaches, muscle and joint pain, muscle spasms and sprains, either by applying diluted essential oil topically, inhaling the scent by diffusing the essential oil, or by drinking lemongrass tea or infused water.

Improve insulin sensitivity by drinking lemongrass tea or infused water — The citral present in lemongrass has demonstrated ability to regulate blood glucose and improve insulin sensitivity,22 and testing shows the citral content of decoctions and infusions are the same as that of fresh lemongrass.23 Tea is basically a weak infusion. You could also make your own lemongrass decoction. For basic instructions, see The Herbal Academy.24

Keep in mind, however, that since lemongrass essential oil can lead to lowered blood glucose,25 it may be contraindicated for people taking oral diabetes or antihypertensive medications, as well as those who are diabetic and hypoglycemic. Take special precautions if you have been diagnosed with diabetes or hypoglycemia or if anyone in your family suffers these conditions.

Treat oily hair by massaging a few drops of diluted essential oil to your scalp and let sit for 15 minutes before washing as usual.26

Fight body odor naturally — With its antifungal and antibacterial properties, diluted lemongrass essential oil can be used as a natural deodorant.

No. 3 — Dandelion

Dandelions contain vitamins A, B, C and D, and can be used as a remedy for fever, boils, diarrhea and diabetes.27 Dandelion leaf tea has diuretic, mild laxative and digestive aid properties, while tea made from dandelion roots has detoxifying properties, and can help relieve liver, gallbladder and prostate problems.28

Dandelion root is also antirheumatic, and may help dissolve urinary stones. 29 Dandelion leaves are usually picked during the spring,30 while the roots are often harvested in autumn or winter, since they’re believed to be sweeter during these seasons.31

Since dandelions are widely available and are extremely simple to grow, you can easily harvest them to make a tea of your own from fresh ingredients. You may also opt to buy tea bags made from dried organic dandelion roots or leaves.

While dandelion tea is considered generally safe to consume, it may cause allergic reactions like itching, rashes and runny nose in people who are allergic to ragweed and other related plants, including chamomile, chrysanthemums and marigold.

No. 4 — Sage

Sage has been used as a medicine for thousands of years and boasts a long list of potential health benefits, including the following:32

Aids digestion — The rosmarinic acid found in sage acts as an anti-inflammatory agent, soothing your stomach and preventing gastric spasms. Sage can help reduce the incidence of diarrhea and gastritis.

Boosts cognitive function — Research has shown even small amounts of sage, taken as food or inhaled as an essential oil, can be an effective brain booster, increasing concentration, memory recall and retention.

In vitro and animal studies have confirmed several sage species contain active compounds shown to enhance cognitive activity and protect against neurodegenerative diseases such as Alzheimer’s and other types of dementia.33

Improves bone health — Sage contains a superior level of vitamin K, which along with its high calcium content supports strong bones and teeth.

Aids diabetes management — Sage possesses compounds known to mimic the drugs typically prescribed for managing diabetes. As such, it appears to regulate and inhibit the release of stored glucose in your liver, which balances your blood sugar, helping to prevent Type 2 diabetes or assist in managing the condition if already present.

Authors of a study published in the British Journal of Nutrition34 said, “[I]ts effects on fasting glucose levels … and its metformin-like effects … suggest sage may be useful as a food supplement in the prevention of Type 2 diabetes mellitus by lowering the plasma glucose of individuals at risk.”

Promotes healthy skin — Given its many antioxidant properties, sage is useful to counteract the signs of aging such as age spots, fine lines and wrinkles. These antioxidants protect against free radicals known to damage your skin cells and cause premature aging. Some have had success using sage in the form of a tincture or topical salve to treat skin conditions such as acne, eczema and psoriasis.

Strengthens immunity — Sage contains antimicrobial properties researchers suggest, when applied in the form of an essential oil, is effective in inhibiting the growth of bacteria such as Staphylococcus aureus.35

In addition, sage is a natural expectorant and useful to clear mucus and reduce coughs.36 Consider adding a drop of sage essential oil to a cup of tea or hot water the next time you have a cold.

Treats inflammation — Antioxidant compounds in sage can help neutralize free radicals and prevent them from creating oxidative stress in your body.37 Sage is effective with respect to inflammation that affects your brain, heart, joints, muscles, organ systems and skin. To reduce inflammation, chew fresh sage leaves, drink sage tea or apply a sage tincture.

Eases pains — Sage essential oil can be used in a bath or incorporated into a massage oil to help relax muscles. When combined with a carrier oil and applied to your lower abdomen, sage essential oil can also help soothe menstrual cramps and pain.

No. 5 — Chamomile

Chamomile is one of the highest sources of the polyphenol apigenin, a powerful inhibitor of an enzyme on the surface of your cells called CD38. While CD38 is useful for your immune function it also is a major consumer of NAD+ which is the most important coenzyme in your body.

You need NAD+ to fuel another enzyme called PARP, an enzyme instrumental in the repair of damaged DNA. When you are regularly exposed to electromagnetic fields, PARP is regularly activated and consumes NAD+, which is one of the reasons it is so low in most of us, aside from the fact that simply aging tends to lower it.

When NAD+ is lowered, then PARP doesn’t function, and you don’t repair your DNA damage. This is one of the reasons why I pay attention to keeping my NAD+ levels high and why I use chamomile every night.

Additionally, the volatile oils found in chamomile flowers are said to be responsible for most of its beneficial properties,38 which include an ability to:39,40

  • Calm nerves, promoting general relaxation, relieving stress41 and controlling insomnia
  • Ease allergies, inflammation42 and infections
  • Alleviate muscle spasms
  • Relieve nausea and flatulence
  • Ease stomach ailments, gastritis, ulcerative colitis, diverticular disease,43Crohn’s disease44 and irritable bowel syndrome

Chamomile mustn’t be taken by people who are allergic to daisies, asters, chrysanthemums or ragweed. Chamomile is also known to interact with some drugs and substances, so exercise caution if you’re taking anticoagulants, antiplatelet medication, blood pressure medicines, diabetes drugs, sedatives, drugs broken down by your liver such as statins and antifungals.

