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  • Osteoporosis & Resveratrol

    December 29, 2017: by Bill Sardi

    You can fool some of the people all of the time
    and all of the people some of the time
    but you can’t fool all of the people all of the time.
    Except when it comes to calcium.

    When it comes to preventing age-related bone loss, the obvious escapes attention.  Osteoporosis or age-related bone loss largely occurring in females is due to a shortage of estrogen, not calcium as both doctors and consumers mistakenly believe.  Because of this most trials fail to show supplemental calcium maintains bone density.

    A recent meta-analysis of randomized clinical trials concluded the use of supplements that included calcium, vitamin D, or both compared with placebo or no treatment, was not associated with a lower risk of fractures among community-dwelling older adults.  This analysis did not support the routine use of mineral and vitamin supplements for prevention of fractures in older adults.

    With adequate dietary intake of calcium from the diet, no strong repeatable evidence among postmenopausal women exists to justify calcium supplementation.

    The big fat calcium mistake

    In spite of the negative or null calcium studies, $1.15 billion of calcium supplements were sold in 2015.   Global sales of calcium pills were $6 billion in 2013.  Over half of older Americans take calcium and vitamin D supplements, either prescribed or over the counter, and bone health is the most common specific motivation for use of nutritional supplements.

    Calcium supplementation is so embedded in the clinical practice of medicine that there is no stopping it.  Leave it to modern medicine to embrace dietary supplementation when it fosters more disease to treat.

    Recommendations for calcium intake from the diet and supplements ranges from 700-1200 milligrams per day.

    An estimated 10 million Americans take calcium pills.

    Eighty percent (80%) of osteoporotic Americans are women.

    An authoritative report published in the British Medical Journal in 2015 says: “increased calcium and vitamin D intake should not have been recommended for older adults living independently after 2007.”

    Logic and the obvious escape attention.  Women don’t cease consuming calcium in their diet in unison as menopause approaches.  It is a shortage of estrogen, not calcium, that is responsible for postmenopausal bone loss.

    In an anticipated “knee-jerk” reaction to protect the business interests of its members, The Council for Responsible Nutrition that represents dietary supplement companies issued a statement saying that “negative studies should not cause consumers to doubt the value of calcium supplements for maintaining bone health.”

    So there is polarization between commercial interests and the research.

    The National Osteoporosis Foundation, which needs to make some kind of recommendation beyond just throwing up its hands, says research studies “support the use of calcium plus vitamin D supplements as an intervention for fracture risk reduction in both community-dwelling and institutionalized middle-aged to older adults.” But again, that statement is made without adequate scientific backing.

    The trouble with calcium pills

    Calcium supplements are not just ineffective they are problematic.

    Believe it or not, adverse symptoms of calcium supplementation such as constipation (remedied by balancing with magnesium) and abdominal pain exceed that of placebo tablets.  In controlled trials, hospitalizations for gastrointestinal side effects were 6.8% for calcium pills and 3.6% for placebos.  The occurrence of heart attacks was 2.4% in the calcium takers and 1.6% in the placebo group, a 50% increased risk.

    While there is controversy over use of calcium pills to prevent osteoporosis, researchers note that in calcium-naïve subjects, mineral supplementation demonstrates a consistent adverse effect, namely heart attacks.  Calcium supplementation without accompanying vitamin D increases the relative risk for a heart attack by about 30%.

    Vitamin D is an anti-calcifying agent.  It should accompany all calcium formulations for bone health.  However, vitamin D is often mischaracterized as an inducer of arterial calcification, but only with experimental doses that far exceed human consumption.

    To make matters worse, recommendations by health organizations suggest 700-1200 milligrams of calcium per day.  But that recommendation includes diet + supplements.  Physicians and dietary supplement makers misread these recommendations and mistakenly believe 700-1200 mg represents what should be provided from supplements alone.

    The American diet provides ~600-1200 mg of calcium.  Some Americans consume 800-1200 mg of calcium from their diet and another 1200 mg from supplements, which represents calcium overload.

    This evidence makes calcium pill users and their doctors appear to be mindless fools.

    An exception

    Americans and others living in dairy countries don’t need to rely upon calcium pills.  Their dietary intake is sufficient.  An exception are ~30 million Americans who are lactose intolerant (or A1 intolerant) and avoid calcium-rich foods.  This dairy-avoiding segment of the population may need calcium supplementation.

    Of interest is a recent study that shows bone-hardening bisphosphonate drugs raise vitamin D levels.  Why not just take vitamin D?

    In a stark contrast to the null or negative calcium trials, three different controlled trials show that estrogen supplementation significantly reduces hip, vertebral and all fractures.  Once estrogen was halted the fracture benefit dissipated in these studies.

    Enter phytoestrogens

    This brings this report to the subject of plant estrogens, so-called weak phyto (plant) estrogens, natural molecules that are structurally similar to estrogen, the primary female sex hormone.

    By virtue of their similarity to estrogen, these phytoestrogens bind to estrogen cell surface receptors and thus calm the growth effects of estrogen that are of concern to older women who must avoid cancer, particularly breast and ovarian cancer.

