Are Bio-identical hormones safer than non-bio-identical hormones?

Bio-identical-hormones

Are Bio-identical hormones safer than non-bio-identical hormones?

For HRT to be bio-identical, TWO important criteria must BOTH be met:

  • The hormones used must be identical to those found naturally in the body. This includes progesterone, estriol and estradiol (all which occur as such in the body). Non bio-identical hormones include the progestins (eg medroxyprogesterone acetate) and estrogens extracted from horse urine (Equilin).

AND

  • The above hormones by be administered via a non-oral route, to avoid first pass metabolism by the liver (first liver pass metabolism greatly increases blood clotting risk). In nature these hormones are produced by the ovaries and secreted directly into the blood stream, thereby bypassing fist pass liver effects. Bio-identical HRT does the same thing by using the transdermal or injectable route which also bypasses the liver.

Evidence that bio-identical HRT is safer than non bioidentical HRT:

  • As it relates to the two criteria required above for HRT to be bio-identical:
  • The hormones used must be identical to those found naturally in the body. This includes progesterone, estriol and estradiol (all which occur as such in the body). Non bio-identical hormones include medroxyprogesterone acetate and estrogens extracted from horse urine (Equilin):

All non bio-identical progesterone and non-bio-identical estrogen increase the risk of breast and endometrial cancer:

  • International Agency for Research on Cancer (IARC) – Summaries & Evaluations -PROGESTINS (Group 2B) Supplement 7: (1987) (p. 289) – [http://www.inchem.org/documents/iarc/suppl7/progestins.html];
  • J. E. Rossouw et al “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial” in Journal of the American Medical Association (2002) Volume 288, pages 321-333.
  • G. L. Anderson et al “Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial” in Journal of the American Medical Association (2004) Volume 291, pages 1701-1712.
  • C. Straczec, et al “Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration” in Circulation (2005) Volume 112, pages 3495-500).

bio-identical progesterone reduces breast cancer risk, whereas medroxyprogesterone does not:

  • Campagnoli C.; “Pregnancy, progesterone and progestins in relation to breast cancer risk”; J Steroid Biochem Mol Biol. 2005 Dec;97(5):441-50).

Bio-identical Progesterone work differently and more safely in the body than medroxyprogesterone acetate:

  • Simoncini T, Mannella P, Fornari L, Caruso A, Willis MY, Garibaldi S, Baldacci C, Genazzani AR.; “Differential signal transduction of progesterone and medroxyprogesterone acetate in human endothelial cells”.; Endocrinology. 2004 Dec;145(12):5745-56 – ).

Bio-identical estriol binds to the second estrogen receptor ERBeta, which is a tumor suppressing receptor:

  • Bardin A, Boulle N, Lazennec G, Vignon F, Pujol P.; “Loss of ERbeta expression as a common step in estrogen-dependent tumor progression”.; Endocr Relat Cancer. 2004 Sep;11(3):537-51).
  • Unlike the WHI using non-bioidentical HRT which increased cancer, bio-identical estriol metabolism does not result in the formation of large numbers of carcinogenic substances:
  • Lemon HM; “Pathophysiologic consideration in the treatment of menopausal patients with oestrogens; the role of oestriol in the prevention of mammary carcinoma.”; Acta Endocrinol (Copenh); 1980; 223: S17-S27)

Estriol is able to restore normal vaginal cytology at a dose 3-5 times lower than the dose of estriol that causes endometrial hyperplasia. This is in contrast to the other estrogens where the therapeutic dose is similar to the dose that causes hyperplasia:

  • Husin J.; “Cytological Evaluation of the effect of various estrogens given in post menopause.” Acta Cytologica; 1977; 21:225-228.

AND

  • The above hormones by be administered via a non-oral route, to avoid first pass metabolism by the liver which greatly increases blood clotting risk. In nature these hormones are produced by the ovaries and secreted directly into the blood stream, thereby bypassing fist pass liver effects. Bio-identical HRT does the same thing by using the transdermal or injectable route:

That the oral non-bioidentical route, but not the transdermal bio-identical route increases blood clotting risk:

      • Scarabin PY, Oger E, Plu-Bureau G; “EStrogen and ThromboEmbolism Risk Study Group. Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk.”; Lancet. 2003 Aug 9;362(9382):428-32
      • Marianne Canonico et al., “Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women -Impact of the Route of Estrogen Administration and Progestogens: The ESTHER Study”; Circulation Feb 2007;115;840-845 ).

Conventional HRT vs. Bio-Identical HRT (BHRT)

Introduction:

  • “Bioidentical” hormone replacement therapy (BHRT) is a modification of conventional hormone replacement therapy that involves use of supplemental doses of hormones, with 3 important criteria:
  • BHRT has the identical chemical structure to the hormones that exist naturally in the human body, and
  • BHRT is used to replenish levels to physiologically normal concentrations, never exceeding physiological levels, and
  • BHRT is administered via a mode/route of administration that most mimics the body’s natural production (eg given transdermally to avoid metabolic byproducts produced by first pass metabolism to the liver, which occurs only with oral dosage routes, which for example increases the risk of blood clotting

(REFERENCE: Scarabin PY, Oger E, Plu-Bureau G; EStrogen and ThromboEmbolism Risk Study Group. Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet. 2003 Aug 9;362(9382):428-32).

  • The term “bioidentical” is used because the administered hormones although chemically synthesised, are identical to the endogenous hormones of the human body. Estradiol, progesterone, estriol (another natural estrogen) and testosterone are the most common.
  • In contrast, conventional hormone replacement therapy often involves the use of non-bio-identical hormones which have been modified so that their chemical structure is not the same as endogenous human hormones (hormones the body naturally makes), or are extracted from animal which have non-human estrgoens (eg equilin from horses’ urine does not occur in humans naturally). Another example is where a molecule is added to progesterone to make medroxyprogesterone acetate, which makes this form of synthetic progesterone more bioavailable via oral routes, and patentable -but also increases the risk of cancer

(REFERENCE: Campagnoli C.; Pregnancy, progesterone and progestins in relation to breast cancer risk.; J Steroid Biochem Mol Biol. 2005 Dec;97(5):441-50).

Cancer issues: Estriol, Progesterone and Progestins:

All non bio-identical progesterone and non-bio-identical estrogenincrease the risk of breast and endometrial cancer

(REFERENCES: (1) International Agency for Research on Cancer (IARC) – Summaries & Evaluations -PROGESTINS (Group 2B) Supplement 7: (1987) (p. 289) – [http://www.inchem.org/documents/iarc/suppl7/progestins.html]; (2) J. E. Rossouw et al “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial” in Journal of the American Medical Association (2002) Volume 288, pages 321-333. (3) G. L. Anderson et al “Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial” in Journal of the American Medical Association (2004) Volume 291, pages 1701-1712. (4) C. Straczec, et al “Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration” in Circulation (2005) Volume 112, pages 3495-500).

This is in contrast to bio-identical progesterone and bio-identical estriol estrogen which are considered protective against breast cancer:

  • A) Bio-identical progesterone protects against breast cancer, whereas progestins (medroxyprogesterone acetate and 19-nortestosterone-derivatives) increase risk.(REFERENCE: Campagnoli C.; Pregnancy, progesterone and progestins in relation to breast cancer risk.; J Steroid Biochem Mol Biol. 2005 Dec;97(5):441-50).
  • B) Estriol binds to the second estrogen receptor ERBeta, which is a tumor suppressing receptor

(REFERENCE: Bardin A, Boulle N, Lazennec G, Vignon F, Pujol P.; Loss of ERbeta expression as a common step in estrogen-dependent tumor progression.; Endocr Relat Cancer. 2004 Sep;11(3):537-51).

Additionally, one of the leading researchers on estriol, Henry Lemon, MD, of the University of Nebraska postulated that estriol is probably a safer from of estrogen in regard to breast cancer for the following reasons:

  • In vitro, when given with estradiol, estriol accelerates the removal of estradiol bound to protein receptors.
  • Investigators have been able to initiate very little carcinogenesis in animal studies unless large doses (200-500mcg/kg/day) were used on a continuous basis.
  • In animal studies estriol has been found to prevent carcinogen-induced mammary tumours; and
  • Unlike estrone and estradiol, estriol metabolism does not result in the formation of large numbers of carcinogenic substances.
    (REFERENCE: Lemon HM; Pathophysiologic consideration in the treatment of menopausal patients with
    oestrogens; the role of oestriol in the prevention of mammary carcinoma.; Acta Endocrinol (Copenh); 1980;
    223: S17-S27)
  • However, whilst Estriol appears to be safer than estrone and estradiol and, in some situations provides some protection against carcingenesis, other research reports that estriol’s use in breast cancer patients with active disease or in patients with at high risk of breast cancer should be approached with caution. Estriol’s breast cancer benefits seem to occur when intermittent (ie once daily doses) are used in preference continuous dosages (2-3 times daily). More research is needed in this regard, but thus far looks promising.

(REFERENCE: Head K.Estriol: Safety and Efficacy; Alt Med Rev; 1998; 3(2): 101-113).

