Monthly Archives: September 2020

Can an apple a day help keep cancer away?

Can an apple a day help keep cancer away?

National Foundation for Cancer Research News|September 15, 2020

It’s a saying as old as time – an apple a day keeps the doctor away.

Over the years, many have questioned the validity of this well-known statement. Can one piece of fruit be the key to keeping healthy and well?

While the debate may never truly be settled, researchers from the University of Perugia (Italy) found that people who frequently eat fruit often have fewer tumors. Apples are one of the fruits that boast a large amount of dietary fiber and polyphenol compounds that partner with gut microbes to create an environment that may reduce one’s risk of cancer. This environment is predicted to reduce the risk of several specific cancers, including lung, bowel, mouth, digestive tract, and breast tumors, when compared to people who do not consume apples regularly.

The vitamin C in apples also acts as an antioxidant to support immune function and fight cancer cell growth. In addition to preventing tumors, apples may also support cancer recovery. The amount of potassium found in apples can positively affect one’s fluid balance and prevent fluid retention, which is a common side effect of chemotherapy.

Though eating an apple a day may not be the key to never falling ill, the popular fruit may greatly contribute to one’s overall well-being. Luckily, including an apple into one’s diet is easier than ever. In recent years, apples have become an extremely popular tool in the kitchen. They can be used for breakfast, lunch, dinner, dessert, and of course, a snack between meals.

Foods that make you hungrier

Foods that make you hungrier

Charlie Williams|September 14, 2020

No matter what we eat, hunger is seldom more than a few hours away. Though sometimes it can feel like hunger is seldom more than a few minutes away, even after we just ate.

Foods with ’empty’ calories can make you feel hungry again soon after eating them.

Why? When we give our bodies high-quality nutrients, we receive enduring energy that wards off hunger. Low-quality nutrients burn more quickly, requiring us to eat again sooner. These four foods can contain more calories, but may make you hungrier.

Yogurt

Yogurt is consistently touted as a healthy snack, and by itself, it typically is. However, most commercial yogurts are a dessert-like hybrid of yogurt and sugar. For example, Dannon Fruit on the Bottom Blueberry yogurt has 20 g of sugar per 5.3-oz container—that’s about 28% of your daily recommended value (DRV) of sugar and more than half of the sugar you’d find in a 12-oz can of Coke. On top of that, it has relatively little protein, just 5 g per serving.

The combination of high sugar and low protein means a cup of sweetened yogurt will leave you feeling hungry again in no time. Added sugars are notorious for being “empty calories”—foods that do a poor job satiating hunger because they are high in calories but offer few or no other nutrients. Protein, on the other hand, is incredibly effective at satisfying hunger. Unfortunately, you won’t find much in most sweetened yogurts.

Luckily, you can still enjoy some yogurts and rid yourself of hunger—just mind the nutrition label. A 5.3-oz cup of Chobani non-fat plain Greek yogurt has 14 g of protein (28% of your daily recommended intake) and just 4 g of sugar. For those who can’t do without the sweetness, experts recommend adding some fresh fruit to the mix.

Cereal

The bad news: Like yogurt, most cereals are a dessert-like hybrid of cereal and sugar. For example, a single serving of Kellogg’s Frosted Flakes has 12 g of sugar (24% DRV), just 1 g of protein, and <1 g of fiber. Studies have shown that while fiber doesn’t pack much of a nutritional punch, it reduces feelings of hunger by increasing digestion time and slowing the emptying of the stomach.

The good news: Like yogurt, it’s all about reading the nutrition labels and making a smart choice. Some cereals are effective at reducing hunger, like Kashi Go Original. It packs 12 g of protein (17% DRV), 13 g of fiber (46% DRV), and 8 g of sugar (14% DRV). Pouring whole milk over cereal adds another 8 g of protein to the mix.

Refined grains

Refined grains like white bread and white rice might feel filling at first, but they lack the sustainable hunger-fighting powers of whole grains, such as whole wheat bread and brown rice. In one study, researchers found that people who consumed three or more slices of white bread daily were 40% more likely to be obese than those who ate just one portion of white bread weekly.

“The issue is that white bread is made with highly refined flour, which is rapidly absorbed as sugar,” the study’s lead author told The Independent. “Essentially it is equivalent to a high consumption of sugar. The problem is similar to what we see with soft drinks, their sugars are rapidly transformed into fat.”

Another issue? The refining process removes the bran and germ. This gives the grains a finer texture and improves shelf life, but also removes dietary fiber, iron, and many B vitamins present that are much more effective at satiating hunger. Even enriched grains—those that have been refined but subsequently “enriched” with some of the vitamins they lost in the process—are not re-enriched with fiber.

Foods high in sodium/salt

Monosodium glutamate (MSG) is a flavor enhancer, notably used in many Americanized Chinese foods, but also common in chips, condiments, frozen meals, and soups. If you’ve ever consumed any of these foods and felt hungrier afterward, MSG could be the cause. In one study of 24 men, 1% added MSG in soups significantly increased flavor but resulted in a much smaller decrease in hunger. Added MSG also resulted in reduced feelings of fullness immediately after consuming the soup, even though it was high in protein.

Other studies, however, suggest that MSG has little effect on appetite. Another potential explanation is that all of the aforementioned foods are high in salt, which studies have shown induces body water conservation, decreases fluid intake, and can also increase feelings of hunger as a result, leading to weight gain.

“It makes sense that on a high-salt diet, the body wants to prevent water loss,” Jens Titze, MD, told Health.com. “So the kidneys have to find a way to increase water content—and if you have more water content in your body, you’re going to be less thirsty.” All of that extra water retention consumes significant energy, which could be the cause behind increases in appetite.

Bottom line

Whether a snack or meal is satiating comes down to its nutrient content. Protein and fiber go a long way toward long-term satiety, while empty calories like sugar and refined grains can make you feel hungrier—or hold you over for short periods, at best.

Oestrogen in HRT.

I often get women questioning me about the difference between the normal HRT as prescribed by their GP or specialist, and the bio-identical hormones I use. They are often told that they are the same, and that the HRT their doctors use are also the same as what they make naturally. One of the great benefits of the oestrogen I prescribe for most of you, is that I use Biest. It contains between 70-80% of oestriol, a gentle and balancing hormone, which is considered to have anti-breast cancer properties. Oestriol is not included in any of the synthetic hormones doctors prescribe. Here is more information about Biest, so that when your doctor has a go at you for being on BHRT, you have some information to defend yourself. Most doctors are oblivious to the benefits of oestriol, if they even know of its existence. So when you look at the word “Biest”on your script, this is what you are getting.

Biest (Medication) Guide for Menopause: Side Effects, Dosing & More

Biest may be the preferred way to treat low estrogen in the setting of menopause.

Learn more about why this combination medication is preferred to other formulations, how it works in your body, how it may be protective against breast cancer, how to dose it and more:

Bio-Identical Hormone Replacement Therapy & Biest

Bio-identical hormone replacement therapy is the use of hormones which look exactly like the hormones your body produces naturally.

These hormones are then given to patients to relieve problems associated with hormone imbalance (such as low estrogen).

Biest is a perfect example of a bio-identical hormone and it is often (or should be) used to treat cases of low estrogen and menopause.

But what exactly is biest?

Biest is a combination of estrogens formulated into one compound.

Thus the name “bi” (meaning two) and “est” (referring to estrogen).

list of bioidentical vs synthetic estrogens

The two estrogens included in this are estradiol and estriol.

Estradiol is considered the most powerful and most potent estrogen in the female body while estriol is considered a much weaker estrogen (1).

Biest is most often used as part of HRT (hormone replacement therapy) for women who suffer from menopause and low estrogen.

Because of its unique properties, it may be preferred when compared to synthetic estrogens such as those found in birth control pills (2).

Using Biest for Menopause & Low Estrogen

Does using biest have any benefits over more traditional medications such as estradiol?

The answer is probably and here’s why.

Biest includes a combination of the most powerful estrogen that your body produces naturally (estradiol) and a weaker, more protective estrogen (estriol).

In order to understand the benefit, you need to know just a few basics about HRT.

The first has to do with the concern over using estrogens and estrogen therapy to treat low estrogen.

In the early 2000’s there was a study (the Women’s Health Initiative) which showed that using estrogen, specifically in the setting of menopause, may lead to an increased risk of heart disease (heart attacks), breast cancer, stroke and venous thromboembolism (3) (blood clots).

Up until this point up to 30-40% of women who were post-menopausal were using HRT (4) which was being actively prescribed by Doctors.

The women undergoing treatment for HRT during this time were experiencing significant relief from their symptoms but were placed at an increased risk of the events listed above.

This caused a massive shift in thinking among physicians and MANY women were pulled off of HRT in a hurry.

percentage of women using HRT prior to 2002 and after

This study has had a lasting impact on many physicians who are unwilling to prescribe HRT due to this perceived risk (5).

The problem with the study is that it tested what are known as synthetic estrogens, such as Prempro, Premarin and progestin (pharmaceutical variants of actual hormones that females produce naturally).

Even though these hormones are NOT the same as the hormones that your body produces naturally (these are referred to as bio-identical hormones), both bio-identical and synthetic hormones have been lumped into the same category in terms of these risks.

The problem with this is that many studies show that the negative side effects seen in this study may have been primarily due to the fact that these hormones were synthetic and not bio-identical (6).

This is a long introduction to biest, but this is where biest takes center stage.

Studies have shown that there is indeed a difference between how stimulatory certain estrogens are on tissues such as breast tissue and endometrial tissue.