No. 6 — Echinacea

Before antibiotics, echinacea was used as a general cure for various infections and wounds, including malaria, scarlet fever and syphilis.45 Centuries ago, Native Americans primarily used echinacea to help treat the common cold. Today, common uses include:

  • Boosting your immune system — The compounds in echinacea may help improve your immune system. In a study46 published in Integrative Cancer Therapies, echinacea has been shown to help reduce the severity and duration of colds if it is administered right away once symptoms appear. However, if you use echinacea several days after getting a cold, it won’t have much of an effect.
  • Fighting against bacteria and viruses — Echinacea contains a compound called echinacein, which can help against bacterial and viral infections. According to a study47 in Pharmaceutical Biology, echinacea exhibited antimicrobial properties and is effective against 15 different pathogenic bacteria and two pathogenic fungi.
  • Speeding up wound healing — When applied to a wound, echinacea may help speed up the formation of new skin cells, while helping prevent an infection thanks to its antibacterial properties. According to a study48 in the Journal of Ethnopharmacology, the compound responsible for echinacea’s wound-healing benefit is echinacoside, which is present in several varieties of the flower.

To learn more about this valuable plant and how it can benefit your health, see “10 Potential Benefits of Echinacea.” One of the easiest ways to obtain the benefits of echinacea is brewing homemade tea by simmering one-fourth cup dried echinacea flowers in 8 ounces of filtered water for 15 minutes.

No. 7 — Ashwagandha

Ashwagandha, known as a multipurpose herb and “rejuvenator,” has been used in ancient Ayurvedic and Chinese medicine for thousands of years.49 It’s a powerful adaptogenic50 herb, meaning it helps your body manage and adapt to stress51 by balancing your immune system,52 metabolism and hormonal systems.53

Ashwagandha also has natural pain reliever (analgesic) properties,54 which can help increase physical strength, and its rejuvenating effects can promote general health when used regularly.

Flavonoids and other compounds are the active ingredients that give ashwagandha its many powerful properties. In one study,55 bioactive withanolides — naturally occurring steroids — in ashwagandha were identified as agents that suppress pathways responsible for several inflammation-based illnesses, including arthritis, asthma, hypertension, osteoporosis56 and cancer.

Withanolides in ashwagandha also have immunomodulating properties,57 described as substances that can either stimulate or suppress your immune system to help fight infections, cancer and other diseases.

One of the alkaloids in ashwagandha, called somniferin, helps promote relaxation and sound sleep. A study58 at the University of Tsukuba in Japan found it can relieve insomnia and restless leg syndrome.

As an adaptogen, ashwagandha is frequently used to support healthy adrenal function, which can be adversely affected by persistent stress, be it physical or psychological. Research shows the root reduces cortisol levels, restores insulin sensitivity and helps to stabilize mood.59

Ashwagandha also supports sexual and reproductive health in both men and women, and may be used as an aid to boost your libido. In men struggling with infertility, ashwagandha has been shown to balance their luteinizing hormone,60
which controls reproductive organ function in both men and women.

It’s been shown to improve the quality of semen in infertile men,61 in part by inhibiting reactive oxygen species and improving essential metal concentrations, including zinc, iron and copper levels. Other research62 suggests ashwagandha improves semen quality by regulating important reproductive hormones.

Ashwagandha can also help boost testosterone levels in men,63,64 which can have a beneficial effect on libido and sexual performance. In otherwise healthy women, ashwagandha has been shown to improve arousal, lubrication, orgasm and overall sexual satisfaction.65

In addition, ashwagandha’s ability to rebalance hormones (including thyroid hormone, estrogen and progesterone) has been shown to improve polycystic ovary syndrome66 and relieve symptoms associated with menopause.67

Ashwagandha also has antitumor and blood production (hemopoietic) capabilities, and benefits the cardiopulmonary, endocrine and central nervous systems, all “with little or no associated toxicity.”68

Ashwagandha is contraindicated69 for, and should not be used by pregnant women, as it may induce abortion; breastfeeding women, as it may have an effect on your child; and people taking sedatives, as ashwagandha may augment the sedative effects.

Also, while ashwagandha appears to be beneficial for thyroid problems, if you have a thyroid disorder, use caution and consult with your doctor, as you may need to tweak any medications you’re taking for it. To learn more about this incredibly useful plant, see my most recent ashwagandha article.

No. 8 — CBD oil and/or whole hemp oil

The medical benefits of cannabidiol (CBD) are now increasingly recognized, and we now know the human body produces endogenous cannabinoids and that this endocannabinoid system (ECS) plays an important role in human health by regulating homeostasis between your bodily systems, such as your respiratory, digestive, immune and cardiovascular systems.

According to Project CBD, at least 50 conditions70 are believed to be improved by CBD, including pain, seizures, muscle spasms, nausea associated with chemotherapy, digestive disorders, degenerative neurological disorders such as multiple sclerosis and Parkinson’s disease, mood disorders, anxiety, PTSD and high blood pressure.

CBD is nonpsychoactive, nonaddictive, does not produce a “high” and has few to no dangerous side effects. In states where CBD is becoming widely used, there are also few reports of negative social or medical consequences, in fact, CBD has been shown to provide valuable benefits for those struggling with opioid addiction.

Endogenous cannabinoid production declines with age and, according to clinical nutritionist and expert on phytocannabinoids, Carl Germano, endocannabinoid deficiency has been identified in people who have migraines, fibromyalgia, irritable bowel syndrome, inflammatory and neurological conditions and a variety of treatment-resistant conditions.

A paper71 in Translational Psychiatry also found low levels of anandamide (one of the endocannabinoids your body produces naturally) are a statistically positive indicator for stress-induced anxiety.

According to Germano, one of your best and healthiest options may be to use whole hemp oil rather than isolated CBD (from either hemp or cannabis). The reason for this is because CBD is just one of more than 100 different phytocannabinoids found in whole hemp, and the synergistic action between them is likely to produce better results.

According to Germano, CBD alone cannot fully support your body’s ECS. You need the other phytocannabinoids and terpenes, which are very complementary to the phytocannabinoids, as well. To learn more, see my interview with him, featured in “The endocannabinoid system and the important role it plays in human health.”

In the past, before the signing of the new Farm Bill that legalizes the growing of hemp in the U.S., the leaf, flower and bud of the hemp plant could not be used in the production of CBD-rich hemp oil. The oil had to be pulled from the stalk and stem of the plant only — the less concentrated part.

With the new law, all parts of the plant can be used, which will make processing easier and more economical, as the cannabinoids are more concentrated in the leaves, flowers and buds. The law also makes it legal to grow hemp in every state, so if you wanted to, you could grow it in your backyard.

While the raw unprocessed plant could be juiced, processing will convert the cannabinoids into more usable forms. Germano offers the following advice:

“[To process it], you can take the leaf, flower and bud. You can blend it and store it in the refrigerator. Over a day or two of exposure to heat, air, light and moisture, it’ll decarboxylate to some extent and you’ll benefit more from that … [P]robably an ounce or two [of raw plant] would do the trick as a healthy plant beverage.”