Method of administration: Oral vs. Transdermal

  • The sex steroid hormones can be administered orally, but when administered in this way most of the hormone is destroyed by the liver soon after entering the body. In the case of progesterone, the resulting metabolic by-products can cause unwanted side-effects. In the case of estrogens, oral administration can alter the production of clotting factors by the liver, increasing the risk of dangerous strokes. For these reasons, topical administration of sex steroid hormones is increasingly popular, since they bypass the liver –mimicking what naturally occurs in the body (this is one of the prerequisites of BHRT). Some hormones have been made available as manufactured transdermal patches, particularly estradiol. Progesterone and estriol are mostly available in the form of topically applied creams made by a trained pharmacist from a compounding pharmacy, preferably incorporated into liposomes to improve bio-availability:
  • Incorporation of the hormones into liposomal gels is the most effective way of ensuring transdermal systemic absorption

(REFERENCES: [1] Kumar R, Katare OP.; Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: a review; AAPS PharmSciTech. 2005 Oct 6;6(2):E298-310 – [2] Willimann HL, Luisi PL. Lecithin organogels as matrix for the transdermal transport of drugs. Biochem Biophys Res Commun. 1991 Jun 28; 177(3):897-900). – see document titled: Pharmacodynamics of Transdermal Delivery for additional information.

Dangers of Conventional, non bio-identical HRT:

  • Bio-identical hormone replacement therapy has received increased attention since the termination of the Women’s Health Initiative hormone replacement therapy clinical trials showed increased risks of breast cancer, stroke and heart disease, using non-bioidentical estrogens and progestins.
    (REFERENCES: (1) J. E. Rossouw et al “Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women’s Health Initiative randomized controlled trial” in Journal of the American Medical Association (2002) Volume 288, pages 321-333. (2) G. L. Anderson et al “Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative randomized controlled trial” in Journal of the American Medical Association (2004) Volume 291, pages 1701-1712. (3) C. Straczec, et al “Prothrombotic mutations, hormone therapy, and venous thromboembolism among postmenopausal women: impact of the route of estrogen administration” in Circulation (2005) Volume 112, pages 3495-500).

SUMMARY: Potential advantages of BHRT over conventional Hormone Replacement Therapy

  • Emphasis on topical administration; avoids problems such as blood clotting that are caused by the rapid metabolism of orally administered hormones

(Scarabin PY, Oger E, Plu-Bureau G; EStrogen and ThromboEmbolism Risk Study Group. Differential association of oral and transdermal oestrogen-replacement therapy with venous thromboembolism risk. Lancet. 2003 Aug 9;362(9382):428-32 – ).

  • Bio-identical Progesterone may work differently and more safely in the body than medroxyprogesterone acetate (a progestin)

(Simoncini T, Mannella P, Fornari L, Caruso A, Willis MY, Garibaldi S, Baldacci C, Genazzani AR.; Differential signal transduction of progesterone and medroxyprogesterone acetate in human endothelial cells.; Endocrinology. 2004 Dec;145(12):5745-56 – ).

  • Progestins, but not bio-identical progesterone, increases risk of breast cancer (Campagnoli C.; Pregnancy, progesterone and progestins in relation to breast cancer risk.; J Steroid Biochem Mol Biol. 2005 Dec;97(5):441-50).
  • Inclusion of estriol may be protective against hormone-induced cancer. Unlike estradiol, estriol binds preferentially to the second estrogen receptor (ERbeta). ERbeta may function as a tumor suppressor

(Bardin A, Boulle N, Lazennec G, Vignon F, Pujol P.; Loss of ERbeta expression as a common step in estrogen-dependent tumor progression.; Endocr Relat Cancer. 2004 Sep;11(3):537-51 – ).

  • Endometrial safety: Estriol is able to restore normal vaginal cytology at a dose 3-5 times lower than the dose of estriol that causes endometrial hyperplasia. This is in contrast to the other estrogens where the therapeutic dose is similar to the dose that causes hyperplasia

([1] Husin J.; Cytological Evaluation of the effect of various estrogens given in post menopause. Acta Cytologica; 1977; 21:225-228. [2] Head K.Estriol: Safety and Efficacy; Alt Med Rev; 1998; 3(2): 101-113 – ).

  • Emphasis on individualized doses rather than “one dose fits all” approach of conventional hormone replacement therapy

(Romero M.; Bioidentical hormone replacement therapy. Customising care for peri-menopausal and menopausal women.; Adv Nurse Pract. 2002 Nov;10(11):47-8, 51-2).

  • Estradiol alone is not adequate (even though some coverts to estriol). This is because doses above 0.25mg daily can raise estradiol to supra-physiological doses, yet not raise estriol enough to improve the estrogen quotient (ratio of Estriol: Estrone+Estradiol), essential for breast cancer protection. Therefore Estriol must be administered in addition.

(Wright, JD.; Bio-Identical Steroid Hormone Replacement Therapy – Selected observations of 23 years of clinical and laboratory practice; 2005: Ann N.Y. Acad. Sci.; 1057: 506-524 – ).

  • Incorporation of the hormones into liposomal gels is the most effective way of ensuring transdermal systemic absorption

([1] Kumar R, Katare OP.; Lecithin organogels as a potential phospholipid-structured system for topical drug delivery: a review; AAPS PharmSciTech. 2005 Oct 6;6(2):E298-310 – [2] Willimann HL, Luisi PL. Lecithin organogels as matrix for the transdermal transport of drugs. Biochem Biophys Res Commun. 1991 Jun 28; 177(3):897-900). – see document titled: Pharmacodynamics of Transdermal Delivery for additional information.

Human hormone replenishment and the necessity for compounding

Hippocratic oath

  • The father of medicine.
  • First do no harm.
  • The body wants to be in a state of wellness.
  • Let thy medicine be thy food, let the food be thy medicine .
  • I will exercise the art of medicine solely for the cure of my patients.
  • I will not carry out studies, neither procedures nor surgery, only for monetary gain.
  • I will care for my patients and their families as I care for me and my family.

Evidence based medicine

  • If only things supported by large placebo controlled studies can be prescribed, perhaps we should stop drinking and prescribing water until it is proven to be safe in a double blind placebo controlled study. would such a study be ethical?
    OF COURSE NOT!
  • Evidence based medicine shouldn’t stop drs from applying their minds.
  • Is it logical to prescribe horse estrogen (equilin) in place of BHRT (human estrogen) because there are large double blind placebo controlled clinical trials on premarin? This is offensive to logic.
  • Where is the science in not being able to check equilin and progestin levels in women post dosing!!
  • One size does not fit all so therefore individualised dosing is required.

How is this for “Evidence” based medicine?

  • Conjugated Estrogens are the number one most prescribed Pharmaceutical Drug (based on the number of prescriptions dispensed in the USA during 1999).
  • Composition of Conjugated Estrogens
  • Estrone (75 – 80%)
    Equilin (6 – 15%)
    17-Alpha-Dihydroequilin
    17 Alpha-Dihydroequilenin
    Estradiol 17-Alpha
    Estradiol 17-Beta
  • Equilenin
    17-Beta-Dihydroequilin
    17-Beta-Dihydroequilenin
    Delta-8,9-Dihydroestrone
  • When last did any doctor check their patients Equilin levels Or 16-Hydroxy-Estrone Levels?

Are all drugs proven safe?

  • An excerpt from the below article.
  • I view Dr. Wright as one of the major pioneers in helping to educate physicians about the natural medicine paradigm. It’s interesting to notice just how ingrained the conventional view on medicine and medical science really is; conventional medicine is said to be backed, and proven by science.
  • But the reality is that only 15 percent of all things done in current medicine have ever been proven by a controlled clinical trial. 15 percent.
  • This shocking fact has been repeatedly confirmed and published by such entities as the Office of Technology Assessment (a branch under a different name of the U.S. Congress), and by Duke University Research Sciences, just to name a couple of the sources.
  • In truth, there’s just as much scientific proof on natural medicine as there is in conventional medicine, but this fact is simply ignored and under reported because techniques such as those of Dr. Wright will not create billions of dollars for the pharmaceutical industry.
  • Hundreds of thousands of patients—perhaps millions—currently benefit from compounded hormone replacement therapy as prescribed by their physicians. For many of these patients, these medications are their only source of relief and health from symptoms of menopause and perimenopause. There is no evidence, clinical or otherwise, to suggest that these women should have their therapies stripped from them.
  • You are probably aware by now that January 2008 FDA made a horrible decision—choosing Wyeth’s wealth over patient health. FDA agreed to support Wyeth in their campaign to end compounded hormone replacement therapy—specifically by starting a crackdown on the use of estriol which FDA claims is illegal.
  • FDA also states that pharmacies must stop making claims of safety and efficacy including the use of the term bio-identical. IACP is unequivocally opposed to FDA’s efforts to restrict the use of estriol and believes the use of the term “bio-identical” is appropriate.
  • In a press conference, FDA admitted there was not a single instance of an adverse event related to estriol that has been reported to FDA.
  • Estriol has a USP monograph. It is recognized by USP. To compound estriol pursuant to a valid prescription is consistent with USP standards (chapters 795 and 1075), the Pharmacy Compounding Accreditation Board’s standards, and state pharmacy law. Congress specifically recognized and approved the use of active ingredients that have a USP monograph as appropriate for use in compounding.
  • There is currently an estriol product in phase III clinical trials for the treatment of Multiple Sclerosis. The safety data thus far has allowed the trials to continue to proceed.
  • Estriol has been used in Asia and Europe for years. Its use is well-supported in medical literature.
  • The use of the term bio-identical is an accurate descriptor of what these estrogens are. FDA-registered manufacturers use the term on their websites to describe FDA-approved estrogen and progesterone products.
  • From both a clinical and legal point of view, the evidence supporting our cause is compelling. FDA is wrong. It is in the best interest of patients to continue to receive the medications they are prescribed.
  • IACP is engaged in a series of additional actions to win this campaign and save BHRT for our patients. We are calling on other pharmacy and healthcare organizations that share our concern to support our cause. We are reviewing potential legal actions and strategies. We called for an immediate meeting with the FDA commissioner’s office. We are reaching out to the media. We are contacting our supporters in Congress. Finally, we are assisting the six IACP members who received warning letters from FDA for using estriol. As in times past, if we all do our part, we will win!