What this means is that there are weak estrogens and strong estrogens, and some estrogens may be balancing the effects of stronger estrogens (7).

Estriol is an example of one of these weaker estrogens and one that has the potential to combat the increased potency of estradiol (8) (especially when used alone).

In fact, newer studies have shown that the use of bio-identical hormones does not show an increased risk of these negative side effects (cancer, stroke, etc.).

Wouldn’t it be nice if you could use the exact same hormones that your body produces naturally to completely eliminate the symptoms of menopause, without experiencing the increased risk of heart disease, breast cancer and so on?

Well, that’s the logic behind the use of biest and other bio-identical hormones.

It’s important to realize that no hormone is perfect, however, so before you jump in and use biest you need to be evaluated by a physician to assess your own personal risk.

Dosing Based on Symptoms & Blood Tests

Another important factor, as it relates to risk factors and side effects, is the dose of your medication.

The best approach to take, when using hormones, is to use the absolute minimum amount of hormone necessary to completely resolve all of your symptoms and without causing the symptoms of excess hormone.

This can be done by carefully monitoring your symptoms and by watching your serum levels of estradiol and progesterone (you can also assess your hormones via 24-hour urinary testing as well).

Biest is usually formulated with 80% estriol and 20% estradiol.

This ratio can be adjusted based on the needs of the individual.

For instance:

Your Doctor may prescribe 70% estriol and 30% estradiol or even 90% estriol and 10% estradiol.

The idea is to use no more estradiol than necessary to help reduce the symptoms of menopause and to balance that with a sufficient amount of estriol.

The estradiol component of biest can be manipulated (either up or down) if you are struggling with persistent symptoms.

Remember:

Estradiol is the most potent estrogen in the body and the symptoms of menopause tend to be primarily caused by the reduction in estrogen (9) (estradiol) produced naturally by your ovaries.

In order to achieve symptomatic relief, you NEED some estradiol, but you don’t want to use too much.

Women who are post-menopausal, and experiencing side effects such as hot flashes, weight gain, and depression, will often notice a near immediate reduction in their symptoms when starting biest (10).

Dosing can be started at a very low dose and increased until the side effects stop.

While you are adjusting your dose make sure that you monitor for symptoms of excess including breast tenderness and menstrual bleeding (more on side effects below).

Your Doctor can, and should, work with you as you start biest to help titrate and tweak your percentage to find an optimal level for you.

This may take some trial and error, so be patient!

As a provider, and after treating hundreds of patients, I can tell you that no two women are exactly alike.

The amount of hormone that they require will be different and unique to their body.

But taking this approach has allowed me to help 98+% of women suffering from menopausal symptoms.

Application (How to use Biest effectively)

So, how do you use biest if you plan to take it?

Biest is usually formulated in either a cream, Troche or a gel by a compounding pharmacy.

This may be different from other hormones you are used to taking because most medications are taken orally (meaning by mouth).

Taking hormones transdermally (through the skin) or via injection (with a shot) is usually better when compared to orally due to the avoidance of the first pass metabolism by the liver (11).

When you take a medication by mouth, the medication must go through the intestinal tract where it is absorbed and then processed directly by the liver via the portal system.

The liver will then break down a large percentage of the hormone into smaller pieces to help your body get rid of it.

This may lead to concentration of the hormone in the liver which can stimulate hepatic protein synthesis and may increase inflammatory markers and markers of coagulation and so on (12).

The use of oral estrogen also dramatically increases the creation of sex hormone binding globulin which can bind to and inactive testosterone (which is in low supply during menopause!).

Once the hormone is broken down it is then sent to the heart where a portion of the original hormone absorbed is directed to your cells and tissues.

This process should be compared to the natural process that your body goes through when it releases hormone through endocrine glands (hormone glands).

Your body releases hormone directly into the bloodstream where your hormones go straight to target tissues FIRST as opposed to being broken down by the liver first.

In almost all cases, it’s best to mimic the natural flow of the body when using hormone replacement therapy.

For this reason, the transdermal route may be preferred over oral medication.

In addition, when using biest, you’ll also want to make sure that you put it on the appropriate place on your body.

The forearms are perfect “real estate” for hormone application because the skin is thin (13), there isn’t very much fat there and your superficial veins will carry the hormone directly to your heart for pumping throughout the body.

Other areas that biest can be used include the inner thighs, vaginal area, peri-anal area, and neck.

If you are using other hormones, such as testosterone or progesterone, make sure that you do not apply more than one hormone to the same spot on your body at a time.

Some hormones, such as progesterone, will need to be alternated each time you use them.

Another quick tip:

Estrogen has an enhancing effect on the skin and can help reduce wrinkles/age spots (14).

Some patients will apply their biest to their forearms and then do a quick swipe of hormone on the back of their hands, neck and even face.

You don’t want to apply the hormone to these places directly, but a small residual amount may work wonders!

Side Effects to Watch out for

Side effects from biest tend to come from either underdosing or from overdosing.

It would be unusual to respond directly to the active hormones because your body has been producing them naturally for many years (remember they are bio-identical).

With this in mind, you can imagine a scenario in which you might be reacting to the absolute dose vs the hormone itself.

For instance:

Using an insufficient dose will lead to the persistence of symptoms such as hot flashes, weight gain, and depression.

This does NOT mean that the medication is causing these symptoms, instead, it may mean you need to increase your dose.

Symptoms that you are not using enough biest may include:

  • Persistent hot flashes
  • Persistent weight gain
  • Persistent mood issues or depression
  • Persistent vaginal dryness and decreased libido
  • Persistent night sweats or insomnia

On the other hand, it’s also entirely possible that you are using TOO MUCH hormone and may be experiencing side effects associated with excessive dosing.

This would be an indication to cut down on your dose because excessive dosing may lead to overstimulation of estrogen receptors and may increase your risk (if continued long-term) of breast cancer and so on.

You can find a list of excessive dosing below:

  • Breast tenderness
  • Menstrual bleeding
  • Abdominal cramping
  • Water retention or bloating
  • Nipple tenderness
  • Breast fullness or enlargement (with or without tenderness)
  • Pelvic cramps (with or without bleeding)
  • Continued hot flashes at very high doses (hot flashes may subside and then persist if dosing is extremely high)

When using biest ensure that you do NOT experience the side effects listed above.

If you do, then reducing your dose (or stopping for 2-3 days) should be sufficient to bring you back to normal.

If there is any confusion about your dose make sure to discuss it with your physician or re-order blood tests.

How to get Biest from your Doctor

In order to get biest, you will need a prescription from a physician (MD or DO).

Most conventional doctors, such as family practice doctors or endocrinologists, may not be familiar with using biest or other bio-identical hormones.

The reason for this has to do with the fact that hormone replacement is not taught in medical school.

So, in order for a physician to be knowledgeable on the subject, they usually have to take extra classes or courses to help bring them up to speed.

The logic and theory behind bio-identical hormone use are also vastly different from the conventional hormone replacement therapy model that standard physicians use.

Conventional doctors don’t have a problem giving out massive doses of insulin, birth control or steroids, but they seem to have a problem when it comes to bio-identical hormones.

Much of this simply has to do with the fact that they are not educated on the topic.

It’s my experience that most physicians when they see how effective these hormones can be, and when they are confronted with the studies that show they are effective (15), they tend to be willing to give them a try.

But having this discussion is generally not worth your time or effort when you can find a physician who specializes in hormone replacement therapy relatively easily.

If you are interested make sure you look for a doctor that specializes in Integrative medicine, Anti-aging medicine or functional medicine.

Most women find that their symptoms are taken more seriously and they are “listened to” by integrative Doctors compared to conventional physicians (this is actually seen in studies (16)).

Final Thoughts

Biest is a combination medication used to treat low estrogen which can also be very effective in menopause.

This formulation of estrogens contains both estradiol and estriol and may be superior when compared to just estradiol alone.

Estriol may help to reduce the powerful impact that estradiol has on breast and endometrial tissues by acting as a minor anti-estrogen.

If you are considering using HRT for menopause then biest may be the preferred option because it is bio-identical and contains a more complete hormone profile when compared to generic pharmaceutical medications.

As always, ensure that you titrate your dose based on your body and on your symptoms.

Doing this should reduce your risk of negative side effects.

A Current Affair

Last night a Current Affair had an interview with Dr Kerryn Phelps about HRT and breast cancer. I assume she was talking about the standard HRT most doctors use, and does not practice HRT the way that i do. I strenuously disagree with most of what she said, and I have had many blogs over the years on this topic. As well, I have reprinted evidence from the worlds best hormonal experts and organizations, about HRT and breast cancer. I will republish those blogs as soon as I have time. Dr Phelps may be a good GP, but I do not know how much she knows about HRT. Professor John Studd, the one person who knows more about hormones than any one else on earth ( see his CV published here) says they are very safe.

clinical gynaecologist

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Biography

Dr. John StuddProfessor John Studd, DSc,MD,FRCOG was Consultant Gynaecologist at the Chelsea & Westminster Hospital, London and also Professor of Gynaecology at Imperial College. He qualified in 1962 and has worked and trained in Birmingham. Zimbabwe and London. He was Consultant Gynaecologist in Salisbury, Rhodesia and Consultant and Senior Lecturer at the University of Nottingham and moved to London in 1974 as Consultant Obstetrician and Gynaecologist at King’s College Hospital. Six years ago he was invited to join the staff at the new Chelsea & Westminster Hospital, London.