No. 9 — Milk thistle

While most people consider milk thistle a pesky weed, it actually possesses remarkable medicinal benefits72,73 that make it worth keeping around. Notably, milk thistle has been prized for centuries for its anti-inflammatory, antioxidant and antiviral properties.

It is also highly regarded as a liver tonic due to high amounts of a chemical compound known as silymarin. Silymarin is a group of flavonoids known to help repair liver cells damaged by toxic substances. As such, milk thistle greatly improves the overall functioning of your liver, with specific applications related to cirrhosis of the liver, chronic liver inflammation and liver damage from alcohol and other intoxicating substances.

Silymarin has also been shown to prevent the formation of gallstones,74 support prostate health and treat prostate cancer.75 Under the direction of your doctor, you may want to consider adding milk thistle to your diet if you are dealing with a liver-based problem such as cirrhosis, hepatitis, jaundice and nonalcoholic fatty liver disease.76

Silymarin also activates AMP-activated protein kinase (AMPK), an enzyme inside your cells that plays an important role in metabolism,77 energy homeostasis and cellular repair.78 It also inhibits the mammalian target of rapamycin (mTOR)which, when chronically activated, may increase your risk of cancer.

While all parts of the milk thistle plant are edible, silymarin is contained in the seeds only. Whether or not you are able to grow your own, high-quality, organic milk thistle is inexpensive and readily available at your local health food store. Below are some ways you can incorporate this unique herb into your diet:79

  • Powdered — Use a mortar and pestle to crush milk thistle seeds into a powder that can be added to soups, stir-fries and other dishes
  • Salads — Because the entire plant is edible, you can add milk thistle flowers, leaves, roots and stalks to salads or incorporate them into cooked dishes
  • Smoothies — For a healthy liver smoothie,80 soak 2 tablespoons of milk thistle seeds in filtered water overnight; the next morning, add the milk thistle (and soaking water), 1 cup of lemon juice, one-third cup of lycium berries and 1.5 cups of ice to your blender and combine until smooth
  • Snacks — Although it may be a bit of an acquired taste, milk thistle seeds can be eaten dry, as is
  • Tea — Crush either or both milk thistle seeds and dried leaves to make a loose tea blend you can steep in an infuser with hot water; add a healthy sweetener of your choice to tone down the somewhat bitter flavor, or add a peppermint teabag for a different taste sensation81

No. 10 — Tulsi

Tulsi, also known as holy basil, is an Ayurvedic herb considered vital in India. Like ashwagandha, it’s a powerful adaptogen with antibacterial, antiviral, antifungal, anti-inflammatory, analgestic, antioxidant and adaptogenic properties, just to name a few.82

There are many tulsi products available today, including tea, tablets, powder, extracts and tulsi essential oil. Among its many benefits, tulsi may help:

Manage blood glucose levels — Tulsi has hypoglycemic and hypolipidemic effects, which may be beneficial to diabetics. One study noted that after being given the tulsi leaf powder, diabetic rats had “a significant reduction in fasting blood sugar, uronic acid, total amino acids, total cholesterol, triglyceride, phospholipids and total lipids.”83,84

Boost immunity — The leaf extract of tulsi was found to have immunotherapeutic potential in mammal subjects. The researchers noted the “crude aqueous extract of O. sanctum (leaf) possesses some biologically active principles that are antibacterial and immunomodulatory in nature.”85

Ease stress and anxiety Compounds found in tulsi leaf extract, namely ocimarin and ocimumosides A and B, have anti-stress effects.86 A test done on human subjects found that taking the plant extract may help ease generalized anxiety disorder.87

Improve dental health — Using tulsi tea as a mouth rinse may have benefits for your oral health. A study88 found an herbal mouth rinse of natural herbs like neem, clove oil, tulsi and more were able to inhibit oral bacteria like Actinomyces sp., E. nodatum, P. intermedia and more.

Boost cognitive function — One study89 found dementia-induced rats had improved cognition after being given tulsi leaf extract.

Promote liver health — Tulsi may have hepatoprotective effects, and was found to help protect against induced liver damage among rat subjects.90

Protect against different kinds of infections — Tulsi is believed to help alleviate various bacterial infections, including urinary tract infection,91 dermal infections caused by Staphylococcus aureus and other bacteria92 and respiratory tract infections like pneumonia93

Ease pain — Sipping tulsi tea may help you acquire its antipyretic, anti-inflammatory and analgesic properties. One study notes that it may be a potential alternative to nonsteroidal anti-inflammatory drugs (NSAIDs).94

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Protect your gums and your brain with K2

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Has it ever occurred to you that the overall picture of your dental health is really a reflection of your physical health? That’s the premise of Dr. Steven Lin, a dentist who uses a holistic approach and who says less-than-stellar oral health results from issues in other parts of your body.

According to Lin, if people view their mouth as the “gatekeeper” of their gut and keep their microbiome balanced and healthy, the positive results will show themselves in a healthy mouth — teeth, gums and all — and a healthier body overall.

By all means, brush your teeth after meals and floss daily, but besides looking at your teeth and your microbiome, Lin suggests that the next thing to look at is the content of your kitchen cabinets and refrigerator or, more precisely, the foods you put in them and subsequently into your mouth. Maintaining a healthy diet that includes enough vitamin K2 will benefit your teeth and gums from the inside out.

In fact, using this approach with children could ensure they grow up without such issues and even develop naturally straight teeth. For adults, focusing on the gut first could mean never having to get fillings, not to mention other dental procedures many dentists and orthodontists insist on as a matter of course.

One of the biggest problems people have in regard to gum disease is that they’re lacking in vitamin K2, aka menaquinone, which causes bleeding gums. Over time, it could mean the loss of gums and bone. But even if you begin supplying more K2 to your body, unfortunately, your gums and bone don’t grow back.

Finding the key in vitamin K2 ended up changing Lin’s approach to dentistry. In fact, Lin says it’s all related to vitamin K2, both inside and outside your teeth. He shows how gun disease can be prevented and how it can be stopped in its tracks — if it’s caught early enough — and why it’s important to cure the cause, not just treat the symptoms.

What is periodontal disease?