Pharmaceutical industry

  • The legislative/regulatory framework is so heavily biased towards patentable molecules that it is heavily biased against natural medicines and bioequivalent hormones which cannot be patented because they occur naturally in the human body!
  • Why would anyone spend 900million US dollars on a non-patentable product to bring it to market?
  • The presumption that registered drugs are safer is totally ludicrous, anyone remember the drug Vioxx and Prexige ?
  • A registered drug is removed from the market every week and only 15% of drugs have actually been proved safe
  • Drugs are riddled with side effects and cause even deaths.
  • In the USA the prescribing of correct doses of pharmaceuticals is the 3rd to 4th leading cause of death
  • Registration only shows that short term use of a drug is safe
  • Long term safety uses the public as an experiment!
  • In contrast bioidentical hormones occur naturally in the human body and in physiological doses have only benefit!

Bio-identical Hormones

  • The physician is only the servant of nature, not her master. Therefore it behooves medicine to follow the will of nature.
  • PARACELSUS

Recent opinions voiced at the menopause conference October 2007

  • Opinion 1: Compounded hormones are not regulated
  • Fact: compounded hormones are regulated in terms of section 14(4) of the medicines act 101. Furthermore, according to the pharmacy act, compounding is one of the unique activities specially relating to the pharmacist’s profession. Removing compounding from pharmacists would render them mere dispensors.
  • Opinion 2: They are prescribed by non-medical practitioners
  • Fact: compounded hormones have a schedule status, eg estradiol, estriol are schedule 4 ; testosterone is schedule 5. These schedules are observed in pharmacies. You shouldn’t legally be able to get them without a doctors prescription
  • Opinion 3: Compounded hormones are “not well absorbed”
  • Fact: The compounding pharmacy of SA uses the most advanced transdermal delivery known as a pluronic lecithin gel. Retrospective data from doctors proves improvement of symptoms and lab test changes on hormone levels
  • Opinion 4: “purity, potency, efficacy are not monitored”
  • Fact: Indeed the above is monitored. We randomly send products for quantitative analysis to verify label claim. Efficacy and safety is monitored by the patient’s doctors
  • Opinion 5: “bioidentical hormones are not safer than the alternatives” In fact at recent menopause conference it was stated that they are more dangerous!
  • Fact: A better name for these hormones is human hormones, they occur naturally in your body. They are not horse hormones and not progestins. Humans need human hormones. We do not need mega doses of non-human hormones.
  • Opinion 6: “ It is impossible to balance one’s hormones”
  • Opinion 7: Customization and individualisation of an individuals hormones is not possible
  • Fact: Through lab testing including serum, 24 hr urine, saliva and bloodspot testing, as well as symptomatology improvement it is indeed possible to balance and optimize an individual’s hormones. In antiaging medicine we do not adopt a one size fits all approach like with conventional hrt. We individualize doses and this is why compounding of the right dose for an individual is essential and a necessity!!
  • Opinion 8: Saliva testing is a lot of rubbish
  • Fact: NASA use salivary cortisol to assess the stress levels of astronauts.
  • Extensive work has been done on saliva testing to show that it does reflect tissue levels of hormones
  • Does transdermal progesterone protect the endometrium, with the evidence below

Progesterone

  • Fertility and sterility Vol 70, no 1 , jan 2003 Topical progesterone cream has an antiproliferative effect on estrogen-stimulated endometrium
  • 37 women studied, 98% completed the study, minimal vaginal spotting occurred in 6 women.
  • Endometrial histologic changes confirmed an antiproliferative effect of transdermal progesterone.
  • Doses used were a 1.5% and 4% cream

Progesterone effects not seen with Progestins

  • Natural progesterone helps balance estrogen
  • Leaves your body quickly (unlike progestins)
  • Helps you sleep
  • Natural calming effect
  • Lowers high blood pressure
  • Helps your body use and eliminate fats
  • Lowers cholesterol
  • Protects against breast cancer
  • Increases scalp hair
  • Normalises libido
  • Helps balance fluids in the cells
  • Blood vessel dilation
  • Antiproliferative effect
  • Increases metabolic rate
  • Natural diuretic, natural antidepressant

Common effects of Progesterone and Progestins

  • Builds bone
  • Helps thyroid hormone function
  • Protects against fibrocystic breast disease
  • Protects against endometrial cancer
  • Normalises zinc and copper levels

Progesterone

  • Cancer research 62,881-886,feb 1,2002 Progesterone inhibits human endometrial cancer cell growth and invasiveness: down regulation of cellular adhesion molecules through progesterone B receptors
  • Progesterone controls cell proliferation and differentiation in the female reproductive tract. Acts on progesterone A and B receptors
  • Loss of PRB has recently been linked to poorly differentiated endometrial cancer
  • Cancer research 62,881-886,feb1 2002
  • Progesterone caused time-dependant inhibition of cell cycle
  • Progesterone inhibited endometrial cancer cell division
  • Progesterone induced a secretory phenotype through PRB
  • Progesterone induced replicative senescence through PRA
  • Progesterone and growth factor deprivation induced apoptosis
  • Progesterone inhibited the cell cycle by upregulating cdk inhibitors p21 and p27
  • Progesterone downregulated the expression of cellular adhesion molecules
  • Menopause: The journal of the north american menopause society vol 12 no 2 p 232-237 Percutaneous administration of progesterone :blood levels and endometrial protection.
  • Antiproliferative effects on the endometrium are seen with progesterone creams even at low circulationg blood levels.
  • Despite the low serum levels, saliva testing confirms high levels reflecting high tissue levels.
  • Progesterone gels are watersoluble and enters the microcirculation more rapidly elevating serum progesterone levels .

Progesterone creams and Endometrium

  • Serum progesterone levels greater than 5ng/ml to inhibit endometrial mitosis and to induce a secretory change.
  • Although serum progesterone levels<3.5ng/ml are generally considered too low to cause a secretory endometrium, 2 reports contradict this generality.
  • Leonetti et al fertil steril 2003;79:221-222 reported decreased endometrial proliferative effects despite low serum levels and varying values between people
  • Supported by landes et al obstet gynecol 2003;101(suppl 1) :S6
  • In general the most significant effects are found after 4 to 6 weeks usage.
  • It seems length of treatment rather than dose is what is important
  • Base decisions on endometrial biopsies rather than blood levels
  • Remember %progesterone cream can be increased if needed (for example a 5 or 10% even if required)

Progesterone

  • American Journal of obstetrics and gynecology volume 180,issue 6 june 1999 percutaneous absorption of progesterone in postmenopausal women treated with transdermal estrogen
  • An appropriate increase in progesterone concentration occurred after 4 weeks
  • After 2 weeks of percutaneous dosing progesterone concentrations were sustained for at least 8 hours and were consistent within a given person
  • Significant elevation of serum progesterone occurred in all women studied
  • The percutaneous application of progesterone cream appears to be a safe and effective route of administration
  • Oral micronized progesterone at a dose of 100mg given 25 days of the month protected the endometrium from proliferation and induced amenorrhea in >90% of women (gillet jy, maturitas 1994;19:103-15.
  • Journal of the american college of cardiology vol 36,no7 2000 Natural progesterone, but NOT medroxyprogesterone, enhances the beneficial effect of estrogen on exercise induced myocardial ischemia in postmenopausal women.
  • Progestins cause coronary vasospasm, unlike progesterone.

Progestins

  • Side effects of progestins not seen with natural progesterone include: increase in appetite, weight gain, fluid retention, irritability, depression, headache, decrease in energy, bloating, breast tenderness, decreases sexual interest, rash,acne, hair loss, nausea, insomnia, breakthrough bleeding,spotting, interferes with the body’s own production of progesterone,does not help balance estrogen, remains longer in your body, coronary artery spasm, stops the protective effects estrogen has on the heart, attaches to other receptors in your body as well, cannot help make estrogen and testosterone,increases ldl,decreases hdl,protects only the uterus from cancer, counteracts the positive effects of estrogen on serotonin.

Progesterone

  • European Journal of neuroscience, vol 23,p43-54,2006 Anti-apoptotic effects of allopregnanolone on P19 neurons.
  • Progesterone and its metabolites are potent modulators of GABA A receptor function contributing to receptor plasticity and modulating the expression of its subunits.
  • Neurosteroids like progesterone can act as survival factors by interfering with the mitochondrial apoptotic pathway.