His early research was on chronic renal disease and high blood pressure in pregnancy (MD thesis) but later started the first menopause clinic in the county in Birmingham in 1969. This hormone treatment for the menopause was so controversial at that time that the clinic was closed down for three months following protests from the BMA. However, the optimism placed in HRT has been confirmed and John Studd has continued to work on specific treatments for menopausal symptoms. He pioneered the sequential oestrogen/progestogen treatment and also the continuous combined oestrogen/progestogen non-bleeding treatment. He has championed the use of hormone implants for women with osteoporosis or with severe depressive or sexual problems after the menopause and as an almost routine route of HRT after hysterectomy.

He first described the use of oestrogen patches and oestrogen implants for the treatment of severe PMS and runs a PMS/Menopause clinic at the Chelsea & Westminster Hospital, the Lister Hospital and the Wellington Hospital.

He is also shows the efficacy of moderately high dose transdermal oestrogens for the treatment of hormone responsive depression in women, particularly post-natal depression, pre-menstrual depression, menopausal depression and post-hysterectomy depression. He has a D.Sc. for 25 years of published work on oestrogen therapy in women. He has written more than 500 scientific articles and written or edited more than 25 post-graduate books on gynaecology and realises the he needs to write one for the public. This is much more challenging.

He is Founder and Vice-President of the National Osteoporosis Society and has been a Council Member of the Royal College of Obstetricians and Gynaecologists for 12 years and a Past-President of the Section of Obstetrics and Gynaecology at the Royal Society of Medicine. In 2005-2007 Professor Studd was Chairman of the British Menopause Society.

From Prof. Studds Website:

  • HRT is safe
    In spite of the press reports stressing bad news, even the investigators have withdrawn virtually all of the major side effects from the WHI study. It seems quite clear that the major side effects occurred in women who started the wrong dose of HRT over the age of 60. In women who started below the age of 60 there were fewer heart attacks, fewer deaths, fewer osteoporotic fractures and even less breast cancer. The one residual side effect is that there probably is a very slight i.e. 1% extra life time risk of developing breast cancer but this is no more than the breast cancer risk of being overweight, drinking wine, having no children or even taking statins.

Here we go again- HRT and Breast Cancer risk.

There has been media coverage of a study by Professor Emily Banks that says HRT increases menopausal women’s risk of breast cancer (BC). This comes up frequently, as women are naturally concerned about any connection between the two. This means I will spend the next month reassuring my patients that the way I do it is very safe, and I will explain the reason I can say that below.

The study published in today’s media had a number of problems with it – they used mainly synthetic progestogen, and not natural progesterone. I have known (from many published studies, so it is no secret) that the synthetic progesterones increase women’s rick of BC. Natural progesterone does not. So why would any doctor give it to menopausal women? Beats me. Ask them for an explanation.

Secondly, most of the hormones used were in pill form. We have known for many years the HRT must be given transdermally (creams, patches or troches), and not as a pill. So why do doctors use oral forms of HRT (Like Livial, Xyvion, estalis, Kliovance, Kliogest, Femoston, Progynova, Premarin) Beats me. Ask them for an explanation.

Third factor – using one size fit all means many women get the wrong dose of hormone – tailoring the dose has to be better, so women get the lowest dose that works for them.

Personal experience – I have been using these BHRT for the last 25 years, in over 4500 women, and doing a statistical study of these women, I get about 4% BC incidence. BC occurs in about 13% of Australian women, so I know that there is no increase in BC in the women I treat – in fact the opposite. Unfortunately some of my patients do end up with BC – but it is below the national incidence.

Now lets look at the opposite – lives saved. Most women die from heart disease (estimate about 50%), not BC. HRT reduces women’s risk of heart disease significantly, so it actually saves lives. Then there is the quality of life issues, relationships saved and general well being on HRT.

Here are the relevant articles which I have published before: note they come from impeccable sources: You can find anything on the internet, so information should only come from respected medical journals, internationally respected researchers, and grade 1 universities.

Climacteric. 2012 Apr;15 Suppl 1:3-10.

What’s new in hormone replacement therapy: focus on transdermal estradiol and micronized progesterone.

Simon JA.

Source

Department of Obstetrics and Gynecology, George Washington University, Washington, DC 20036, USA.

Abstract

The original conclusions of the Women’s Health Initiative study have been questioned as a result of the availability of age-stratified data. Initial concerns regarding the risk of coronary heart disease (CHD) in association with the use of hormone replacement therapy (HRT) have been replaced with concerns regarding thromboembolic disease, encompassing venous thromboembolism (VTE), particularly in younger postmenopausal women, and stroke, particularly in older women. The original publication of the study results led to a dramatic decrease in the use of oral HRT; however, the use of transdermal HRT has increased over recent years.

 Guidelines from the North American Menopause Society, the Endocrine Society, the International Menopause Society, and specific guidelines from the Menopause and Andropause Society for the management of menopausal women with a personal or family history of VTE all contain positive statements regarding both transdermal estradiol and micronized progesterone.

Unlike oral estrogens, transdermal estradiol has been shown not to increase the risk of VTE, or stroke (doses ≤ 50 μg), and to confer a significantly lower risk for gallbladder disease. Unlike some progestogens, progesterone is also not associated with an increased risk of VTE, or with an increased risk of breast cancer. Based on these data, which are now included in the guidelines, the use of transdermal estradiol and micronized progesterone could reduce or possibly even negate the excess risk of VTE, stroke, cholecystitis, and possibly even breast cancer associated with oral HRT use

They reviewed all the guidelines form the major medical bodies that deal with hormones, and concluded that using transdermal oestrogen and micronised progesterone is the safest form of HRT.  Micronised is the form of natural progesterone used in Bioidentical HRT. This is not to be confused with progestogens, which is used mainly in the synthetic forms of HRT Progestogens largely are known as Provera, {Medroxyprgesterone acetate- MPA: or Norethisterone (Primolut-N).

This is the most recent medical publication re safety of HRT:Menopause. 2016 Jul 25. [Epub ahead of print]

Reduced risk of breast cancer mortality in women using postmenopausal hormone therapy: a Finnish nationwide comparative study.

Mikkola TS1, Savolainen-Peltonen H, Tuomikoski P, Hoti F, Vattulainen P, Gissler M, Ylikorkala O.

Author information

  • 11Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland 2Folkhälsan Research Center, Biomedicum, Helsinki, Finland 3EPID Research Oy, Espoo, Finland 4Information Services Department, National Institute for Health and Welfare, Helsinki, Finland.

Abstract

OBJECTIVE:

Data are controversial on the impact of postmenopausal hormone therapy (HT) on breast cancer mortality. We analyzed nationwide Finnish data on breast cancer mortality risk in women using HT consisting of estradiol-only therapy (ET) or estrogen-progestogen therapy (EPT).

METHODS:

In total, 489,105 women using HT in 1994 to 2009, traced from the nationwide reimbursement register, were followed from the HT initiation (3.3 million cumulative exposure years) to breast cancer death (n = 1,578 women). The observed deaths were compared with those in the age-standardized background population.

RESULTS:

The breast cancer mortality risk was reduced in all HT users with exposure for at most 5 years (standardized mortality ratio 0.56; CI 0.52-0.60), more than 5 to 10 years (0.46; 0.41-0.51), or more than 10 years (0.62; 0.56-0.68). A significantly larger risk reduction was detected in the 50 to 59 years age group (0.33; 0.29-0.37) compared with 60 to 69 (0.64; 0.59-0.70) or 70 to 79 (0.78; 0.69-0.87) years age groups. The death risk reductions in ET users tended to be larger in all age groups compared with EPT users, with a significant difference only in the 70 to 79 years age group (0.66; 0.57-0.76 vs 0.88; 0.77-1.00). The age at HT initiation, regardless whether ET or EPT, showed no association with breast cancer mortality.

CONCLUSIONS:

In the Finnish unselected population, breast cancer is fatal in 1 of 10 patients. Our data imply that this risk is prevalent in 1 of 20 patients with history of HT use. This is an important message for women considering or already using HT.Menopause. 2015 Sep;22(9):976-83. doi: 10.1097/GME.0000000000000450.

Estradiol-based postmenopausal hormone therapy and risk of cardiovascular and all-cause mortality.

Mikkola TS1, Tuomikoski P, Lyytinen H, Korhonen P, Hoti F, Vattulainen P, Gissler M, Ylikorkala O.

Author information

Abstract

OBJECTIVE:

Data on the health benefits and risks of postmenopausal hormone therapy (HT) are derived mainly from the use of conjugated equine estrogens. Estradiol-based regimens may have a different risk-benefit profile. We evaluated the risk of death caused by coronary heart disease (CHD), stroke, or any disease among users of estradiol-based HT regimens in a nationwide study in Finland.

METHODS:

A total of 489,105 women who used HT from 1994 to 2009 (3.3 million HT exposure years), as indicated in the nationwide reimbursement register and the national Cause of Death Register, were followed. A total of 28,734 HT users died during follow-up; among the deaths, 3,843 were caused by CHD and 2,464 were caused by stroke. Mortality risk in HT users with varying duration of exposure (≤1 y, >1 to 3 y, >3 to 5 y, >5 to 10 y, or >10 y) was compared with that in an age-matched background population.

RESULTS:

Risk of CHD death was significantly reduced by 18% to 54% in HT users and was positively related to HT exposure time. Risk of stroke death was also reduced by 18% to 39%, but this reduction was not clearly related to HT exposure time. Risk of all-cause mortality was reduced in HT users by 12% to 38%, almost in linear relationship with duration of exposure. All these risk reductions were comparable in women initiating HT before age 60 years and women initiating HT at age 60 years or older.