Lin describes his bewilderment when some patients who cleaned their teeth faithfully nevertheless suffered worsening gum disease. He began wondering if the cause went beyond just plaque build-up on teeth. The bottom line is this:

“Gum disease (periodontal disease) is a long-term chronic disease. It’s an inflammatory condition that often progresses without response to treatment. While small amounts of gum regeneration may be possible and surgical options are there, the broad answer is that it’s irreversible.”1

The term periodontium refers to two structures that comprise your gums: the cementum and the alveolar bone. Merriam-Webster2 describes the periodontal ligament (PDL) as the fibrous connective tissue layer that covers the cementum of a tooth and holds it in place in the jawbone. This is the area the disease attacks, and it occurs in stages:

  • Mild periodontitis — Gingivitis or bleeding gums
  • Moderate periodontitis — Loss of ligament attachment, pocketing or receding gums
  • Severe periodontitis — Alveolar bone loss and deep gum pocketing
  • Advanced periodontitis — Loose, mobile teeth and tooth loss

It’s clear that people who experience the first stages of gum disease are given fair warning when their gums begin bleeding, usually while brushing their teeth. Over time, perhaps a shorter time for some than others, the disease results in lost teeth.

Your gingiva is the part of your gum around the base of your teeth, which is why the first signs of gum disease, such as redness, inflammation and often pain, is called gingivitis. But what many don’t realize is that gum disease is inflammation-based, and vitamin K2 can make all the difference.

How K2 and vitamin D help your teeth, gums and more

More specifically, it signals a “loss of tolerance between your oral microbiome”3 and an unbalanced immune system. Bleeding gums are also connected to your vitamin D status. Vitamin K2 is a cofactor for vitamin D and calcium to support bone health, but it also helps reduce inflammation and the factors involved with gum disease by:

  • Decreasing the production of inflammatory markers
  • Regulating immune cells that cause inflammation
  • Decreasing fibroblast cells

Vitamin K2 and vitamin D (along with calcium and magnesium) have a synergistic relationship. Calcium strengthens your bones and enhances overall skeletal health, but only works when it gets to the right place. Vitamin K2 directs calcium into the bone and prevents it from being deposited along blood vessel walls. According to Lin, K2 mediates gum inflammation two ways:

“It decreases fibroblasts known to fuel the gum disease process. In the healing process, fibroblasts act to form scar tissue. But in gum disease, their action is harmful and could advance the calcification of periodontal ligament — an early sign of gum disease.

It activates Matrix GLA protein: This Vitamin K2 dependent protein has been shown to prevent the calcification of the periodontal ligament. Many studies have shown that Vitamin K2 has the same anti-calcification effects around the body, including in the heart, kidneys and prostate.”4

Matrix GLA protein, as explained in one study,5 is important because it inhibits calcification. To that end, there are other vital nutrients that work with K2 to promote oral health.

For example, human gingival fibroblasts (HGFs) are described in a Japanese study6 as the most abundant structural cell in periodontal tissue. Other research shows that HGFs may act as “accessory” immune cells7 that work to amplify immune responses to lipopolysaccharides,8 which are found in the outer membranes of infection-causing bacteria that cause inflammation and promote tissue destruction.

Another substance that quells inflammation is Coenzyme Q10, also known as CoQ10, which is produced in your body naturally. One study notes that CoQ10 “decreased oxidative DNA damage and tartrate-resistant acid-phosphatase-positive osteoclasts in the periodontal tissue”9 while suppressing inflammation.

The role vitamin K2 plays in your brain

Probably the most obvious way K2 makes such a difference in your oral health, then, is the way it works with vitamin D to help reduce all that inflammation and to regulate immune cells. In your brain, it may help prevent heart disease, cardiac embolism and stroke10 because matrix-GLA protein benefits both your brain and your heart.

Another way it expresses itself is through your central and peripheral nervous systems; it may even be an antioxidant in your brain, one study observes. Conversely, research shows how the drug warfarin can reduce vitamin K2 in your system:

“The relationship between vitamin K status and cognitive abilities needs to be further investigated. Notably, and despite the methodological challenges that such studies entail, it would be important to determine the long-term effect of warfarin therapy on cognitive abilities.

A potent anti-vitamin K agent, warfarin is widely prescribed for the prophylaxis and treatment of thromboembolic conditions … As individuals treated with warfarin are in a relative state of vitamin K deficiency, they could be at higher risk of cognitive problems based on the actions of vitamin K in the nervous system.”11

Vitamin K2, working with K1, seems to enhance the effects of glutathione to prevent nerve cell death as well as brain damage.12 K2 also may be significant in its role of preventing neurodegenerative damage by preventing both oxidative stress and brain inflammation.13

Lin notes that low vitamin K2 appears to negatively influence incidences of Alzheimer’s disease14 and, overall, either eating adequate K2 or taking it in supplement form is important for preventing degenerative disease and promoting optimal brain function.15

One of the effects of being vitamin K2 deficient is that it produces the symptoms of vitamin D toxicity, which includes inappropriate calcification of soft tissues that can lead to atherosclerosis.16

Osteocalcin — Crucial in healing gum disease

Lin says the first order of business in halting gum disease is calming the immune system, and at the first sign of bleeding gums, your vitamin K2 intake should increase. This is because your ability to repair damage from gum disease is dependent on the release of vitamin K2-activated proteins.

That’s where osteocalcin comes in. Osteocalcin17 is a protein hormone found in bone and dentin. Gum tissue releases it where there’s inflammation and gum disease, particularly in postmenopausal women.18 In fact, it’s crucial for your body’s ability to heal gum disease.

If you’re deficient in vitamin K2, your body may release osteocalcin, but it won’t be active. Osteocalcin also increases your insulin sensitivity,19 so Type 2 diabetes and advanced gum disease are both associated with this protein. According to Lin:

“Vitamin K2 has a critical role in bone loss in both gum disease and osteoporosis. Vitamin K2 inhibits bone loss through resorption by inducing osteoclast apoptosis. The severity of bone loss in gum disease is worse in the presence of osteoporosis.”20

Lin says that while further studies are needed, gum disease and vitamin K2 are linked because K2 is a central mediator in inflammation, immune regulation, matrix-GLA protein and osteocalcin. Anyone noticing bleeding gums or advanced stages of gum disease can consider taking vitamin K2 supplements, but also to begin eating more foods that will help supply it.

How to get more vitamin K2

Foods with significant amounts of vitamin K2 are rare, Lin adds, so you need to be intentional about it because you’re probably not eating enough. It’s important to know that how foods that contain K2 are treated and prepared because this makes a difference in the amount that is ultimately made available to your body.