Bioidentical Hormone Therapy: A Review of the Evidence

MICHAEL CIRIGLIANO, M.D., F.A.C.P.
CRITICAL POINTS IN DISPUTE

The purpose of this review is to examine whether there is sufficient clinical evidence to support claims of greater efficacy and safety for compounded BHTs compared with CHTs. (Page 601-Last Paragraph)

  • Response: The central question to this study is loaded and is in fact a red herring. “Compounding pharmacy is the long-standing process of mixing drugs by a pharmacist or physician to fit the unique needs of a patient.” (ref: Wikiepedia) The very nature of compounding requires by definition the unique needs of a patient. You cannot have large numbers of unique patients and unique medicines in one trial. The author is pulling a fast one to confuse doctors. He is constantly referring to compounded BHT not BHT. Of course there will not be any evidence in support of this. Let him review the studies of Non-compounded ie registered bio-identicals and the review may be different.
  • http://en.wikipedia.org/wiki/Compounding

Many advocates of compounded BHTs customize prescriptions based on saliva testa or blood sera levels in direct contradiction to evidence based guidelines, which support tailoring HT individually according to symptoms(Page 600-Abstract-7th Last Line)

  • Response: Writers opinion. No evidence for this. All doctors in SA use symptomatic evaluation COMBINED with blood testing

The addition of further estrogen metabolites (estrone and estriol) in an ad hoc compounded mixture containing estradiol, based on saliva or sera estrogen levels, in an effort to provide a theoretical ideal ratio seems futile because the exogenous estradiol and estrone fractions are subject to metabolism at different rates.32,129 It would make more sense to provide sufficient amounts of estradiol alone and then allow the woman’s own metabolism to provide for the other estrogens. (Page 617-Abstract-127th Line)

  • Response: This is like saying let Women eat a sufficient amount of Cholesterol or take Pregnenolone and allow the womens own metabolism (ie steroid pathway) to provide for the other steroid hormones.

(Suzanne) Somers’ newbook, Ageless: The Naked Truth About Bioidentical Hormones,70 which reached national best-seller lists, maintains that customized, compounded BHTs can also reverse the aging process and keep people mentally sharp, physically fit, and sexually active. None of these statements has been clinically proven,………………… (Page 6111-3rd Last Line)

  • Response:
  • Aging Process:
  • Estrogens (specifically topically applied 0.01% Estradiol or 0.3% Estriol (oral Estrogens replacement therapy may also be effective) may retard and reverse some aspects of the Aging Process in the Skin.

– Brincat, M. P. Hormone replacement therapy and the skin. Maturitas. 35(2):102-117, 2000.

– Schmidt, J. B., et al. Treatment of skin aging with topical estrogens. International Journal of Dermatology. 9(35):669-674. 1996.

Mental Sharpness:

  • Estrogen replacement therapy has been demonstrated to improve short-term memory and long-term memory in young women. In older healthy women estrogen replacement therapy appears to improve some aspects of cognition including immediate and delayed recall, but not spatial/visual memory.
    Dubal, D. B., et al. Estradiol: a protective and trophic factor in the brain. Alzheimer’s Disease Review. 4:1-9, 1999.
  • DHEA (Dehydroepiandrosterone) may enhance Memory and may inhibit the Memory-impairing effects of Alcohol (ethanol).
    Alhaj, H. A., et al. Effects of DHEA administration on episodic memory, cortisol and mood in healthy young men: a double-blind, placebo-controlled study. Psychopharmacology. 2005.Psychobiology Research Group, School of Neurology, Neurobiology and Psychiatry, University of Newcastle upon Tyne, Newcastle upon Tyne, UK.
  • 7-Keto DHEA may improve Memory (in some cases to a greater extent than regular DHEA).
    Shi, J., et al. The effect of 7-oxo-DHEA acetate on memory in young and old C57BL/6 mice. Steroids. 65(3):124-129, 2000.
  • Optimal Testosterone levels enhance Memory (and Testosterone replacement therapy may further enhance Memory)
    Gouchie, C., et al. The relationship between testosterone levels and cognitive ability patterns. Psychoneuroloendocrinology. 16(4):323-334, 1991.

Physical fitness:

  • DHEA (Dehydroepiandrosterone) may increase Stamina.
    Johannsson, G., et al. Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. Journal of Clinical Endocrinology & Metabolism. 87(5):2046-2052, 2002.

Sexual Activity:

  • Supplemental DHEA (Dehydroepiandrosterone) (25 – 50 mg per day) may increase Sexual Desire (especially in elderly women) – this effect most likely occurs as a result of DHEA stimulating Testosterone production. DHEA may also increase Sexual Desire in men.
    1. Arlt, W., et al. Dehydroepiandrosterone replacement in women with adrenal insufficiency. New England Journal of Medicine. 341(14):1013-1020, 1999.
    Department of Endocrinology, Medical University Hospital, Wuerzburg, Germany.
    2. Baulieu, E. E., et al. Dehydroepiandrosterone (DHEA), DHEA sulfate and the aging: contribution of the DHEAge Study to a sociobiomedical issue. Proceedings of the National Academy of Sciences, USA. 97(8):4279-4284, 2000.
    3. Hackbert, L., et al. Acute dehydroepiandrosterone (DHEA) effects on sexual arousal in postmenopausal women Journal of Women’s Health and Gender-Based Medicine. 11(2):155-162, 2002. Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, USA.
    4. Johannsson, G., et al. Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial. Journal of Clinical Endocrinology & Metabolism. 87(5):2046-2052, 2002.
  • Testosterone may increase Sexual Desire in both males and females.
    • Adamkiewicz, M., et al. [no title translated]. Pol Arch Med Wewn. 100(3):212-221, 1998.
    • Ahmed, S. R., et al. Transdermal testosterone therapy in the treatment of male hypogonadism. J Clin Endocrinol Metab. 66(3):546-551, 1988.
    • Alexander, G. M., et al. The association between testosterone, sexual arousal, and selective attention for erotic stimuli in men. Horm Behav. 25(3):367-381, 1991.
    • Arver, S., et al. Improvement of sexual function in testosterone deficient men treated for 1 year with a permeation enhanced testosterone transdermal system. J Urol. 155(5):1604-1608, 1996.
    • Davidson J. M., et al. Effects of androgen on sexual behavior in hypogonadal men. J Clin Endocrinol Metab. 48(6):955-958, 1979.
    • Davidson, J. M., et al. Hormonal changes and sexual function in aging men. J Clin Endo Metab. 57(1):71-79, 1983.
    • Kwan, M., et al. The nature of androgen action on male sexuality: A combined laboratory self-report study on hypogonadal men. Journal of Clinical Endocrinology and Metabolism. 57(3):557–562, 1982.
    • O’Carroll, R., et al. Testosterone therapy for low sexual interest and erectile dysfunction in men: a controlled study. British Journal of Psychiatry. 145:146–151, 1984.
    • Persky, H., et al. The relation of plasma androgen levels to sexual behaviors and attitudes of women. Psychosom Med. 44(4):305-319, 1982.
    • Schiavi, R. C., et al. Pituitary-gonadal function during sleep in men with hypoactive sexual desire and in normal controls. Psychosom Med. 50(3):304-318, 1988.
    • Shifren, J., et al. New England Journal of Medicine. 343:682-688, 2000.
    • Wang, C., et al. Transdermal testosterone gel improves sexual function, mood, muscle strength and body composition parameters in hypogonadal men. Testosterone gel study group. J Clin Endocrinol Metab. 85(8):2839-2853, 2000.

Trial results

  • WHI & Million women study have demonstrated once again that replacing human molecular substance with inexact molecular copies has undesirable consequences.
  • Makes better sense to copy nature, using exact molecular copies of hormones.
  • Copy nature including quantities, routes of administration, and timing of administration

Estradiol: Appropriate dose and metabolism to Estrone

  • Do not exceed physiological quantities of any bioidentical hormone. Follow up testing is always done to ascertain this goal.
  • Good values to aim for would be the physiological range found in young, healthy, cycling women
  • Study (stehman-breen et al) confirms that urinary excretion of estrone (5-10xnormal) is frequently too high with oral doses of estradiol 1-2mg /d. Retrospective studies associate overdosage of oral estradiol to increased risk of breast cancer
  • Tri-e (0.25mg estradiol,0.25mg estriol,2mg estriol) and bi-e (0.25mg estrone, 2-2.25mg estriol) studies have shown both blood and urine doses within physiological range

Lab testing

  • The use of nonhuman pseudohormones automatically precludes post-treatment lab testing since there are no normal lab values for equilin or medroxyprogesterone.
  • Compare thyroxine or tri-iodothyronine. These are bioidentical and lab testing can be done to ensure correct dosage and patient safety

Estrogens

  • Bioidentical combinations include triple estrogen (estrone 10%, estriol 80%,estradiol 10% for example. Bi-est would include for example estradiol 10% -20% and estriol 80-90%. With compounding it is easy to increase the estradiol component to 40 or 50% for example.
  • Even in healthy non-pregnant women estriol is present in higher concentrations than the other two estrogens. Nature must have a reason for having estriol and we should remember to copy nature as far as possible, including timing and route of administration

Route of administration of Estrogen Bioavailablity

  • Nature introduces estrogens and other ovarial steroids into the circulation via the pelvic plexus of veins, carries them to the heart, circulates them through the lungs, then back to the heart again and then to all parts of the body including the liver. It is very clear that nature does not introduce the hormones into the portalvein and directly to the liver.
  • Oral estrogen has a first bypass effect by going to the liver first
  • Therefore replace estrogen and other steroid hormones via the skin!