    Phytoestrogens exert both estrogen-like and anti-estrogen effects and can serve as an alternative to estrogen replacement therapy due to their purported ability to reduce bone loss, heart disease, cancer and menopausal symptoms.

    Which prompts the study of resveratrol, a phytoestrogen that exhibits profound bone-maintenance properties.

    Modern medicine is reluctant to conduct human clinical trials with resveratrol.  The vast majority of controlled studies that involve resveratrol are animal studies.

    How resveratrol works

    Oftentimes clinicians are reticent to utilize a phytoestrogen like resveratrol until its underlying mechanisms are known.  But in the instance of resveratrol, its biological bone regenerating mechanisms are known.

    MicroRNA is considered an important controller of bone health.  Resveratrol has been shown to inhibit a microRNA-338-3p.  So it cannot be said underlying mechanisms are not understood. Resveratrol prevents bone loss in rodents whose estrogen-producing ovaries have been surgically removed by inhibiting microRNA-388-3P.

    Resveratrol also exerts a protective effect on osteoporosis via activation of the Siruin1 survival gene.  The Sirtuin1 gene is the master regulator of osteoblasts, cells that rebuild bone. 

    Researchers report that resveratrol, by virtue of its ability to activate the Sirtuin1 survival gene, promotes spontaneous new bone growth (osteogenesis) while it inhibits the development of fat cells (adipogenesis).

    Iron overload is responsible for the progressive aging observed in humans once full growth is achieved in males and cessation of iron-loss due to monthly menstruation ceases in females with the onset of menopause.  Excess iron induces bone loss in animals.  Oral resveratrol prevents iron-associated bone loss in the experimental animal lab.

    Molecular combinations

    Resveratrol in combination with other molecules like quercetin may exhibit superior bone maintenance.

    The combination of resveratrol, inositol and vitamin D, ingredients provided in Longevinex, represent a novel approach to maintaining bone health.


    Resveratrol does not exhibit growth stimulation seen in estrogen-sensitive tissues.  In one study assessing cancer risk, a number of phytoestrogens were tested (genistein from soy, naringenin from grapefruit, coumestrol from clover, and all of them stimulated cell growth except resveratrol.

    While estrogen is an established treatment for osteoporosis it has drawbacks, namely a mild increased risk for cancer and heart disease.  Resveratrol is posed as a safer alternative.

    Resveratrol also exhibits other health benefits typically attributed to estrogen.

    Osteocalcin is a protein/hormone found in bone that plays a role in bone mineralization.   Osteocalcin is responsible for removal of bone whereas osteonectin is responsible to rebuild bone.  The thyroid hormone T3 stimulates osteocalcin and subsequent bone loss.  Resveratrol inhibits T3 stimulation of osteocalcin.

    When compared to other natural molecules in a lab dish study only resveratrol was able to activate osteoblast cells (bone regenerative cells) similar to estrogen

    Men too

    In a human trial, resveratrol has been demonstrated to maintain bone density in menMega-dose resveratrol has been demonstrated to maintain bone in the spine of males.  The use of synthetic resveratrol without accompanying vitamin D is believed to be the reason why mega-dose resveratrol was needed to produce a positive effect in males.  Resveratrol sensitizes the vitamin D cell surface receptor.  Vitamin D serves to aid the absorption of calcium and magnesium.

    Take away lessons:

    1. Doctors, who mostly frown upon use of dietary supplements, uncharacteristically prescribe calcium supplements for their postmenopausal patients without scientific validation.  Ironically, physicians prescribe calcium, which is associated with increased risk for mortal heart attacks and other symptoms.
    2. Age-related bone loss is not due to a lack of calcium requiring supplementation but rather due to a decline in estrogen.  The diet generally provides adequate calcium, particularly in dairy countries (North America, Scandinavia, Ireland, New Zealand).
    3. Age-related bone loss largely occurs in women and is associated with a decline in estrogen production from the ovaries.
    4. Estrogen holds calcium in bone.  Intake of supplemental calcium is akin to pouring calcium into a barrel with a hole in the bottom – it will lead to greater calcium deposition and stiffening of arteries.
    5. Estrogen supplementation or some other similar substitute (i.e. phytoestrogen) is needed to avert fractures with advancing age.
    6. Resveratrol as a phytoestrogen is the most obvious alternative to estrogen replacement or to use simultaneously with estrogen to inhibit its side effects.  Resveratrol does not promote abnormal cell growth as does estrogen.
    7. Combinations of small estrogen-like molecules work better than plain resveratrol at maintaining bone strength.  The concomitant use of vitamin D with resveratrol is suggested.

    This report is a repeat of prior reports, which show resveratrol is vastly underutilized in modern medicine.  Physicians are not familiar with resveratrol.  Patients who inquire of their doctors as to the suitability and safety of using resveratrol to help maintain bone with advancing age are predictably going to be met with unfavorable replies.  ©2017 Bill Sardi,

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