With that in mind, Lin explains that if K2 is derived from animals, they must be pasture raised. Brie and Gouda cheese, for instance, are particularly high in K2, as is grass fed butter or ghee and organic, pastured eggs. Lin’s partial list of K2-rich meats21 include:

  • 2 to 2 oz. of pastured chicken, duck or goose liver pate
  • 6 to 12 oz. of pastured chicken legs or thigh meat
  • 2 to 3 slices of organic, grass fed beef or lamb liver

One reason you want to choose only pastured beef is because if cows are fed soy or grains, they won’t get K1, which means they won’t be able to convert it to K2. If cows eat “dead” hay that no longer has the proper nutrients, they may not produce K2-rich dairy products. In addition, Lin says:

“One dozen eggs a day from caged hens won’t supply enough K2 for your daily requirement, whereas two to four eggs a day from pasture-raised hens may provide adequate K2 … Fermented foods also provide a different form of vitamin K2, however it needs to be cultured properly and then stored in a refrigerator, not pasteurized or contaminated. Today we eat far less fermented food rich in Vitamin K2.”22

In the plant world, leafy greens are an excellent source of vitamin K1, and your choices come from more than just types of lettuce. They extend to turnip greens, mustard greens, collard greens, beet greens and, of course, spinach and kale.

Needless to say, though, organic greens are optimal choice, in light of information from the Environmental Working Group’s 2019 Dirty Dozen23 list: The plant-based foods with the heaviest toxic load from pesticide overspray include spinach and kale in the No. 1 and No. 2 spots.

For vitamin K2, however,24nattokinase (natto), which is fermented soy, is one vegetarian source of vitamin K2. Fermentation removes the disadvantages associated with eating raw or cooked soy. Other good sources of K2 include vegetables fermented at home using a starter culture of vitamin K2-producing bacteria.

If you think you may not be getting enough vitamin K2, besides eating grass fed raw dairy products, meat, eggs and fermented foods, supplementing is another option, but it should be menaquinone-7, or MK-7, a form of vitamin K2, which stays in your liver and helps support strong bones, but also helps reduce incidences of heart disease and cancer.25

I recommend getting around 150 micrograms (mcg) of vitamin K2 per day, although others recommend slightly more, such as 180 to 200 mcg per day.

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Changing Macrophage Behavior to Improve Regeneration Following Heart Attack

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The innate immune cells known as macrophages play an important role in the coordination of regeneration, in addition to their tasks related to defense against pathogens and clearance of debris and molecular waste. Macrophages adopt different polarizations, or collections of behaviors, under different circumstances. Researchers are very interested in finding ways to force macrophages to adopt a desired polarization, such as to switch inflammatory, aggressive macrophages into a kinder, gentler pro-regeneration state. The research noted here is an example of those efforts, in that the scientists involved are attempting to make macrophages participate more readily in the regrowth of blood vessels following damage to the heart, such as that produced by a heart attack.

Despite the advent of new therapeutic strategies to restore blood flow, we are not yet able to prevent the onset of heart failure following myocardial infarction (MI). Hence, it is a major challenge to identify innovative strategies to restore nutrient supply to the infarcted myocardium, ultimately aimed at regeneration of myocardial functionality. The cellular response following MI is characterized by a rapid recruitment of neutrophils. Their arrival is superseded by the infiltration of classical monocytes, which contribute to clearance of debris. However, this subset also drives robust inflammation, leading to pathological remodeling. In contrast, the appearance of nonclassical monocytes and reparative macrophages marks a turning point between inflammation and its resolution, as these cells govern repair and angiogenesis. At this point, knowledge about mechanisms regulating this cellular switch and about origin and identity of molecular cues involved is scarce.

Annexin A1 (AnxA1) is quickly released upon cellular stress; it acts through Formyl peptide receptor-2 to prevent chemokine-mediated integrin activation, and thus, turns off inflammatory recruitment of myeloid cells. AnxA1 also activates pro-repair mechanisms by activation of Rac1 and NOX1, resulting in enhanced epithelial cell migration after injury. Local intestinal delivery of an AnxA1 fragment encapsulated within polymeric nanoparticles accelerated recovery following experimentally induced colitis. With its central position during the switch from inflammation to resolution, we hypothesized that AnxA1 may be an important cue linking initial myeloid cell recruitment to myocardial repair.

AnxA1 knockout mice showed a reduced cardiac functionality and an expansion of proinflammatory macrophages in the ischemic area. Cardiac macrophages from AnxA1 knockout mice exhibited a dramatically reduced ability to release the proangiogenic mediator vascular endothelial growth factor (VEGF)-A. However, AnxA1 treatment enhanced VEGF-A release from cardiac macrophages, and its delivery in vivo markedly improved cardiac performance. AnxA1 has a direct action on cardiac macrophage polarization toward a pro-angiogenic, reparative phenotype. AnxA1 stimulated cardiac macrophages to release high amounts of VEGF-A, thus inducing neovascularization and cardiac repair.


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Linking the DNA Damage Response and Calcification of Arteries

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Researchers here provide evidence for a specific mechanism that can link the oxidative stress of aging with calcification of tissues such as arteries. Calcification reduces elasticity, which in the case of blood vessels contributes to hypertension, but it can also cause serious functional issues in other tissues. Oxidative molecules are generated in increasing numbers in aged tissues, and where their presence outweighs the existing antioxidant defenses over the long term, disruption results. The deeper causes of this oxidative stress include chronic inflammation, such as that produced by senescent cells, and mitochondrial dysfunction. As the example here shows, the consequent disruptions produced by oxidative stress include maladaptive responses in the regulation of cellular behavior.

Biomineralization is the deposition of mineral particles within a proteinaceous organic matrix. In bone, this is an essential physiological process, but extensive pathological calcification of soft tissues, in particular the vasculature, commonly occurs in association with disease. Determining how this complex chemical process is controlled is relevant to both bone development and the treatment of detrimental conditions such as “hardening of the arteries.” Despite increased understanding of the cell biological processes involved in biomineralization, the chemical mechanism of mineral nucleation remains elusive.

Studies in vitro have shown that the formation of bone-like ordered mineral deposits around collagen fibrils requires other factors such as additional or substituting mineral ions or non-collagenous biomolecules. This implies that there is cellular control of extracellular matrix (ECM) calcification through the secretion of specific factors, but the identification of these factors remains elusive. In both bone and the vasculature, biomineralization is accompanied by osteogenic differentiation of resident osteoblasts and vascular smooth muscle cells (VSMCs), respectively. Osteogenic differentiation results in increased expression of multifunctional acidic proteins, including the small integrin-binding ligand, N-linked glycoprotein (SIBLING) proteins, and speculation has focused on these “osteogenic” proteins as specialist molecules that may selectively bind calcium ions and provide specificity of interaction with collagen fibrils, these proteins do not have the calcium concentration capacity to induce collagen calcification.