Route of administration and Bioavailability

  • Intravaginal application of the transdermal hormones is infact the closest to nature since they are then introduced into the pelvic venous plexus
  • Intravaginal and transdermal estrogen is absorbed, metabolized and excreted somewhat differently than orally administered estrogen even if doses are the same

What if no symptom improvement using transdermal bioequivalents

  • These women have often used non-bioidenticals like premarin in the past
  • Usually hyperexcrete the estrogens
  • Estrogen is metabolised by cytochrome P450 and other cytochrome enzymes. Non-responders tend to have upregulated cytochrome enzymes that may be downregulated to normal function.
  • Cobalt can be used to downregulate an overactive cytochrome P450

Iodine and iodide

  • Accumulating research has shown estriol in the presence of more pro-carcinogenic estrogens to become anticarcinogenic
  • Gynecologist/oncologist Henry Lemon MD argues that the relative proportions of each of the estrogen hormones is important. The estrogen quotient : E3/E2+E1. A higher estrogen quotient equates to a lower risk of breast cancer
  • Iodine and iodide stimulates the metabolism pathway to estriol, increasing the estrogen quotient

Functions of Estriol

  • Estriol improves menopausal symptoms including hot flashes,insomnia and vaginal dryness
  • Helps your gut maintain good bacteria (lactobacilli) and helps reduce pathogenic bacteria
  • Estriol benefits the vaginal lining
  • Increases hdl,decreases ldl cholesterol
  • Restores the proper ph of the vagina and helps prevent urinary tract infections
  • Has been used to treat breast cancer
  • Blocks estrone by occupying the estrogen receptor site on breast cells

Estriol

  • Hum Reprod 2000 May; 15(5):1028-36 Safety and efficacy of estriol for symptoms of natural or surgically induced menopause.
  • Estriol proven to be safe and effective in symptom relief. Endometrial biopsy and breast evaluation were normal after 12 months, blood pressure dropped, estriol had no significant effect on lipids except for triglycerides
  • Maturitas 2002 Jun 25;42(2):149-156 The effects of estriol on the endometrium in postmenopausal women.
  • No statistically significant differences were found on endometrial thickness and histology
  • Maturitas 1981 Dec;3(3-4):321-7 Endocrinological and clinical investigations in post-menopausal women following administration of vaginal cream containing estriol. Clinical effect was excellent and no untoward effects were reported
  • Maturitas 2000 oct 31;36(3):217-22 Comparison of the long term effects of oral estriol with the effects of conjugated estrogen on serum lipid profile in early menopausal women.
  • estriol did not induce hypertriglyceridaemia and prevents a postmenopausal rise in total cholesterol.
  • estriol may be a safe alternative for women with high triglycerides, and in women who are reluctant to continue conventional hrt because of uterine bleeding
  • Arch Gynecol Obstet 1992;251(3):115-120 effects of protracted administration of estriol on the lower genitourinary tract in postmenopausal women. The risk of estriol treatment was insignificant
  • Arch Gynecol obstet 1993;253(2):71-74 When applied to facial skin, does estrogen ointment have systemic effects? Serum hormone levels and the appearance of vaginal smears showed no significant change during treatment
  • J gerontol A biol Sci Med sci 2000 Apr;55(4): B 183-90;discussion B191-3 Estriol replacement improves endothelial function and bone mineral density (by inhibiting bone resorption) in very elderly women
  • E3 may be useful for use in hrt in elderly women
  • Orv Hetil 1995 Feb 12;136(7):343-345 Treatment of climacteric urogenital disorders with an estriol-containing ointment
  • Vaginal burning,dryness,urinary dysfunctions,dyspareunia,itching all ceased.
  • E3 is suitable for treatment of chronic vaginitis and cystitis
  • Acta Endocrinol Suppl (copenh) 1980;223:17-27 Pathophysiologic considerations in the treatment of menopausal patients with estrogens;the role of estriol in the prevention of mammary carcinoma.
  • The protective effects was specific for mammary carcinomas.
  • Clinical experience thus far with estriol therapy has indicated little hazard of cancer development
  • J Steroid Biochem 1984Apr;20(4B):959-62 Estriol production and metabolism in normal women
  • Estriol circulates at low but relatively steady levels in the blood. In some women estriol appears to be secreted by the ovary, especially in the luteal phase
  • BJOG 2000 Aug;107(8):1029-34 Estradiol-releasing vaginal ring versus vaginal pessaries in the treatment of bothersome lower urinary tract symptoms.
  • Low dose vaginally administered estradiol and estriol are equally efficacious in alleviating lower urinary tract symptoms.
  • The form of administration of the vaginal ring, seems to be more acceptable than estriol pessaries
  • Mol Endocrinol 1997 Nov;11(12):1868-78 Molecular and kinetic basis for the mixed agonist/antagonist activity of estriol.
  • Estriol is a weak estrogen, resulting from impaired hER (human estrogen receptor)-ERE (ligand response element)
  • Anti-estrogenic activity occurs in a dose dependant fashion, where it reduces estradiol dependant transcription. Estradiol binding to receptor is also decreased
  • Estriol is hypothesized then to oppose carcinogenic effects of estradiol
  • Ann Chir Gynaecol Suppl 1987;202:39-41 Local estriol treatment improves the structure of elastic fibers in the skin of postmenopausal women
  • The elastic fibers in the papillary dermis were thickened, better orientated and increased in number in half of these patients
  • JAMA 1978 Apr 21;239(16):1638-41 Estriol in the management of menopoause
  • Clinical effectiveness was related to dose (2-8mg/d po)
  • Estriol 8mg failed to induce endometrial proliferation
  • Improves vasomotor instability and improves vaginal maturation
  • Maturitas 2001 Sep28;39(3):253-7 Short term oral estriol treatment restores normal premenopausal vaginal flora to elderly women
  • Estriol is highly effective for the treatment of atrophic vaginitis

Correcting misconceptions about compounding bioidentical hormones

  • Prescriptions are prepared by compounding pharmacies
  • Provides individualized and customized therapy that does not meet the definition of manufacturing as described by state boards of pharmacy, FDA and the supreme court
  • Compounding is a profession of pharmacy that HAS ALWAYS been REGULATED by individual state boards of pharmacy
  • Compounded hormones must be prescribed by a physician. The decision to prescribe is a professional judgement made in the interest of the patient
  • One of the foremost references on BHRT is the textbook The clinical Gynecologic Endocrinology and Infertility by speroff and fritz. Failure of commercial products to provide the benefits of endogenous estradiol for example should not be confused with the literature that supports exogenous use of low dose bioidentical estrogen
  • Progesterone has clear advantages over progestins (already discussed)
  • Essential to understand that progesterone protects against breast cancer, progestins increase the risk for breast cancer.

Compounding

  • Conjugated estrogens entered the market in 1943.
  • Due to massive promotional campaigns over the years,non human and non-bioidentical hormones assumed a major share of the market place
  • BHRT did not compete with the highly marketed,patented, nonhuman hormones
  • During the 1980s compounding began making its way back into mainstream healthcare.
  • Insulin was once extracted from pigs and cows
  • Thyroid supplements were originally obtained from pigs.
  • However when human insulin,thyroid hormones became available these were preferred.
  • There is still a pharmaceutical industry driven support for legislation that would control and minimize pharmacy compounding. As an important part of today’s health care, compounding supplies IV admixtures, parenteral nutrition,pediatric preparations, pain management medications.
  • THERE SHOULD BE NO PLACE FOR NON-BIOIDENTICAL HORMONES!!

Questions about efficacy

  • These should be laid to rest because compounded hormones are bioidentical and essential to maintaining good health.
  • Many substances in the human body (like water,electrolytes,thyroid hormones, pancreatic enzymes and insulin are used therapeutically to replace deficiencies.
  • So it should be with all hormones, BIOIDENTICALLY

Pharmaceutical industry

  • Promotes its products and discourages compounding by disseminated misinformation and biased views
  • Pharmacists will continue to compound and meet the needs of patients and physicians
  • The political skirmish between bigpharma and compounding pharmacists will continue for years

Hormone heresy

  • Extracted from nexus magazine, volume 3,nr 4 june1996
  • Women are misinformed about their hormones, to the detriment of their health, while drug companies reap huge profits at their expense.
  • Women are big business to the medical and pharmaceutical interests.
  • There has infact never been any valid scientific proof that the pill is safe, nor for that matter, that any of the other forms of contraception presently available are safe.

Estrogen dominance

  • Or Progesterone deficiency
  • Progesterone stimulates osteoblastic activity in bone
  • Stress and a bad diet can result in low progesterone and anovulatory cycles
  • Environmental : petrochemicals in the air, food and water. Examples are pesticides and herbicides (DDT, dieldrin,heptachlor,etc) as well as plastics and PCBs
  • These xeno-estrogens are not biodegradable and highly fat soluble and can lead to estrogen dominance
  • Supplementation with progesterone can help alleviate estrogen dominance
  • Should hysterectomized women take progesterone if they are deficient: ABSOLUTELY!!!!