CONCLUSIONS:

In absolute terms, the risk reductions mean 19 fewer CHD deaths and 7 fewer stroke deaths per 1,000 women using any HT for at least 10 years.

Am J Public Health. 2013 Sep;103(9):1583-8. doi: 10.2105/AJPH.2013.301295. Epub 2013 Jul 18.

The mortality toll of estrogen avoidance: an analysis of excess deaths among hysterectomized women aged 50 to 59 years.

Sarrel PM1, Njike VY, Vinante V, Katz DL.

Author information

1 Departments of Obstetrics and Gynecology and Psychiatry, Yale University School of Medicine, New Haven, CT, USA. philip.sarrel@yale.edu

Abstract

OBJECTIVES:

We examined the effect of estrogen avoidance on mortality rates among hysterectomized women aged 50 to 59 years.

METHODS:

We derived a formula to relate the excess mortality among hysterectomized women aged 50 to 59 years assigned to placebo in the Women’s Health Initiative randomized controlled trial to the entire population of comparable women in the United States, incorporating the decline in estrogen use observed between 2002 and 2011.

RESULTS:

Over a 10-year span, starting in 2002, a minimum of 18 601 and as many as 91 610 postmenopausal women died prematurely because of the avoidance of estrogen therapy (ET).

CONCLUSIONS:

ET in younger postmenopausal women is associated with a decisive reduction in all-cause mortality, but estrogen use in this population is low and continuing to fall. Our data indicate an associated annual mortality toll in the thousands of women aged 50 to 59 years. Informed discussion between these women and their health care providers about the effects of ET is a matter of considerable urgency

Phytonutrients can boost your health. Here are 4 and where to find them (including in your next cup of coffee)

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Phytonutrients can boost your health. Here are 4 and where to find them (including in your next cup of coffee)

Coffee is regularly in the news for its potential health benefits and drawbacks.

A review of the research found drinking a few cups of coffee a day was associated with a lower risk of dying from any cause. Coffee drinkers had a lower risk of developing heart disease, type 2 diabetes, liver disease, depression, Alzheimer’s disease, Parkinson’s disease, and prostate, endometrial, liver and skin cancers.

However, the review also found evidence of negative effects related to pregnancy and fracture risk in older women, even after results were adjusted for possible confounding factors, like smoking.

Some of coffee’s positive effects have been attributed to food components called “phytonutrients”. But if you’re not a coffee drinker, don’t worry — you can find phytonutrients in other foods too.

What are phytonutrients?

Phytonutrients, or phytochemicals, are chemical compounds plants produce that help them grow well. They can deter predators or help fight off pathogens.

Research is shedding light on their potential benefits for human health, too. When we digest and absorb foods and drinks that are rich in phytonutrients, these compounds become active in our bodies’ biochemical pathways that affect our health and infleuence whether we develop disease.

Scientists have identified thousands of phytonutrients in plants including nuts, beans, seeds, vegetables, fruit and grains.

Research to identify those with potential for use in disease prevention and treatment is accelerating.


Read more: Health Check: four reasons to have another cup of coffee


Four phytonutrients

Two of the phytonutrients found in coffee beans are caffeic acid and chlorogenic acid. You’ll also find them in a range of fruit, vegetables, herbs and spices.

Caffeic acid is found in dates, prunes, olives, potatoes, sunflower seed meal, cinnamon, cumin, nutmeg, ginger, star anise, spearmint, caraway, thyme, oregano, sage and rosemary.

Chlorogenic acid is found in prunes, blueberries, apples, pears, peaches, globe artichokes, potatoes, sunflower seeds, spearmint, sage and oregano.

Most of the research on caffeic acid and chlorogenic acid has been in laboratory studies, so the results cannot be applied directly to people. But laboratory studies suggest these compounds act on signalling pathways that contribute to the development of chronic diseases, including cancer.

They may prevent cancer development by neutralising free radicals that can damage cell walls, and by converting potential cancer-causing substances into less toxic compounds.

Further, in studies in mice, caffeic acid and chlorogenic acid suppressed the rise in blood sugar levels after eating. These results suggest a mechanism for lowering the risk of developing type 2 diabetes, though we’ll need research beyond laboratory studies before we can move towards any conclusions.

Two women in a cafe talking and having coffee. Image focuses on their cups and hands.
Coffee is one source of phytonutrients — but it’s not the only source. Shutterstock

Among other phytonutrients with similar anti-inflammatory and protective properties are quercetin and glucosinolate.

Quercetin compounds give flowers, vegetables and fruit some of their colour. Quercetin helps plants adapt to local growing conditions and regulates the hormones that influence their growth and development.

Food sources include asparagus, black olives, cocoa, cranberries, buckwheat, prunes, broad beans, plums, apples, red and brown onions, shallots, blackberries, raspberries, strawberries, broccoli, red lettuce, red wine, green beans, zucchini, oregano, marjoram, cloves and capers.

While most studies of quercetin have similarly been in cells or animals, and not humans, they show quercetin has anti-inflammatory, antioxidant and anti-cancer effects. Quercetin alters the way cancer cells develop, grow and spread, and helps kill the cancer cells. So more research on quercetin as a potential therapeutic agent for cancer is warranted.

Quercetin supplements have been tested in humans for their effects on blood pressure. In a review of seven randomised controlled trials, both systolic and diastolic blood pressure were significantly reduced among patients taking quercetin.


Read more: Seven things to eat or avoid to lower your blood pressure


Glucosinolates give certain plants their pungent flavour. They’re found in brocolli, cabbage, Brussels sprouts, cauliflower, daikon radish, kale, wasabi, bok choi, rocket, horseradish, radish, turnip, watercress and mustard greens.

Food processing influences glucosinolate content, with steaming preserving more compared to boiling or blanching.

The bioactivity of glucosinolate is likely to have evolved as part of the plants’ defence systems against disease and insect pests. Laboratory studies in cells, mice and rats have shown glucosinolates exert antimicrobial activity, as well as anti-cancer activity by deactivating potential carcinogens.

We need more research to evaluate whether glucosinolates could be used to increase the effectiveness of current cancer therapies.

Radishes pulled out from the ground sitting in the dirt.
Radishes are among the plant foods that contain glucosinolates. Shutterstock

Putting it all together

While research progresses to identify how phytonutrients could help prevent disease and improve our health and well-being, eating a variety of phytonutrient-rich foods is part of having a balanced diet.

These foods have the highest total phytonutrient content:

Here are some ideas to include more of these foods in your meals and snacks:

  1. buy a new herb or spice next time you’re at the supermarket — and use them in cooking regularly
  2. try a spiced fruit compote. Simmer a mix of fresh, canned, dried or frozen fruit, including apples, peaches, apricots, or mixed berries with spices such as cinnamon, ginger, cloves or star anise. Store in the fridge and spoon over cereal or yoghurt
  3. make a spice base by browning chopped onions in a frying pan with a splash of olive oil, crushed garlic and a teaspoon of dried herbs such as cumin, caraway, oregano, thyme or marjoram. Add to soups, sauces and casseroles
  4. finely chop peppermint, spearmint or parsley and add to cooked peas, mashed potato and salads.

Your menstrual cycle and exercise. What you need to know.

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From energy levels to metabolism: understanding your menstrual cycle can be key to achieving exercise goals

It’s pretty normal to feel full of energy for exercise some days, and as though you can’t be bothered on other days.

For women, there’s a physiological explanation behind this. While men’s hormone levels do change over a lifetime, day-to-day they remain quite stable. Women, however, experience fluctuating levels of sex hormones daily.

Scientists haven’t yet worked out the complete picture when it comes to how the menstrual cycle affects exercise. But we know different phases of the menstrual cycle, due to the fluctuation of hormones, can affect metabolism and recovery from exercise, particularly for women participating in endurance activities.

Understanding the rise and fall of hormones during the menstrual cycle can allow women to adapt their exercise routines, and optimise their chances of succeeding with any training or weight loss goals they may have.

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The follicular phase: low hormones

A woman’s cycle, which is generally 28 days, can be broken up into two main stages: the follicular and luteal phases.

The follicular phase — days 1 to 14 — starts on the first day of a woman’s period. During this phase, levels of oestrogen (the primary female sex hormone) progressively increase and progesterone (the other female sex hormone released from the ovaries, which stimulates the uterus to prepare for pregnancy) stays stable.

At this time, women are physiologically similar to men in their metabolism and recovery. Training will feel easier and you will recover more quickly than during the luteal phase, which we’ll get to shortly.


Read more: Childhood, adolescence, pregnancy, menopause, 75+: how your diet should change with each stage of life


This ease of training and speed of recovery become more pronounced during the later part of the follicular phase.

Around day 12, levels of oestrogen and another type of hormone, the luteinising hormone, surge, triggering ovulation. You’re likely to experience an increase in energy and strength at this time, allowing you to put even more effort into your workouts.

So the follicular phase, particularly at the end, is the time to train hard: to incorporate new exercises and train at higher intensities. This is particularly relevant for women trying to lose weight.

A woman crouched on the grass ties up her running shoe.
The first phase of a woman’s menstrual cycle, or the follicular phase, is the best time for high-intensity exercise. Shutterstock

The luteal phase: high hormones

The luteal phase represents the second half of a woman’s cycle.

During this phase progesterone levels peak, resulting in an increase in resting heart rate, and decreases in aerobic capacity and ability to tolerate heat. Exercise may feel like an uphill struggle and you will tire more quickly.