Previously we discovered that poly(ADP-ribose) (PAR) is abundant in the calcifying growth plate of developing fetal bone, which led us to hypothesize that PAR may play a role in biomineralization. PAR is a post-translational modification moiety composed of sugar phosphates that is produced by PAR polymerase (PARP) enzymes and adducted to numerous cellular proteins in a process known as PARylation. Several characteristics of PAR lend support to its possible extracellular role in biomineralization: first, the pyrophosphate groups of PAR are predicted to locally bind calcium ions, potentially to the levels needed for mineral nucleation. Second, PARP1 and PARP2, the dominant PAR-producing enzymes, are expressed in response to DNA damage and oxidative stress, both etiologies associated with vascular calcification. Third, emerging evidence suggests that osteogenic differentiation in calcifying osteoblasts is regulated by PARP activity induced by hydrogen peroxide release from cells. Therefore, we explored whether PAR could control the physicochemical process of mineral formation in the ECM and provide evidence that PAR biosynthesis, induced in part by the cellular DNA damage response (DDR), is a unifying factor in physiological bone and pathological artery calcification.


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Discussing the DNA Damage Hallmark of Aging at Long Long Life

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The Long Long Life team will be putting together a set of videos in the months ahead, one for each of the Hallmarks of Aging. The first to be published covers the hallmark of DNA damage, stochastic mutational change to nuclear DNA that is widely thought to make a meaningful contribution to the dysregulation of cell behavior in aging. This is evidently the case for cancer risk, as cancer is caused by mutations that enable rampant, unregulated growth, but may only be important otherwise when mutations occur in stem cells or progenitor cells that are able to propagate the mutations widely in tissues.

The Hallmarks of Aging is a list of common processes and outcomes found in aging, and considered by a sizable fraction of the research community to cause aging. While the hallmarks overlap with the list of forms of cell and tissue damage described in the earlier Strategies for Engineered Negligible Senescence (SENS), a view of aging as accumulated molecular damage, the two differ in that some of the hallmarks are clearly not fundamental causes of aging in the SENS view. They are some way downstream from the forms of molecular damage that would be considered true causes of aging. For example, the hallmarks include loss of proteostasis and dysregulation of nutrient sensing. Both of these are managed by collections of cell behaviors and states; we must ask what causes those behaviors and states to change, and the answer must be some form of underlying damage.

[Video] The 9 Hallmarks of Aging, episode 1, DNA damage

The first cause of aging that we will address are the damage to our DNA over time. DNA is the medium of information that makes us who we are, the manufacturing program of our body. This information is made up of genes and all genes are grouped together under the name “genome“. All this information must be transmitted from one cell to another when they divide to generate daughter cells. And for that, it is necessary to replicate the DNA integrally at each cellular division.

Unfortunately, even this very powerful replication system is not without errors. It has been noted that DNA errors accumulate in life, as many factors influence the stability of the genome. These factors are varied and can be external, such as smoking, sunlight, food … but also internal, such as replication errors: when your body has to copy the information contained in your DNA, it makes mistakes. These errors can either be repaired, cause cell death, or, and this is the problem, be transmitted to daughter cells.

Fortunately, we have repair systems. Some genes build proteins to repair replication errors, but sometimes the replication errors affect the genes that make these repair systems and, through a snowball effect, there is an exponential growth of problems within the cell. In mice and humans, it has been shown that there is a causal link between DNA damage accumulation and aging. In fact, when the cells in our body divide a large number of times and are carriers of genetic mutations, this causes a dysfunction of the cell that can cause problems at the level of the organ concerned.

Interestingly, it has been shown that during aging, repair systems (such as the PARP protein) become much more abundant in cells, suggesting that our body is aware of the deregulations that come with age and tries to take the necessary steps to fight them. The activity of these repair systems is however dependent on co-enzymes, small molecules that allow them to function. These are essential fuels for our cells whose concentration and recycling decreases with age. Among them, NAD+ is often mentioned, because it is essential to repair mechanisms, but also to mitochondrial health. When these molecules eventually run out, our repair systems no longer work well, leading to serious disruptions, not only in replication but also in other mechanisms, up to and including cell death.

Supplementing with NAD+ may be a good idea to boost our repair systems but it is also possible that cell suicide linked to NAD+ depletion is a protection of the body against cells that have become genetically diseased and that it would be preferable to eliminate. Researchers have used mice, which have been treated to keep a constant level of NAD+ throughout their lives. And not only the treated mice lived healthier lives but they also lived longer than the untreated mice. This shows that, in mice in any case, upregulating NAD+ seems to be a good idea to fight against aging. In humans, as usual, this remains to be proven.

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Dr. Weil on the development of integrative medicine in modern practice

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Dr. Andrew Weil, director of the University of Arizona Center for Integrative Medicine, is one of the true pioneers of this field, having advocated holistic approaches to health for about 50 years.

“I was always interested in science and biology,” Weil says, and “I have a lifelong interest in plants … that led me to be a botany major at Harvard as an undergraduate and started me on a career interest in medicinal plants.”

Fascinated by mind-body interactions, Weil began studying alternative medicine in college. After graduating medical school, he did a yearlong fellowship with the National Institutes of Health. He also did a fellowship with the Institute of Current World Affairs, which allowed him to travel around Latin America and Africa to collect information on medicinal plants and traditional healing.

“I chased around the world looking for healers and to see what I could learn because I felt that what I had learned in my conventional medical education wasn’t going to serve me. I saw the methods do too much harm, and I had learned nothing about keeping people healthy,” Weil says.

“The irony is that when I finished traveling and landed back in Tucson, it turned out the person who had most to teach me had been here all along. That was Dr. Robert Fulford. He was a doctor of osteopathic medicine (D.O.). He was then in his 80s and a master of cranial therapy.

He really made me aware of the healing power of nature. I am an enormous fan of osteopathic manipulation and cranial therapy. I recommend them a lot. I hope more D.O.s will go back to their roots and again practice manipulation …

After I finished my internship, I took a course at Columbia University on medical hypnosis — one of the most interesting courses I ever took. As a result of that, I also make frequent referrals to hypnotherapists. I have, again and again, seen how changes in the mental realm initiate healing and affect the physical body.

To me, that’s one of the great limitations of the dominant scientific and medical paradigm, which only looks at the physical as being real and believes that changes in the physical system must have physical causes to be physical. Nonphysical causation of physical events is not allowed for. Integrative medicine philosophy challenges that materialistic paradigm.”