Effects of estrogen dominance

  • When estrogen is not balanced by progesterone it can cause weight gain, headaches, bad temper, chronic fatigue and loss of interest in sex (PMS symptoms!).
  • Encourages the development of breastcancer due to estrogen’s proliferative effects. Can also cause fibrocystic disease of the breasts. Natural progesterone can alleviate this.
  • Decreased progesterone results in a decrease in the rate of bone synthesis, this is the prime cause of osteoporosis
    Fibroids. Fibroids often get smaller in the menopause. Using natural progesterone will also cause fibroid atrophy
  • Menstruation becomes irregular.
  • Endometrial cancer develops where there is estrogen dominance or unopposed estrogen.
  • Waterlogging of cells and an increase in intracellular sodium, high blood pressure.
  • Increased risk of stroke and heart disease.

Anti-aging benefits of natural progesterone

  • Progesterone is the precursor of adrenal corticosteroids. Without adequate progesterone,cortisone synthesis is impaired and the body turns to alternate pathways having masculinizing results like long facial hairs, and thinning of scalp hair.
  • Perimenopausal women suffering with hypothyroidism symptoms such as fatigue,lack of energy, intolerance to cold, could actually be suffering from unrecognised estrogen dominance, and would benefit from progesterone.
  • Progesterone is a natural diuretic and antihypertensive.
  • Natural progesterone helps stabilize homeostatic control of glucose when combined with estrogen.
  • Transdermal progesterone is a skin moisturizer which restores skin hydration.
  • Progesterone keeps brain cells healthy. Premature senility can result from progesterone deficiency.
  • Progesterone is needed for the development of the myelin sheath which protects the nerve cells.
  • Progesterone promotes an enhanced sense of emotional well being and psychological self-sufficiency.
  • Progesterone enhances libido.

Bioidentical Hormones

  • If it is not bio-identical do not prescribe it!

Are You A Ticking Time Bomb?

ticking-time-bomb

Are You A Ticking Time Bomb?

As a specialist physician in private practice I have done many insurance medicals to declare people “medically fit and healthy. ” It is quite alarming that the cardiac assessmant required for these insurance medicals is a fasting lipogram, glucose and a stress ecg. First of all it is inflamed, oxidized cholesterol that is linked to coronary artery disease and not just cholesterol per se. Secondly a stress ecg is not the best test to assess the state of coronary artery disease since the test is frequently negative whilst coronary artery disease is clearly apparent on say ct scanning of the coronaries. Often (in women in particular) the stress ecg can be falsely positive as well. Thirdly there is a much bigger picture to the prevention of coronary artery disease than merely lowering cholesterol.

Opposite to common thought that cholesterol is “bad”, people do need cholesterol for normal bodily functioning. Cholesterol is the precursor to vitamin D, steroid hormones (such as estrogen, progesterone, testosterone, dhea, pregnenolone and cortisol), and the bile acids required for digestion. Cholesterol is also required to form the membrane around cells and for regeneration of damaged endothelial cells.

The main sources of cholesterol are liver production (about 800mg a day). Main dietary sources include meat, cheese, milk and eggs. Cholesterol is transported in the blood by lipoproteins. A healthy cell cannot be overfilled with cholesterol unless the cholesterol is oxidized and enters an already inflamed arterial tissue. Cholesterol is in itself not the culprit here. Nature wouldn’t give you a system designed to kill you. The issue is inability to process cholesterol, inflammation and oxidative stress.

The body’s antioxidant system as well as antioxidant supplements and natural anti-inflammatories safeguard against cholesterol deposition in the blood vessel walls resulting in atherosclerosis (blood vessel disease resulting in heart disease, stroke and peripheral vascular disease). The reverse cholesterol transport system that removes cholesterol from one’s arteries requires phosphatidylcholine (PC) and LCAT (lecithin cholesterol acyl transferase). LCAT, an enzyme removes a fatty acid particle from PC and binds it to cholesterol producing an ester. HDL, a circulating “good” cholesterol transports this ester back to the liver.

So Good cholesterol includes:

a) HDL

b) Non-oxidized LDL (essential for normal bodily function)

Bad cholesterol:

a) Oxidized LDL…. This is the cholesterol that leads to blood vessel disease. Deposition in blood vessel walls lead to foam cell formation, plaque formation, blood clotting.

b) lipoprotein (a)…. This is a cholesterol molecule attached to a protein apolipoprotein (a). This molecule has repair function to the arterial wall, however too much of it (usually genetic) promotes formation of blood clots and build up of plaque. This narrows the blood vessel and worsens symptoms.

It is also important to remember that one can check the degree of inflammation in the body by doing a test called hscrp (highly sensitive crp). A value of less than 1 is normal. Increasing values lead to increases in heart and blood vessel diseases.

If you have a high hscrp natural anti-iflammatories like omega 3 fishoil and curcumin are ideal supplements to lower your risk of cholesterol being oxidized and inflamed in blood vessel walls.

High blood pressure, elevated LDL and triglycerides, low hdl, cigarette smoking, elevated LDL and triglycerides, low HDL, diabetes, obesity, and lack of exercise contribute to endothelial dysfunction and the subsequent development of atherosclerosis. 15-25.

Additional endothelial-damaging factors include excess levels of glucose, insulin, iron, homocysteine, fibrinogen, and C-reactive protein, as well as low HDL and free testosterone (in men). 3, 9, 10, 24, 26-28.

Homocysteine is particularly dangerous because it can induce the initial injury to the endothelium. Homocysteine then facilitates oxidation of the fat/LDL that accumulates beneath the damaged endothelium, and finally contributes to the abnormal accumulation of blood components around the atherosclerotic lesion. 29

Fibrinogen is a clotting factor that accumulates at the site of the endothelial lesion. Fibrinogen may contribute to plaque buildup or participate in blood clot-induced blockage of an artery after an unstable atherosclerotic plaque ruptures. 30

Glucose at even high-normal levels may accelerate the glycation process that causes arterial stiffening, while high-normal fasting insulin inflicts direct damage to the endothelium. 31-36

High levels of iron promote LDL oxidation in the damaged endothelium, while low levels of testosterone appear to interfere with normal endothelial function. 9, 11, 14

C-reactive protein is not only an inflammatory marker, but also directly damages the endothelium. Chronic inflammation, as evidenced by persistent high levels of C-reactive protein, creates initial injuries to the endothelium and also accelerates the progression of existing atherosclerotic lesions. 3, 27

In response to numerous published studies, health-conscious people are altering their diets, taking drugs, hormones, and dietary supplements, and trying to exercise regularly in order to reduce these atherosclerosis risk factors. However, these efforts alone cannot be completely successful because age itself is a major risk factor for atherosclerosis.

Atherosclerotic risk conferred by age is attributable in large measure to pathological endothelial dysfunction. 37, 38 As noted earlier, endothelial dysfunction is not synonymous with atherosclerosis, but the two processes are increasingly intertwined with advancing age.

ENDOTHELIAL DYSFUNCTION MARKERS:

1. VEGF (Vascular endothelial growth factor)

2. ADMA (Asymmetric dimethylarginine)

3. VCAM-1 (vascular cell adhesion molecule-s)

4. NOS (Nitric oxide synthase)

ADMA is involved in the pathogenesis of hypertension and atherosclerosis through its inhibition of the formation of the endogenous vasculoprotective molecule, nitric oxide (NO). Determination of ADMA can thus help to predict both the likelihood of developing cardiovascular diseaseand its prognosis. A new competitive ELISA test for ADMA is a useful and fully validated tool suitable for routine laboratory use.
Availalble tests to detect endothelial dysfunction in south Africa include:

a) hsCRP

b) Von Willebrand Factor (WF)

c) PAI-1 (Plasminogen activator inhibitor-1)

d) FDP (Fibrinogen degradation products) – as D-dimer

e) NT-proBNP

f) Homocysteine

g) Active renin

h) Lipids (lipogram) and lipoproteins

i) ACE (angiotensin converting enzyme)

An article published online on October 21, 2008 in the journal Nutrition & Metabolism reported the discovery of Italian researchers of an association between decreased plasma levels of several antioxidants and early carotid atherosclerotic lesions in asymptomatic middle-aged individuals.

“Atherosclerosis remains clinically mute for a long time and frequently manifests itself with an acute cardiovascular event; therefore, the possibility of detecting the disease in a subclinical phase and reducing or reversing its progression is an issue of relevance, ” the authors write. “Antioxidants, which may inhibit lipid peroxidation, could play an important protective role against the formation of simple and complex atherosclerotic lesions, which progressively protrude into the arterial lumen, causing stenosis or occlusion. In particular, increased carotid intima-media thickness represents an early phase of the atherosclerotic process and is widely used as a marker of subclinical atherosclerosis which correlates with established coronary heart disease. ”

Two hundred twenty men and women between the ages of 45 and 65 without history of transient ischemic attack, stroke, or other conditions related to carotid artery disease were enrolled at the San Camillo de Lellis Hospital, in Manfredonia, Italy. Participants underwent ultrasonographic evaluation of the extracranial carotid arteries, and blood samples were analyzed for lipids, C-reactive protein and other factors, in addition to plasma levels of vitamin A, vitamin E, beta-carotene and lycopene.

One hundred twenty-five participants were found to have carotid atherosclerosis as determined by carotid intima-media thickness of 0. 8 millimeters or more. Body mass index, plasma hemoglobin, and high-density lipoprotein cholesterol were marginally higher among those diagnosed with atherosclerosis, and all of the nutrients measured were significantly reduced. Vitamin A, vitamin E, and lycopene levels were decreased by 50 percent or more among those with atherosclerosis compared with participants who were not diagnosed with the condition, and beta-carotene levels were less than a third of those without atherosclerosis.