The body burns more fat during the luteal phase, as the peak in oestrogen and progesterone suppress gluconeogenesis (the making of sugar from protein and fat).

This increase in fat burning may seem like good news from a weight loss perspective, but it makes it harder for the body to access sugar. This means exercise will feel harder.

So during this phase, the focus should be on incorporating lower-intensity cardio and strength sessions, and active recovery sessions such as walking, yoga and stretching.


Read more: Period pain is impacting women at school, uni and work. Let’s be open about it


Progesterone also breaks down muscle, so you won’t enjoy the same gains from your workouts, and recovery is slower.

Finally, the hormonal changes during this phase result in a shift of fluid from your blood plasma to your cells, resulting in bloating or fluid retention. Coupled with pre-menstrual symptoms such as headaches and fatigue, exercise is likely to seem harder than usual, so it’s not a time to be smashing your goals.

A young woman lies on the couch clutching her stomach. Her facial expression indicates discomfort.
During the luteal phase, hormonal changes will often mean women don’t feel up to strenuous exercise. Shutterstock

At this time your metabolism peaks (an increase by 5-10% from the lowest point one week before ovulation), and so can your appetite. The best way to manage all of this is with exercise — just of the low-intensity variety.

Eating carbohydrates and protein within a couple of hours of exercise also helps as it reduces your reliance on making glucose from other sources. This results in increased energy levels and quicker recovery.

You could try chopped fruit with 100% nut butter, some wholegrain bread with 100% fruit spread, or a serve of dairy, such as yoghurt.

And make sure to surround yourself with plenty of foods naturally high in sugar and fat — such as fruit, avocado, nuts and seeds. These foods release the same pleasure response in the brain as the processed and packaged foods you might be craving.

Tracking your cycle

It seems counter-intuitive, but when your period starts, you will start to feel normal again, as hormone levels return to baseline.

A well-planned food and exercise program will allow you to work with your cycle, not against it. This is worth thinking about even if you don’t usually experience menstrual symptoms — these hormonal changes are happening in your body regardless.

Start by tracking your menstrual cycle. Circle the first and last days of your period and count the days between the first days of two consecutive periods to determine cycle length. Or you might choose to use an app.

By recognising these phases of the menstrual cycle, women are better placed to deal with common pre-menstrual symptoms, and achieve their health, training and weight loss goals

The rise of ultra-processed foods and why they’re really bad for our health

The rise of ultra-processed foods and why they’re really bad for our health

Humans (and our ancestors) have been processing food for at least 1.8 million years. Roasting, drying, grinding and other techniques made food more nutritious, durable and tasty. This helped our ancestors to colonise diverse habitats, and then develop settlements and civilisations.

Many traditional foods used in cooking today are processed in some way, such as grains, cheeses, dried fish and fermented vegetables. Processing itself is not the problem.

Only much more recently has a different type of food processing emerged: one that is more extensive, and uses new chemical and physical techniques. This is called ultra-processing, and the resulting products ultra-processed foods.

To make these foods, cheap ingredients such as starches, vegetable oils and sugars, are combined with cosmetic additives like colours, flavours and emulsifiers. Think sugary drinks, confectionery, mass-produced breads, snack foods, sweetened dairy products and frozen desserts.

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Unfortunately, these foods are terrible for our health. And we’re eating more of them than ever before, partially because of aggressive marketing and lobbying by “Big Food”.

Ultra-processed foods are harming our health

So concludes our recent literature review. We found that more ultra-processed foods in the diet associates with higher risks of obesity, heart disease and stroke, type-2 diabetes, cancer, frailty, depression and death.

These harms can be caused by the foods’ poor nutritional profile, as many are high in added sugars, salt and trans-fats. Also, if you tend to eat more ultra-processed foods, it means you probably eat fewer fresh and less-processed foods.

Used plastic soft drink bottles
Put simply, ultra-processed foods are bad for our health and the environment. Igor Sefr/AP/AAP

Industrial processing itself can also be harmful. For example, certain food additives can disrupt our gut bacteria and trigger inflammation, while plasticisers in packaging can interfere with our hormonal system.

Certain features of ultra-processed foods also promote over-consumption. Product flavours, aromas and mouthfeel are designed to make these foods ultra-tasty, and perhaps even addictive.

Ultra-processed foods also harm the environment. For example, food packaging generates much of the plastic waste that enters marine ecosystems.

And yet, we’re eating more and more of them

In our latest study, published in August, we found ultra-processed food sales are booming nearly everywhere in the world.

Sales are highest in rich countries like Australia, the United States and Canada. They are rising rapidly in middle-income countries like China, South Africa and Brazil, which are highly populated. The scale of dietary change and harms to health are therefore likely immense.

‘Big Food’ is driving consumption

We also asked: what explains the global rise in ultra-processed food sales? Growing incomes, more people living in cities, and working families seeking convenience are a few factors that contribute.

However, it’s also clear “Big Food” corporations are driving ultra-processed food consumption globally — think Coca-Cola, Nestlé and McDonald’s. Sales growth is lower in countries where such corporations have a limited presence.

A huge coca cola advertising billboard
Aggressive marketing campaigns by Big Food companies are contributing to growing consumption of ultra-processed foods. Shutterstock

Globalisation has allowed these corporations to make huge investments in their overseas operations. The Coca-Cola System, for example, now includes 900 bottling plants worldwide, distributing 2 billion servings every day.

As Big Food globalises, their advertising and promotion becomes widespread. New digital technologies, such as gaming, are used to target children. By collecting large amounts of personal data online, companies can even target their advertising at us as individuals.

Supermarkets are now spreading throughout the developing world, provisioning ultra-processed foods at scale, and at low prices. Where supermarkets don’t exist, other distribution strategies are used. For example, Nestlé uses its “door-to-door” salesforce to reach thousands of poor households in Brazil’s urban slums.

Rising consumption also reflects Big Food’s political power to undermine public health policies. This includes lobbying policymakers, making political donations, funding favourable research, and partnerships with community organisations.


Read more: Sweet power: the politics of sugar, sugary drinks and poor nutrition in Australia


Here’s how things can change

The evidence that ultra-processed foods are harming our health and the planet is clear. We must now consider using a variety of strategies to decrease consumption. This includes adopting new laws and regulations, for example by using taxation, marketing restrictions and removing these products from schools.

We cannot rely on industry-preferred responses such as product reformulation alone. After all, reformulated ultra-processed foods are usually still ultra-processed.

Further, simply telling individuals to “be more responsible” is unlikely to work, when Big Food spends billions every year marketing unhealthy products to undermine that responsibility.

Should dietary guidelines now strongly advise people to avoid ultra-processed foods? Brazil and other Latin American countries are already doing this.

And for us as individuals the advice is simple — avoid ultra-processed foods altogether.

Myths about back pain that make it worse

Myths about back pain that make it worse

Kathryn O’Connell|September 16, 2020

Is your sedentary time racking up during the pandemic? Spending more time on Zoom calls? More time catching up on Netflix series? Less time exercising? Then you might be one of nearly 65 million American adults who has experienced a recent episode of back pain.

myths of back pain

Activity, not rest, is often the best treatment for back pain.

Back problems are among the most frequent complaints to doctors. They drive up healthcare costs by more than $12 billion annually, making back pain the sixth most costly condition in the United States. For 16 million adults—that’s 8% of the U.S. population—back pain is chronic and limits everyday activities.

How can we prevent or reduce back pain? After decades of research, the scientific community has found the answers, but they remain overshadowed by widely held myths and misconceptions. In this article, we explore three common myths surrounding back pain, and why people should consider what may initially seem counterintuitive to find relief.

Myth #1: Move less to reduce pain

What research says: James Rainville, MD, assistant professor of physical medicine and rehabilitation at Harvard Medical School, said that back pain is a natural part of aging, just like getting wrinkles and gray hair, and that there’s no evidence that being careful will slow the process.

But here’s where it gets tricky: Despite the fact that most cases of back pain are part of the deteriorative aging process, many also stop being painful over time without assistance. How? Dr. Rainville says it’s not because our backs become healthier or stronger (although that certainly helps, but more on that later), but because neurological healing processes are taking place. When a problem occurs that triggers pain, like a bulging disc or spine degeneration, the nervous system eventually adapts to the pain and eliminates the discomfort. Evidence suggests that more physical activity—not less—may actually help your nervous system adapt more rapidly and reduce discomfort overall.

One study noted that clinical practice guidelines endorse exercise therapy for persistent low back pain and recommend avoiding bed rest. The idea is that physical therapy slows muscle and tissue deterioration and improves function, helping prevent back issues from worsening. Along the same lines, too much rest promotes atrophy. Penn Medicine sports medicine physician Alexis Tingan, MD, recommends light aerobic activity, such as jogging, walking, or using a stationary bike, to reduce back pain, though he acknowledges that cases differ from person to person, and require careful coordination between patients, physicians, and physical therapists.

The takeaway: People suffering from common backaches and pains shouldn’t stop moving. In fact, they should find ways to safely add more movement into their day.

Myth #2: Avoid lifting heavy objects to save your back from further injury

What research says: Although moving an air conditioner or lifting heavy furniture can throw your back out, the truth is that only 5% of cases of new disc herniation and sciatica happen during heavy-duty physical activity. Most people experience new-onset back pain during simple tasks, like reaching for a pencil or bending over to brush their teeth, Dr. Rainville said.