The emergence of integrative medicine

It wasn’t until the 1990s that medical institutions began opening up to Weil’s methods. “I had a large following in the general public, but none of my medical colleagues paid any attention to me,” he says. In the ’90s, however, health care economics began faltering, forcing institutions to start listening to what patients really wanted.

At a fundamental level, integrative medicine is the solution to the desperate problems and complications of chronic degenerative disease experienced in the U.S. Conventional medicine is really ineffective when it comes to these issues. As for the best way to help conventional physicians embrace these strategies, Weil says:

“My focus has been on training physicians and allied health professionals through the University of Arizona Center for Integrative Medicine. We have a two-year intensive fellowship. We now have 1,800 graduates: highly physicians, nurse practitioners and physicians’ assistants in practice in all states and in a number of other countries.

Many of them are now training other people. We also have a curriculum in integrative medicine in residency training that’s now been adopted by 70-some residency programs around the country (as well as in Canada, Germany and Taiwan).”

While 1,800 doctors are a drop in the bucket — a fraction of a percent of the 1.1 million physicians in the U.S.1 — they are important change agents.

“I think for things to change, there has to be a grassroots sociopolitical movement in this country, in which enough people get angry enough about the way things are,” Weil says. He hopes the growing numbers of health professionals trained in integrative medicine will catalyze that movement.

We also need to elect representatives who are not beholden to the vested interests that want the system to go on as it is. Those interests are blocking the implementation of more effective and less expensive strategies.

“We may have to have a total crash of the health care system for things to change,” Weil says. “To every graduating class of our fellows, I say, ‘You are the ones who could start this movement in the country.’ Doctors are victimized by the current system. They should be marching in the streets, demanding change.

As dysfunctional as our health care system is, it’s generating rivers of money. That money is flowing into very few pockets — the pockets of Big Pharma, the manufacturers of medical devices and the big insurers. Those vested interests have total control of our representatives …

I think doctors today are so unhappy. I hear many, many doctors say they wish they hadn’t gone into medicine. They’d never let a son or daughter of theirs go into medicine. I never heard anything like that when I was in college. Medicine looked like a very desirable profession. You could be your own boss. You were highly regarded in society.

All that has changed. Throughout history, much of the satisfaction of practicing medicine derived from the therapeutic connection with the patient, the getting to know someone. All that has evaporated in this era of for-profit, corporatized medicine. The time allowed for medical visits gets shorter and shorter.

The main obstacle is that our priorities of reimbursement are totally backward. We happily pay for drugs, for invasive procedures, for diagnostic testing. We don’t pay health professionals to sit with patients and talk to them about diet or teach them breathing exercises. That has to change.

Of course, we also need to have data to show to the people who pay for health care that integrative approaches using lifestyle modification and natural therapies save money and produce outcomes that are equal to or better than those of conventional medicine.”

Breathing basics

One of Weil’s health strategies is a simple breathing technique called “The 4-7-8 Breath.” “I teach that whenever I get the chance. I’ve done it with all my patients. I teach it to all our fellows. I do it with friends. I teach to all groups I speak to,” Weil says.

“It’s breathing in through your nose to a count of 4, holding your breath for a count of 7, blowing air out through your mouth to a count of 8, and doing this for four breath cycles at least twice day day. You have to practice it regularly. It is the master key to changing the activity of the involuntary nervous system,” he explains.

“Of all the remedies that I’ve given to patients over the years, the one that I’ve gotten the most positive feedback about is that simple technique. It costs nothing, uses no equipment, takes very little time. Medical doctors don’t take it seriously because they don’t believe that something so simple — something that does not involve a drug or device — can change anything in the body. For that reason, little research has been done on breath work.

I do the 4-7-8 breath at least twice a day — when I wake up and when I go to sleep — and any time during the day that I feel that I want to focus and relax. (I now do eight breath cycles at a time and don’t recommend any more than that.) One result that I’ve seen in myself: I have a very low heart rate. It’s usually in the low 40s, sometimes in the high-30s.

I exercise regularly, but I’m not fanatical. I swim and walk every day. But up until maybe 20 years ago, my heart rate was around 70. The only way I can explain the change is that it is a result of doing that breathing exercise regularly. It has increased my vagal tone, slowed my heart rate and kept my hands very warm most of the time. It’s the power of the relaxation response — one of the great rewards of doing this breathing practice.”

Aside from activating your parasympathetic nervous system, which increases your heart rate variability, proper breathing will help improve your digestion and blood circulation and lower high blood pressure.

Maintaining cognitive and physical health into your senior years

At 77, Weil is also a testament to the cognitive benefits of this and other holistic techniques. His mental acuity for someone in their late 70s is truly remarkable, and doesn’t seem to have changed since his youth. When asked what he attributes his general health to, he says:

“I get good rest and sleep. I use supplements wisely. I’m a great believer in the power of mushrooms. I take a number of mushroom products that I think are helpful both mentally and physically. I eat a lot of fermented foods. You know there’s increasing research on the connection between the microbiome and mental-emotional well-being.

I think that’s another strategy. And I drink matcha green tea every day. (I am so much a fan of it that I created a company — Matcha Kari — and got the URL to bring high-quality matcha from Uji, Japan, to people in this country.

I spend time with people who are active and happy and positive and I think that’s a great strategy as well. I have two companion animals, two wonderful dogs that I spend a lot of time with. I attribute a lot of my well-being to living with them as well.”

Among Weil’s favorite medicinal mushrooms are turkey tail and lion’s mane. Turkey tail has a number of cancer-protective effects, both preventively and therapeutically, while lion’s mane contains a unique nerve-growth factor. “I recommend it to people with neuropathy,” Weil says. There’s also evidence suggesting lion’s mane can help improve cognitive function.

True food kitchen

Last year, I had the opportunity to try out the True Food Kitchen while at the Paleo f(x)™ conference in Austin, Texas — a restaurant chain Weil conceptualized. He explains:

“I’m a very good home cook. I’m not a chef. But over the years, many people have said, ‘You ought to open a restaurant.’ I was never tempted to do that because I know nothing about the restaurant business, and it looked like a very tough business.

But about 11 years ago, a mutual friend introduced me to a very successful restaurateur in Arizona, Sam Fox. I proposed the concept of a restaurant that would serve wonderful, delicious food that was also healthy. His immediate reaction was, “Health food doesn’t sell.”