Oxidative stress resulting from the oxidation of low-density lipoprotein (LDL) cholesterol in the wall of the artery results in inflammation which stimulates the differentiation of immune system cells called monocytes into macrophages. Macrophages accumulate lipids to form foam cells which thicken the walls of the artery. Antioxidants such as those evaluated in the current study could help protect against this process by preventing LDL oxidation.

“Regular intake of foods rich in lycopene and other antioxidant vitamins may slow the progression of atherosclerotic processes and modify the early stages of atherosclerosis, with a consequent reduction in cardiovascular events, ” the authors conclude.

OXIDATIVE STRESS PROFILE (blood)

1. Malondialdehyde

2. Glutathione

3. CoEnzyme Q10

4. Vitamin C

5. b-Carotene (including cryptoxanthin and lycopene)

Supplements to consider taking to lower “bad” cholesterol and heart disease

Remember as a rule of thumb that most nutritional supplements work best together rather than as individuals, and you should use natural forms and not synthetic.

1. Anti-oxidants to help prevent the oxidation of cholesterol include:

a) vitamin e

b) vitamin c

c) co q10

d) bioflavanoids

e) alphalipoic acid

f) lycopene

g) selenium

h) beta carotene

2. Fish oil

There is overwhelming evidence for the reduced risk of cardiac disease and the use of omega 3 fishoil. Fishoil has enormous health benefits, even over and above cardiovascular disease reduction.

The heart and blood vessel benefits include:

a) decreased liporotein (a), triglycerides and blood pressure

b) elevation of hdl

c) reduction of inflammation in the blood vessel walls

d) endothelial function improvement (inner lining of blood vessel walls)

e) makes blood less likely to form clots

f) reverses and stabilizes plaques

g) contributes to the energy of the heart

h) counteracts dysrhythmias (irregular heart beats)

3. Magnesium

A lot of heart disease sufferers, especially diabetics and postmenopausal women, and acute disease are magnesium deficient. Magnesium helps so many heart conditions including arterial disease, stroke, ischaemic heart disease, heart failure, high blood pressure.

4. L-arginine

An aminoacid that improves nitric oxide, which relaxes arteries, promotes blood flow and keeps them flexible.

5. Some supplements to lower bad cholesterol:

a) RED YEAST RICE, for example Solal’s Cholestaway
A red powder powder produced by the fermentation of a strain of monascus purpureus
It is an antioxidant, may lower LDL cholesterol, increase HDL cholesterol and decrease triglyceride levels
It may inhibit HMG coA reductase as do statin drugs, and Coenzyme q10 supplementation is recommended as with statin drugs
Redyeast rice may also lower LDL cholesterol Contraindications include:

  • the use of grapefruit juice increases levels 15 fold when used in conjuction
  • not to be used in pregnancy or lactation

  • With high doses of nicotinic acid (>1g/d)

  • increased risk of muscular breakdown (rhabdomyolysis)

The usual dosage is 600-2400 mg/d taken as 1 to 4 divided doses.

b) Policosanol

A group of related lipid alcohols (long chain fatty alcohols)
Policosanol may inhibit synthesis of endogenous cholesterol, may inhibit oxidation of cholesterol and may elevate hdl
Usual dosages are 5-20mg /day

c) Beta-Sitosterol

300mg / day may compete with cholesterol absorption in the small intestine, thereby reducing absorption of cholesterol
Beta sitosterol is an ingredient in mixed phytosterol products
Beta sitosterol is part of some formulas designed to lower blood cholesterol, treat enlarged prostate (due to 5alpha reductase inhibition)
Or treat endogenous testosterone levels
General therapeutic doses are 60-130mg /day

d) Niacin / nicotinic acid

A special form of vitamin B3
Benefits include :
a) life extension properties due to surtuin gene activation
b) cardiovascular benefits include :
reversal of atherosclerosis, improvement of blood circulation, helps prevent abnormal blood clotting, may lower heart attack risk, may alleviate raynaud’s disease, lowers LDL, increases HDL, decreases VLDL, may inhibit crosslinking, may lower lipoprotein (a), lowers triglycerides.

side effects include: diarrhoea, nausea, muscle cramps, headaches, dry skin, erythema, flushing.

Niacin is an overlooked, wonderful supplement, that has lost favour to statin drugs. Niacin should be revisited and considered by more people wanting natural ways to manage their cholesterol and health.

6. Vitamin k2

Mk7 is a form of vitamin k2.
The most familiar vitamin k is vitamin k1 found in green leafy vegetables or supplements.
Vitamin k2 is less easy to find. It is found in fermented Japanese soy dish natto as well as in fermented and curderd cheese.
Both vitamin k1 and k2 are important for the health of the skeletal system as well as the heath of the blood vessel system, but vitamin k2 is the more beneficial. Vitamin k2 supplementation equates to better bone health and heart and blood vessel health.

7. ATP/ energy enhancers

A) Coenyzme q10 and solal’s superior form idebenone does so many good things and should be seriously considered for those seeking good health as they get older.

Coq10 does the following :

a) slows the aging process and helps prevent disease

b) helps heart disease sufferers

c) reduces hypertension

d) generates energy and strength

e) enhances the immune system and helps reduce cancer risk

f) counteracts depletions caused by statin drug therapy

g) improves neurological disorders

h) protects against gum disease

B) L-carnitine

L-carnitine helps transport fatty acids into the mitochondria to produce ATP (the molecule of energy). It also transports waste, aterial out of the mitochondria

C) D-ribose

“A new kid on the block” it rapidly restores depleted energy in sick hearts since it is a building block of ATP.

8. Others, and so many more!!

a) Pomegranate juice : lowers blood pressure, reduces oxidized cholesterol, decreases carotid artery wall thickness

b) Garlic contains powerful sulphur and selenium compounds used for the prevention and treatment of diseases for many years

c) B vitamins like B6, B12, folic acid help lower homocysteine and cardiovascular disease

References:
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3. Rasouli ML, Nasir K, Blumenthal RS, et al. Plasma homocysteine predicts progression of atherosclerosis. Atherosclerosis. 2005 Jul;181(1):159-65.
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17. Harvey PJ, Picton PE, Su WS, et al. Exercise as an alternative to oral estrogen for amelioration of endothelial dysfunction in postmenopausal women. Am Heart J. 2005 Feb;149(2):291-7.
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19. Lteif AA, Han K, Mather KJ. Obesity, insulin resistance, and the metabolic syndrome: determinants of endothelial dysfunction in whites and blacks. Circulation. 2005 Jul 5;112(1):32-8.
20. Newby DE, McLeod AL, Uren NG, et al. Impaired coronary tissue plasminogen activator release is associated with coronary atherosclerosis and cigarette smoking: direct link between endothelial dysfunction and atherothrombosis. Circulation. 2001 Apr 17;103(15):1936-41.
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22. Papamichael CM, Aznaouridis KA, Stamatelopoulos KS, et al. Endothelial dysfunction and type of cigarette smoked: the impact of ‘light’ versus regular cigarette smoking. Vasc Med. 2004 May;9(2):103-5.
23. Suvorava T, Lauer N, Kojda G. Physical inactivity causes endothelial dysfunction in healthy young mice. J Am Coll Cardiol. 2004 Sep 15;44(6):1320-7.
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Beauty From Within!

beauty-from-within

Beauty From Within!

Protecting your vital organs – your heart, brain, lungs, liver and kidneys – will ensure your longevity. The secret lies in the nutrients you put into your body.  The key to longevity is in the preventative, rather than the curative. Anti-aging specialist physician Dr Craige Golding believes that adding years onto your life isn’t the answer, but rather, ensuring that those years are healthy ones.

As you age, so your body’s demands for nutrients increases to help fight off disease, ageing and decay. Many of your body’s systems, such as the digestive, excretory and circulatory system become tired from years of use, functioning less efficiently.

Both Golding and registered dietician Celeste Naude agree that you need to make sure the foods you eat are wholesome, have as many vitamins and minerals in them as possible and are rich in both fibre and antioxidants.

Just look at the role-models for longevity – the Okinawans.  Research shows that this culture eats 30 to 40 percent less calories than that of the Western world, while their flavonoid consumption is up to eight times more than the Western world, and their daily exercise programmes are moderate to high. It is not unusual for the Okinawan people to live to 100 years and beyond.

“People who keep a healthy weight throughout most of their lifespan and have a healthy, balanced, primarily plant-based diet living longer, healthier lives,” adds Naude.

It is vital that you maintain your own energy balance, as this not only helps you sustain a healthy weight, but can reduce the risk of developing chronic lifestyle conditions associated with being overweight or obese, Naude shares. These includes heart disease, high blood pressure, high cholesterol levels, diabetes and obesity-related conditions.

One way to all-over body protection, is a diet rich in antioxidants (found in fruits, veggies and whole grains) as these help to prevent free radical destruction of cells and the oxidative damage that promotes aging. However, remarks Naude, these antioxidants work best when they are taken from food sources, rather than taken in supplement form.  Naude adds that while all nutrients have very specific functions, they work together in the body, and are often dependent on one another for optimum functioning. “By focusing on single nutrients, we are ignoring the complexity of the role of food in disease prevention and treatment.”