That’s because back pain usually results from tissue failure caused by age-related deterioration. While lifting something heavy can be the straw that breaks your back, lighter exertion can also trigger back pain.

Fortunately, there’s a simple way to avoid (or at least delay) the deterioration that leads to most back pain: exercise. Most types of moderate exercise can help reduce back pain, but core-strengthening exercises may pack the most punch. A study of 30 patients with back pain found that core muscle strengthening exercise, along with lumbar flexibility and gluteus maximus strengthening, was an effective rehabilitation technique for patients with chronic low back pain, regardless of how long they’ve had pain.

According to Cleveland Clinic physical therapist Patti Mariano Kopasakis, PT, DPT, weak lower back muscles force the body to rely on passive structures for stability, like bones and ligaments, which causes pain. Stronger muscles help bear the load, reducing the likelihood of deterioration, injury, and pain.

The takeaway: Back pain is more likely to be caused by bodily deterioration than overexertion. Exercise is one of the best defenses.

Myth #3: Surgery is the best way to treat back pain

What research says: Surgery should be the last line of defense against back pain. Spinal fusion, one of the most common surgeries for back pain, can work for some, but it often fails to offer lasting relief, typically only reducing back pain by about 50% over a few years. “Based on the evidence, the indications for fusion are few and far between,” said Steven Atlas, MD, MPH, associate professor at Harvard Medical School, in an interview with Harvard Health Publishing. “But that doesn’t stop surgeons from doing them and patients from getting them.”

More conservative, non-invasive measures like exercise, physical therapy, heat/cold treatment, and good old-fashioned waiting-it-out can be just as, or more, effective, while reducing the risk of surgical complications. But these tactics tend to require a much longer commitment and, depending on insurance coverage, can be more expensive than surgery.

Some studies show that meditative approaches can be effective, too. In one study published in the Journal of Evidence-Based Integrative Medicine, researchers found that for almost 300 adults with chronic low back pain, an 8-week mind-body program modeled on Mindfulness-Based Stress Reduction (MBSR) significantly decreased long-term pain and increased short-term function.

The secret lies in tapping into the complex brain networks we use to process pain. “When engaged in mindfulness meditation, the networks that regulate pain are engaged and include the emotional, sensory, and cognitive networks, top-down pathways, as well as the parasympathetic network,” the authors wrote. “Mindfulness, therefore, engages a variety of pathways to regulate the experience of pain.

The takeaway: Surgery is not a cure-all for back pain and should be considered as a last resort for most people.

Busting the myths

Perhaps because back pain is so prevalent, myths cloud the reality of back pain’s big picture. Getting too much rest, avoiding physical exertion, and counting on surgery to solve problems we can usually fix ourselves may seem like reasonable tactics, but they’re actually harmful mistruths that make the burden of back pain much more severe.

The one trick to keeping a heart-healthy diet

Featured Articles in Internal Medicine In the News

The one trick to keeping a heart-healthy diet

Naveed Saleh, MD, MS, for MDLinx | April 30, 2020

For decades, the goal of a heart-healthy diet was to lower cholesterol. But it can be difficult to track the amount of cholesterol in various foods you eat. So, instead of focusing on a target number for dietary cholesterol, adopting dietary patterns that are naturally low in cholesterol may do the trick to keep a heart-healthy diet, according to the authors of a robust review of studies published in Circulation. https://tpc.googlesyndication.com/safeframe/1-0-37/html/container.html

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One simple approach can unlock a heart-healthy diet.

“A recommendation that gives a specific dietary cholesterol target within the context of food-based advice is challenging for clinicians and consumers to implement; hence, guidance focused on dietary patterns is more likely to improve diet quality and to promote cardiovascular health,” wrote the authors, who were on an American Heart Association (AHA) panel. 

“Dietary guidance should focus on healthy dietary patterns (eg, Mediterranean-style and DASH [Dietary Approaches to Stop Hypertension]–style diets) that are inherently relatively low in cholesterol,” the authors added. “These patterns emphasize fruits, vegetables, whole grains, lowfat or fat-free dairy products, lean protein sources, nuts, seeds, and liquid vegetable oils. 

AHA Findings

Per the authors of the review, an extensive corpus of high-quality evidence has produced mixed results regarding any link between dietary cholesterol intake and heart disease outcomes, including the risks of coronary heart disease, myocardial infarction, and stroke. For instance, a recent meta-analysis indicated that eating half an egg per day was linked to a 6% increase in the risk of heart disease. Other studies have also indicated a link between dietary cholesterol (ie, egg consumption) and heart disease—particularly among those with diabetes and risk of heart failure.

Data from interventional studies also show that dietary cholesterol has a modest effect on CVD risk factors and lipid and lipoprotein concentrations. “Our meta-regression analysis using data from controlled feeding studies, in which the ratio of polyunsaturated fatty acid to saturated fatty acid in the comparison diets was matched, indicated that dietary cholesterol significantly increased total cholesterol, but the findings were not significant for the stronger predictor of CVD risk, LDL cholesterol, or HDL cholesterol concentration,” the authors wrote.

Cholesterol levels

Notably, official guidelines—including Dietary Guidelines for Americans and the 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease—don’t give specific recommendations regarding cholesterol intake. The latter, for instance, more generally recommends that: “a diet containing reduced amounts of cholesterol and sodium can be beneficial to decrease atherosclerotic CVD risk.” 

The authors of the Circulation review pointed out that Mediterranean and DASH diets are low (<300 mg/d) in cholesterol. “Healthy dietary patterns are inherently relatively low in cholesterol, with typical levels similar to the current US intake,” they wrote. 

Per the 2013-2014 National Health and Nutrition Examination Surveys (NHANES), the average cholesterol intake in Americans aged ≥20 years was 293 mg/d (95% CI: 284–302). 

On the other hand, most high-cholesterol foods in American diets are also high in saturated fats. (Saturated fat accounts for more than 10% of calories in the average American diet.) 

“Because the majority of observational studies do not adjust for saturated, monounsaturated, and polyunsaturated fat, it can be difficult to distinguish between the independent effects of dietary cholesterol and dietary fat type.”

Although observational studies can’t provide this advice, other research can (as you’ll see below). 

Clinical practice

The authors make specific recommendations based on the results of their science advisory.

Due to the relatively high concentration of cholesterol in egg yolks, healthy individuals can include up to a whole egg or equivalent daily (eg, 3 ounces of shrimp). Furthermore, shrimp and other types of shellfish (which are relatively high in dietary cholesterol but very low in saturated fat) can be integrated into a heart-healthy dietary pattern when combined with lean or plant-based protein sources. 

Exceptions to this guidance include patients with dyslipidemia, especially those with diabetes or heart-failure risk, who should gingerly approach the intake of cholesterol-rich foods. On the other hand, older patients with cholesterol levels within normal limits can eat up to two eggs a day due to their convenience and nutritional benefits. Vegetarians may include increased amounts of dairy and eggs. 

In addition, replacing saturated fats with unsaturated fats will lower LDL cholesterol concentrations better than reducing dietary cholesterol alone, the authors advised. 

“For example, replacing full-fat milk with fat-free milk would lower saturated intake by 4.3 g/1 cup; however, this replacement would yield only a 19-mg reduction in dietary cholesterol. Replacing 3 oz lean ground beef with 3 oz chicken breast would lower saturated fat by 4.84 g but dietary cholesterol by only 3 mg,” they wrote. 

To be sure, the idea of evaluating your diet in more general terms is nothing new. Nearly 25 years ago, the term intuitive eating was first coined. This practice involves rejecting the idea of “dieting” and rigidly counting calories in favor of eating when you’re hungry and stopping when you’re full.

My Bioidentical Hormone Creams Are Killing Me !

I am still having to continuously defend myself against accusations from other doctors and professional groups about prescribing Bioidentical (Natural) HRT. This article from Dr Dach, an American doctor who has a similar practice to myself, shows that they are having the same problems. This article will provide you with some of the information you need to defend your use of BHRT when doctors try to get you to stop using them.

My Bioidentical Hormone Creams Are Killing Me !

My Bioidentical Hormone Creams Are Killing Me !!!

by Jeffrey Dach MD

With the publication of the NASEM report July, 2020, I was astonished to learn that for the past 20 years, compounded bioidentical hormones have been killing every one.(1)   If only we had used FDA approved hormone pills and patches manufactured by the Pharmaceutical Industry, everything could have been so much better.

This is All Nonsense

Of course, this is all nonsense, because over the past 20 years of prescribing compounded bio-identical hormones to thousands of patients, I can attest to good outcomes in patients on compounded bioidentical hormones, with relief of menopausal symptoms and good quality of life (QOL).  Of course, adverse side effects can occur, most commonly related to excess hormone dosage.   These are easily managed by adjusting dosage under the supervision of a knowledgeable physician.  .

Evidence Does Not Support Clinical Utility of Compounded Bioidentical Hormones

Here is the conclusion of the NASEM Report:

“Evidence does not support the clinical utility of compounded bioidentical hormone therapies and their use should be limited to patients who cannot use products approved by the US Food and Drug Administration (FDA),” (1)

Endocrine Nonsense Society ?