I think he thought I meant tofu and sprouts. He regarded me as a hippie and didn’t see any possibilities for a collaboration. I invited him and his wife to my home. I cooked a meal for them. They liked the food. His wheels began to turn, and he said he would give it a try, but he was very skeptical that the concept would succeed.

We opened our first True Food Kitchen in Phoenix 11 years ago. It was a success right out of the gate. There are now 29 of them around the country. People love the food. We still don’t have any real competition. The menu is based on my anti-inflammatory diet, with something for everyone there.

You can go with a mixed group. There are meat entrees — although not many of them — wonderful produce and fish. Gluten-free people can get what they want, people who are vegans, paleo or keto can find what they want there. It’s been a great delight to see people liking the kinds of food I’ve enjoyed most of my life.”

We certainly need more restaurants like that, because eating too much processed food is one of the key challenges most people have. While you may not think of restaurant food as processed, a vast majority of it is.

Staying active is a key component of longevity and health

About 50% of 80-year-olds experience sarcopenia, loss of muscle mass. As noted by Weil, one of the key prevention strategies for sarcopenia is to stay active and use your muscles as much as possible. This is also why strength training is so highly recommended for seniors.

“I use my muscles a lot,” Weil says. “I am careful in what I do, but I go up and down stairs a lot when I get the chance. I lift things. I don’t feel that I’ve lost muscle strength. I certainly have more aches and pains than I did when I was younger, but I think my musculoskeletal system is in good shape …”

“It’s important to pay attention to how your body changes and how it reacts to different things … In my 20s, I ran for a time — until I got signals from my knees that they didn’t like that. I shifted to cycling and did that for a long time. And then I got into swimming, which agrees with me very much. I think it’s good to be flexible and open to change …”

Integrative medicine is the answer to many growing problems

Like me, Weil sees integrative medicine as the way of the future. “I’ve always said that one day we’ll be able to drop the word ‘integrative’ and it’ll be just ‘good medicine,'” he says. He believes this transition is inevitable, because the forces that are taking down our health care system continue to build.

This includes a growing population of seniors, uncontainable health care costs due to our dependence on expensive technologies and drugs, and growing epidemics of lifestyle-related disease that conventional medicine cannot successfully manage.

“This is happening all over the world, but it’s most advanced in the U.S.,” he says. “Our health care system is farther over the cliff. At the same time that we are paying more for health care than any other people in the world — now 18% of our GDP — we have worse health outcomes than any other developed nation. The World Health Organization ranks us 38th, on par with Serbia. Something is very wrong with that picture. It’s unsustainable.”

On cannabis

One positive change is the growing acceptance of medicinal marijuana and hemp, the latter of which was legalized in the 2018 Farm Bill. While Weil no longer uses cannabis, he recounts his personal history with the plant during his 30s. He also conducted the first ever double-blind human experiments with cannabis, which were published in the journal Science in 1968.

“We’ve been very stupid in our relationship with that plant,” he says. “Cannabis sativa — the word ‘sativa’ means useful — is amazingly useful. It gives us a very high-quality oil and an edible seed, a medicine, an excellent fiber and an intoxicant. That’s a lot of ways for one plant to serve us.

We have let a multibillion-dollar industry in hemp textiles slip away to China, a multimillion-dollar industry in edible hemp products go to Canada. We have rejected cannabis as medicine for a long time. I’m very happy to see this change.

I regard cannabis as the plant world’s equivalent of the dog. Dogs long ago decided to co-evolve with us. Cannabis has done the same thing. We can’t unravel the ancient history of cannabis, because as far back as we can look, it’s always been associated with human settlements and human activity.

It wants to do nothing other than to serve us. It lets us manipulate its genome. It just wants to help us and we have turned it away. It’s nice to see that change.”

Psychedelics may have a place in medicine

Weil also believes there’s a place for psychedelics, such as magic mushrooms. “The great magic and potential of psychedelics is that they can show you possibilities that you otherwise would not have believed,” he says. However, once you’ve touched on these new possibilities, he says you need to find other, nondrug ways to re-experience or maintain them.

“If you try to use the drugs as the sole method of having them, they fail you,” he warns. “The example I have written and talked about [is] when I was about 28, I wanted to learn to practice hatha yoga. I worked with a number of postures.

The one I had the most difficulty with was the plow — where you lie on your back and try to touch your toes on the floor behind your head. I worked at this for a long time and I got my toes to within a foot of the floor but no further, because I would have excruciating pain in my neck. No matter how I persisted, I couldn’t make further progress.

One spring day, I took a dose of LSD with friends in a beautiful outdoor setting. I felt terrific. My body was completely elastic and flexible, and I thought I ought to try that yoga pose. I lay down, got my feet over my head and lowered them. I thought I had about a foot to go and they touched the ground. I couldn’t believe it. I raised and lowered them. It was a source of such delight.

The next day I tried to do it and I got my toes within a foot of the floor and had a horrible pain in my neck. But now there was a difference. I had seen that it was possible. I was motivated to keep at it and, in a few weeks, I was able to do it. If I had not had that experience, I don’t think I would have kept up the practice. To me, that’s a model of how these drugs work. They can show you possibilities.

I think they have tremendous potential in medicine. Everyone looks at their use in psychotherapy, and that’s fine, but I think they have a tremendous potential to change how people experience their bodies. For people who have chronic diseases, a structured psychedelic session can show them that it’s possible to be without pain or other symptoms. And that can motivate them to figure out how to maintain the improvement in other ways.”

More information

While Weil says he’s done writing books, he’s in the process of writing a collection of stories from his life. The University of Arizona Center for Integrative Medicine in Tucson, which he still heads up, is also entering a new phase of growth.

“The university has made a solid commitment to make integrative medicine a top priority,” he says. We will get a dedicated building on campus and will open the first integrative medicine primary care clinic in Tucson early next year.

You can find more information about this on the Andrew Weil Center for Integrative Medicine website. There, you can also sign up for online courses to explore topics such as nutrition, integrative pain management, cardiovascular health management and more. There’s also a research section you can peruse to learn more about the benefits of integrative medicine.

“We think we have a model that is replicable, sustainable, profitable that can be eventually replicated throughout the health care system here and elsewhere. We’re expanding our teaching programs. We have a very strong research initiative as well.

This is all very exciting — something I’ve waited for, for a long time … I think the future is going to be very bright for our field. Medicine doesn’t change as a result of intellectual argument. It changes as a result of economic necessity. And time is on our side.

Our health care system is in deep, deep trouble. The wisdom of what [Dr. Mercola] and I have been advocating for so long will become more and more apparent as the health care crisis deepens.”

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