With this in mind, individual anti-aging nutrients need to be taken into context, and if you are going to supplement, make sure you do so wisely and always read the labels on your packaging. If you are not sure about what added nutrients you need, speak to a reputable health care expert.

Brain:

Your brain is a complex system that is the object of much research, and scientists believe that they have just scrapped the surface in understanding how the brain works and what it needs for optimal functioning. What is known is that besides being the centre of the body’s mechanical process, it is also our centre for reason, emotion, learning and memory.

Naude believes that omega-3 fatty acids are vital for optimum brain functioning, and requires more omega-3 fatty acids than any other system in the body. Two important fatty acids to look out for are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which play vital roles in development and function of the brain, including the transmission of nerve impulses and protection from oxidative stress. “Omega-3 levels in membranes of the brain are affected by the type and amount of fatty acids in the diet, and change with life stage, increasing with development and decreasing with aging. With sufficient quantities of EPA and DHA in the diet, the membranes of the brain can function well,” she explains.

The best natural forms of these fatty acids come from oily fish, in particular salmon, mackerel, herring, tuna, snoek, trout, sardines and pilchards.

Other vitamins and minerals to include in your diet include:

  • Folic acid (found in bananas, orange juice, fortified cereals, lemons, strawberries, leafy vegetables, dried beans and peas) as this plays a key role in the metabolism of the long-chain fatty acids in the brain
  • Vitamin B12 (found in eggs, meat, fish, poultry, milk and diary products) as this aids in maintaining healthy nervous tissue
  • Vitamin B1 (whole grain and grain-enriched products and pork) vital for healthy brain and nerve cells
  • Pantothenic acid (meat, poultry, fish, whole-grain cereals, legumes, milk, vegetables and fruit) helps in the transmission of nerve pulses.
  • Vitamin B6 (chicken, fish, pork, liver, kidneys, whole grain cereals, nuts and legumes) as this plays a role in the conversion of tryptophan into serotonin, a vital brain chemical.

Heart:

The small fist-sized organ found in your chest pumps to keep you alive. If this organ fails, or has too much strain, oxygen to your body decreases and your systems begin to shut down. This is why it is so vital to keep this organ healthy and strong.

The three top anti-aging nutrients for your heart, explains Naude, are vitamin B1 or Thiamin, Vitamin E and omega-3 fatty acids:

  • Vitamin B1 is needed for optimal heart function and is found in pork, seafood, wheat germ, whole and enriched grains, potatoes, watermelon and oranges. “This vitamin does occur in many foods in small amounts,” she adds.
  • Vitamin E has an antioxidant function, helping to prevent damage to cells that could potentially contribute to cardiovascular disease and cancers. Contained in vegetable oils, fortified cereals, green leafy vegetables, nuts, beans and whole grains, this vitamin provides a protective role.
  • Omega-3 fatty acids are again vital, helping to reduce the risk of arrhythmia, which can lead to sudden cardiac disease, decreases triglyceride levels and helps to reduce the growth of atherosclerotic plaque, which allows for optimum levels of blood to be pumped through the body.

Lungs:

The respiratory system is the combination of organs and tissues that aid in the process of taking in oxygen and releasing the waste product of carbon dioxide explains Golding. His research reveals that electromagnetic radiation can help improve your respiratory system. “Negative ions may reduce respiratory rate and may increase the secretory performance of the mucous membranes of the respiratory system and may improve the movement of the cilia,” he explains.

And, when your grandmother insisted that an apple a day would keep the doctor away, she wasn’t far wrong. Golding suggests that in one study, people who ate five or more apples a week, had fewer obstructions in their air passages compared to those who didn’t eat the fruit.

Herbs, such as goldenseal, horseradish and peppermint have all been shown to improve the general function of the respiratory system, while helping to clear the passages (particularly if you succumb to a cold).

Kidneys:

We don’t generally give much thought to our kidneys, unless there is something wrong with them, but they are more important than we give them credit for.  The kidneys are a pair of organs situated at the back of your abdomen, below the diaphragm. Their main responsibility is the disposal of waste material from the blood. But these little organs affect many of our other systems including the cardiovascular system, our metabolism as and hormonal balance.

Golding explains that kidneys help to regulate blood pressure, as erythropoietin, the hormone which controls the formation of red blood cells, is produced in the kidneys. Your kidneys, explains Golding, also monitor the quality of your blood so that your body isn’t poisoned by the end products of its own metabolism and the proper volume and composition of its body fluids is maintained.

“Approximately 25 percent of the blood pumped by the heart each minute is filtered by the kidneys and toxins are excreted from the body via this filtration mechanism.” Natural creatine is manufactured by your kidneys, from arginine, methionine and glycine as well as the active form of vitamin D, from its precursor calcidol.

Your kidneys are also the primary organ responsible for maintaining your body’s water balance.

Naude suggests that the important nutrients your kidneys need to maintain health and starve off illness include potassium and sodium:

  • Potassium (which is found in all animal and plant foods, but in particular, whole foods that are not processed) is important in maintaining water and electrolyte balance.
  • Sodium (found in table salt, soy sauce, meat, milk products and bread) regulates the water and electrolyte balance, while maintaining regular acid-base balance.

However, cautions Naude, this doesn’t give you free reign to liberally salt your food. You shouldn’t be consuming more than a teaspoon of salt a day, she adds.

Golding recommends that you look after your amino acids for optimum kidney health. Amino acids, both produced naturally in your body, as well as found in food sources, are you body’s building blocks. He suggests that arginine may improve the function of your kidneys, and help prevent age-related degeneration, while glutamine is essential for optimal health. If your body is lacking in these amino acids, you can supplement.

“Supplemental melatonin may help to prevent kidney damage caused by doxorubicin and mercury,” adds Golding. Mercury can potentially be present in some of the fish you eat, which in turn can potentially inhibit kidney function.

One of the most important anti-aging nutrients that you can take is water. “Water irrigates and cleanses the kidneys, and acts as a carrier vehicle for the excretion of toxins from the kidneys via urine,” Golding explains. Too little water in your diet, and your kidneys cannot function correctly. Ideally you should be drinking two to three litres of water a day, but this can also be taken in the form of herbal and green teas. Green tea itself is known to enhance the function of your kidneys, and you can give your self some extra protection by adding the herb lemon grass to your tea, as this too has health benefits.

“Interestingly, the supplement spirulina can help prevent damage to the kidneys caused by kidney stones, while watermelon has been claimed to ‘clean’ the kidneys,” Golding adds.

How do you know if you have a kidney malfunction – check your feet, suggests Golding as excessive foot odour is a sign of kidney problems.

Liver:

According to the British Liver Trust, your liver has more than 500 functions, quite impressive for such a small organ. Briefly, your liver processes digested food from the intestine, controls levels of fats, amino acids and glucose in the blood and combats infections in your body. Plus, it clears the blood of particles and infections, and helps to neutralise and destroy drugs and toxins. It manufactures bile, stores iron, vitamins and other essential chemicals and helps break down your food, turning it into energy. It also regulates hormones, including your sex hormones and makes enzymes and proteins which are responsible for most chemical reactions in your body, including those involved in blood clotting and the repair of damaged tissues.

All of this makes it vital to ensure that the organ is maintained and kept at an optimum health level. By protecting this organ, you are helping to prevent anti-ageing. Naude believes that the nutrients vitamin B3 or niacin will assist in keeping the blood flow healthy. However, she adds, diets with adequate protein intake will not likely be lacking in niacin, which is commonly found in meat, liver, poultry, fish, beans, nuts, whole and enriched grains, peas, mushrooms, asparagus and green leafy veggies.

Vitamin K also plays an important role in blood clotting mechanisms, and is found in leafy vegetables, cabbage, liver and to a lesser degree, in eggs, meats, cereals and other fruit and vegetables.

Another vital mineral is calcium as helps blood vessel contraction and dilation. Again, calcium is found in dairy products, broccoli, mustard and turnip greens, bok choy, parsley, watercress, canned fish containing bones, calcium fortified juice, soy milk , tofu and cereals.

Another important nutrient for the liver is resveratrol, a polyphenol that is found in blueberries, grapes and some nuts. Research shows that grapes grown in wet areas tend to have more resveratrol than others. This antioxidant is quickly absorbed, reaching your bloodstream in less than 30 minutes, and is metabolized rapidly by your liver. Studies reveal that resveratrol can protect the body from going into an inflamed state, one of the markers of aging. Aside from helping protecting the liver, it helps prevent plague buildup in the arteries, boosts nitric oxide levels, improves eye and bone health, and protect your joints.

All in all, the experts agree, that it is what you take into your body now, that will help protect you against rapid or early aging later on. “It’s not that we want to delay death, or increase our longevity substantially, but rather ensuring that the years we do have are of high quality. Who wants to be 90 and infirm?” remarks Golding.

Longevity rules:

Follow the example of the Okinawan people:

  • Seven servings of fruit and veggies per day
  • Seven servings of grains per day
  • Two servings of soy-laden foods rich in flavonoids
  • Two to three servings of foods rich in omega-3 fatty acids per week
  • Also get 30 percent of your total calories per day from fat
  • Have less than six grams of sodium intake from all sources per day.
  • If you are not sure you are getting your daily vitamin and mineral intake needed, take supplementation.
  • Participate in moderate exercise daily.
  • Have a strong social and family network
  • Focus and calm your life, by utilising relaxation and meditation techniques.
  • Everything in moderation, and balance your life.

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