This NASEM report reminds me of the last time this came up in 2016 when the Endocrine Society advised doctors against using compounded bioidentical hormones.  Four years ago, I wrote an article suggesting the organization should change their name to the “Endocrine Nonsense Society”.  Similarly, NASEM which stands for National Academy of Science Engineering and Medicine should change its name to the ” National Academy of Nonsense, Engineering and Medicine“.(2)

Compounded Bioidentical Hormones Are on the Chopping Block

The Drug Industry has a long history using unethical and illegal activities including “dirty tricks” to advance its financial interests.  Indeed, the Drug industry has paid out 35 Billion Dollars in penalties for Criminal and Civil Violations.  One of the “dirty tricks’ over the years is the seeding of medical literature with “Ghost Written” articles disparaging bioidentical hormones and promoting their own patented synthetic hormones.(5-7)

Pharmaceutical Industry as Organized Crime Syndicate

Books by two eminent physicians Drs. Peter Gotsche, and Marcia Angell have documented the enormous corruption of the Pharmaceutical industry.  Dr. Peter Gotsche has gone so far as to compare the Pharmaceutical Industry with an organized crime cartel which has captured our legislative bodies, regulatory agencies, medical societies, medical  meetings, medical research, and the mainstream media, thus wielding enormous power over our society. (5-7)

Insidious New Campaign to Eliminate Compounded Hormones

With the publication of the NASEM Report, the Pharmaceutical Industry has launched an insidious new campaign to eliminate compounded bioidentical hormones.  This campaign is based on the NASEM report claim that only randomized placebo controlled trials represent “medical evidence”.  The FDA, an agency captured by the drug industry, funded a report by the NASEM (National Academy of Science Engineering and Medicine) to come up with the predestined conclusion:  Since there is no evidence for efficacy or safety for bioidentical hormones, therefore bioidentical hormones should be placed on the FDA “Difficult to Compound List”, a regulatory move which essentially bans compounded bioidentical hormones, eliminating a major economic competitor.  It’s just business. Two consequences will be:

1) Post Menopausal women will have no access to the compounded hormone creams they are currently using.
2) Compounding pharmacies across the nation will go out of business.

The Old Gimmick Used by the Pharmaceutical Industry

The basis for the FDA funded NASEM report is an old gimmick used over and over again by the drug industry to eliminate competing natural substances, and thereby gain market share.  According to patent law, natural substances such a bioidentical hormones can not be patented, so there is no money for expensive clinical trials.

The Only Acceptable Evidence

The old gimmick is to “declare” that the only acceptable “evidence” is the randomized double blind placebo controlled drug trial of the the type required for FDA new drug approval.  Although the Randomized Double Blind Placebo Controlled Trial is considered the gold standard for FDA drug approval, this type of drug trial is not practical for natural substances which can not be patented, nor for Off-Label drug use.  The reason patent protection is required is the cost involved in a randomized trial is prohibitively expensive in the range of 100 to 250 million dollars. No drug company in their right mind would incur this expense without patent protection to guarantee profits on the back end.  The same is true for most Off-Label drug use, usually involving Off-Patent drugs, meaning these are old drugs with expired patents.

Using a False Claim to Defeat the Competition

To make the claim that the only acceptable “evidence” is a randomized placebo controlled drug trial is not only false, it is standard gimmick or ploy used by the pharmaceutical industry for decades.  Off-Label prescribing is in the same boat, since there are no randomized placebo controlled trials to support Off Label use of an old drug. So, such an attack on compounded hormone preparations is also an attack on Off-Label prescribing, comprising 20% of all presciptions

The Privilege of Off-Label Prescribing

New drugs are FDA approved for a specific “indication”, a medical condition placed on the drug label.  However, about twenty percent (one fifth) of all drug prescriptions are prescribed Off Label.(1)  This means the drug is prescribed for a different indication unrelated to the original FDA approval.

Prescribing an Antibiotic for Cancer Off-Label

An example of “Off-Label” use is the prescribing of Clarithromycin for Multiple Myeloma by Dr. Tomer Mark of Cornell as a repurposed anti-cancer drug for Multiple Myeloma.  Clarithromycin’s original FDA approved indication is an antibiotic to treat bacterial infection, not as a repurposed anti-cancer drug. (3-4)

This common medical practice of “Off-Label Use” of a drug has always been accepted by all medical societies and regulatory agencies as a prerogative and privilege of the prescribing physician.  Since twenty percent of prescriptions are not based on a randomized double blind placebo controlled trial (typically used for FDA new drug approval), the next obvious question is: What other types evidence are used to justify Off-Label prescribing of drugs?

Other Types of Evidence for Prescribing Drugs Off Label

Doctors rely on many other types of evidence such as in-vitro and in-vivo animal studies, human observational trials, and registry trials.  Another powerful and highly accepted type of medical evidence called challenge, rechallenge, which proves drug causality.  Challenge-Rechallenge is accepted by medical science as well as our legal system (a court of law), and is used in medical research to show causality of a drug or treatment.

Of course, the doctor must understand the physiology, the basic science  showing the mechanism of action of the drug.  The importance of this cannot be over-emphasized, as it provides confidence that the drug is effective and can be used, or ineffective and should not be used.

NASEM Committee Rejects All Other Types of Medical Evidence

All of these other perfectly valid types of medical evidence have been rejected by the esteemed doctors of the NASEM committee who came to their ridiculous conclusion, that there is no evidence of clinical utility of compounded bioidentical hormones.  Needless to say this amounts to a form of scientific deception and fraud which, in a free society, should not be tolerated.   This erosion of scientific integrity is real, and if unchecked by a grass roots movement of enraged post-menopausal women, this insidious campaign against compounded hormone replacement is likely to prevail, resulting in catastrophic consequences for millions of post menopausal women, and their compounding pharmacies..

FDA Approved Bioidentical Hormones Preparations:

All the hormones used in compounded preparations have been FDA approved and are used OFF-Label in compounded preparations.  Here is a partial list of FDA approved hormone preparations for Estradiol, Progesterone and Testosterone:

Hormone Product    Year of FDA Approval     Manufacturer
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Alora (estradiol): FDA approved 1996 Watson Labs
Climara (estradiol): FDA approved 1994 Bayer
FemPatch : (estradiol) FDA approved 1997 Parke Davis
Vivelle-Dot (estradiol): FDA approved 1994 Novartis
Estraderm: (estradiol) FDA approved 1986 Novartis
Esclim: (estradiol) FDA approved 1998 Women’s First Healthcare
Estrace (estradiol): FDA approved 1993 Bristol Myers Squibb
Estring: (estradiol) FDA approved 1996 Pharmacia UpJohn
Prometrium (progesterone): FDA approved 1998 Solvay Pharmaceuticals
Crinone: (progesterone) FDA approved 1997 Columbia Labs
AndroGel (testosterone): FDA approved 1999 Unimed / Abbott
Testim (testosterone): FDA approved 2002 Auxilium

Compounded Bioidentical Hormones Are a Form of OFF-Label Use

As you can see with the above chart, the bioidentical hormones, Estradiol, Progesterone and Testosterone have all been FDA approved for specific indications on the basis of randomized placebo controlled trials.  Off-Label use of these drugs and other drugs is a common physician practice.  Compounded formulations of combinations of these three hormones is a form of Off-Label use and as such, the NASEM report requirement of placebo controlled randomized trial for each compounded formulation is a ridiculous proposal, and in fact is has never been required in the history of medicine for OFF-Label prescribing by a physician.

Medical Evidence Supporting Off Label Use of Bioidentical Hormones

The next obvious question is where is all this medical evidence excluded by the NASEM Report supporting the clinical utility, safety and efficacy of bioidentical hormones for Off Label prescribing ?  This evidence is abundant in the medical literature.  For starters, I refer the reader to two excellent review articles by Drs. Kent Holtorf, Erika Schwartz and David Brownstein. (8-9)  There are  many others.(10-18)  A Google Scholar search for the key words, “bioidentical hormones” yields 5,200 articles in the scientific literature.  Go take a look.

Here are two of my articles on the safety and efficacy of bioidentical hormones:

The Safety of Bioidentical Hormones

The Importance of Bioidentical Hormones

Hormone Replacement is Not a Stand Alone Program

The one pill, one clinical trial, one FDA indication mentality of the drug industry is inadequate for the complexities of actual clinical practice prescribing bioidentical hormones for the typical post menopausal patient.   A Bioidentical Hormone Program should not be considered a stand alone medical intervention.  A more holistic, integrative approach is required to achieve the best results.    A complete patient evaluation which addresses micro-nutrient deficiencies, thyroid function, and gluten sensitivity is included in the program.  I would recommend adding a cancer prevention program, as well,  with testing for and supplementation with Iodine, vitamin D3, Selenium and DIM (Di-Indole Methane).

Subservience to the Pharmaceutical Industry

In most of the NASEM Reports, subservience to the pharmaceutical industry agenda is not so obvious. This one is very blatant.  This NASEM  “Decree” reminds me of a scene in a Woody Allen movie, “Bananas”.   The little island of San Marcos has a new Dictator, and his first proclamation is: “All subjects are to wear their underwear on the outside”. Oh well, Just another day for George Orwell’s “Ministry of Health and Truth”. America, it’s a Great Country..(3)  See video below:

Conclusion:

In the 1940’s an obscure Penn State chemist by the name of  Russell Marker devised the Marker Degradation Process which opened the door for manufacturing bioidentical hormones inexpensively in large volumes.  Russell Marker gave this “Process” as a gift to the world, declining to obtain a patent for his chemical formulation.  Since the 1940’s, bioidentical hormones have been prescribed by physicians for the betterment of human life, specifically to relieve post-menopausal symptoms.  The FDA is seeking to change that by using a fraudulent NASEM report to ban the use of compounded bioidentical hormones.  This is the most evil, despicable thing I have seen in a long time. Where is the outrage?

Jeffrey Dach MD
7450 Griffin Road Suite 180/190
Davie, Florida 33314
telephone 954-792-4663
www.jeffreydachmd.com

Articles with Related Interest:
Click Here for Bioidentical Hormone Articles by Jeffrey Dach MD

Links and references

1) National Academies of Sciences, Engineering, and Medicine. 2020. The Clinical Utility of Compounded Bioidentical Hormone Therapy: A Review of Safety, Effectiveness, and Use. Washington, DC: The National Academies Press. https://doi.org/10.17226/25791.

2) Santoro, Nanette, et al. “Compounded Bioidentical Hormones in Endocrinology Practice: An Endocrine Society Scientific Statement.” The Journal of Clinical Endocrinology & Metabolism 101.4 (2016): 1318-1343.  Nanette Santoro, Glenn D. Braunstein, Cherie L. Butts, Kathryn A. Martin, Michael McDermott, and JoAnn V. Pinkerton

3) Mark, Tomer M., and Morton Coleman. “It’s time to take clarithromycin seriously in multiple myeloma.” Acta haematologica 135.2 (2016): 101-102.

4) Mark, Tomer M., et al. “Phase 2 study of clarithromycin, pomalidomide, and dexamethasone in relapsed or refractory multiple myeloma.” Blood advances 3.4 (2019): 603-611.

5) Fugh-Berman, Adriane J. “The haunting of medical journals: how ghostwriting sold “HRT”.” PLoS Med 7.9 (2010): e1000335. The haunting of medical journals how ghostwriting sold HRT Fugh-Berman Adriane J PLoS Med 2010

6) Angell, Marcia. The truth about the drug companies: How they deceive us and what to do about it. Random House Incorporated, 2005.
“The combined profits for the ten drug companies in the Fortune 500 ($35.9 billion) were more than the profits for all the other 490 businesses put together ($33.7 billion) [in 2002]. Over the past two decades the pharmaceutical industry has moved very far from its original high purpose of discovering and producing useful new drugs. Now primarily a marketing machine to sell drugs of dubious benefit, this industry uses its wealth and power to co-opt every institution that might stand in its way, including the US Congress, the FDA, academic medical centers, and the medical profession itself.”

7) Gøtzsche, Peter. “Deadly medicines and organised crime.” How Big Pharma has corrupted healthcare. London: Radcliffe (2013).
PRESCRIPTION DRUGS ARE THE THIRD LEADING CAUSE OF DEATH AFTER HEART DISEASE AND CANCER. In his latest ground-breaking book, Peter C Gotzsche exposes the pharmaceutical industries and their charade of fraudulent behaviour, both in research and marketing where the morally repugnant disregard for human lives is the norm.

The research literature is distorted by scientific misconduct through trials with flawed designs and analysis, selective publication of trials and data, and ghostwritten papers.

The author states on page 39, “Almost every type of person who can affect the interests of the industry has been bribed: doctors, hospital administrators, cabinet ministers, health inspectors, customs officers, tax assessors, drug registration officials, factory inspectors, pricing officials, and political parties.”

8) Schwartz, Erika T., and Kent Holtorf. “Hormones in wellness and disease prevention: common practices, current state of the evidence, and questions for the future.” Primary Care: Clinics in Office Practice 35.4 (2008): 669-705.

9) Holtorf, Kent. “The bioidentical hormone debate: are bioidentical hormones (estradiol, estriol, and progesterone) safer or more efficacious than commonly used synthetic versions in hormone replacement therapy?.” Postgraduate medicine 121.1 (2009): 73-85.

10) Ruiz, Andres D., et al. “Effectiveness of compounded bioidentical hormone replacement therapy: an observational cohort study.” BMC women’s health 11.1 (2011): 27.
This study demonstrates that compounded BHRT improves mood symptoms. Larger studies are needed to examine the impact on vasomotor symptoms, myocardial infarction and breast cancer.

11) Martins, Vera, et al. “Compounded bioidentical HRT improves quality of life and reduces menopausal symptoms.” Journal of Prescribing Practice 2.7 (2020): 384-390.

12) De Lignieres, B., et al. “Combined hormone replacement therapy and risk of breast cancer in a French cohort study of 3175 women.” Climacteric 5.4 (2002): 332-340.

13) De Lignieres, B. “Effects of progestogens on the postmenopausal breast.” Climacteric 5.3 (2002): 229-235.

14) Fournier, Agnes, et al. “Breast cancer risk in relation to different types of hormone replacement therapy in the E3N‐EPIC cohort.” International journal of cancer 114.3 (2005): 448-454.

15) Wood, Charles E., et al. “Effects of estradiol with micronized progesterone or medroxyprogesterone acetate on risk markers for breast cancer in postmenopausal monkeys.” Breast cancer research and treatment 101.2 (2007): 125-134.
These findings suggest that oral micronized progesterone has a more favorable effect on risk biomarkers for postmenopausal breast cancer than medroxyprogesterone acetate.

16) Hargrove, Joel T., et al. “Menopausal hormone replacement therapy with continuous daily oral micronized estradiol and progesterone.” Obstetrics and gynecology 73.4 (1989): 606-612.

17) L’Hermite, M. “Custom-compounded bioidentical hormone therapy: why so popular despite potential harm? The case against routine use.” Climacteric 20.3 (2017): 205-211.
HT can be optimized by continuously combining transdermal estradiol with progesterone (when required).

18) Thompson, Jennifer Jo, Cheryl Ritenbaugh, and Mark Nichter. “Why women choose compounded bioidentical hormone therapy: lessons from a qualitative study of menopausal decision-making.” BMC Women’s Health 17.1 (2017): 97.
This study finds that women draw upon a range of “push” and “pull” motivations in their decision to use CBHT. Importantly, we find that women are not only seeking alternatives to conventional pharmaceuticals, but alternatives to conventional care where their menopausal experience is solicited, their treatment goals are heard, and they are engaged as agents in managing their own menopause. The significance of this finding goes beyond understanding why women choose CBHT. Women making menopause treatment decisions of all kinds would benefit from greater shared decision-making in the clinical context in which they are explicitly invited to share their experiences, priorities, and preferences. This would also provide an opportunity for clinicians to discuss the pros and cons of conventional HT, CBHT, and other approaches to managing menopause.

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FDA: Bioidenticals are “Public Health Concern;” Ban Likely July 9, 2020

FDA Turns Its Back on Women July 23, 2020 Category: War On Natural Medicine

FDA Rigs Process Against Estriol, Other Bioidenticals
November 7, 2019

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https://a4pc.org/APC/Advocacy/Federal-advocacy/NASEM-cBHT.aspx

APC is still reviewing the report, but a few preliminary points are worth noting:

The NASEM study committee was populated by esteemed healthcare professionals, but there was not a pharmacist with patient-facing experience, much less a pharmacy compounder, in their number. Neither was there a physician with substantive experience in bioidentical hormone therapy. Likewise, the peer reviewers for the study included few compounders — but did include one former FDA employee (and current FDA contractor) who is a long-time, well-known opponent of pharmacy compounding.
Although compounded drugs are exempt from the new drug approval process because they are prepared to meet individual patient needs, the foundation of NASEM’s analysis seems to focus on the absence of new-drug-caliber studies of compounded meds. The report makes an illogical leap by effectively deeming cBHT unsafe unless it can mirror drug manufacturing in terms of safety and effectiveness data, labeling, AE reporting, pharmacokinetic data, and scale of clinical trials.
NASEM said it based its recommendations in large part on a review of literature, but identifies only 13 studies as having, in the judgment of the committee, suitable “rigor and relevance” — these, out of literally hundreds of studies out there, not to mention abundant patient outcomes data that could and should have been considered and weighed.
The report calls for restricting use of cBHT to patients with allergies to FDA-approved drugs, despite the fact that many FDA-approved therapies may not meet the dosing needs of patients — a point not addressed by the report’s recommendations.
The recommendations seem to suggest that a prescriber’s medical judgment and a patient’s preferences should play no role in determining a proper course of treatment — a stunning assertion that is applied to no other aspect of medicine or pharmacy care. Women’s needs are much more complex than the cookie-cutter approach offered by current FDA-approved drugs. Individualized therapy is the result of a balanced approach between prescriber, patient and pharmacist assessing each patient’s unique needs.
The NASEM study seems to suggest that states that do not adopt USP <795> and <797> chapters in whole, without question or amendment, are somehow under-regulating compounders, yet it provides no evidence of patient harm that has resulted in states that adhere to different standards.
The report cites concerns over bioavailability. However, many compounders or prescribers perform saliva or serum testing to confirm cBHT is appropriate therapy. Yet how many prescribers routinely check levels of FDA-approved products?
The report sends mixed messages. Individualized therapy is a part of FDA’s newly established goal of creating personalized therapies to target each patient. Factors such as age, weight, genetics, past medical history all contribute to appropriate treatment and dosage selection. Yet these NASEM recommendations seem to assert that FDA-approved drugs are always superior to compounded therapies.

The following drug products were withdrawn or removed from the market because such drug products or components of such drug products have been found to be unsafe or not effective. The following drug products may not be compounded under the exemptions provided by section 503A(a) or section 503B(a) of the Federal Food, Drug, and Cosmetic Act:

https://casetext.com/regulation/code-of-federal-regulations/title-21-food-and-drugs/chapter-i-food-and-drug-administration-department-of-health-and-human-services-continued/subchapter-c-drugs-general/part-216-human-drug-compounding/subpart-b-compounded-drug-products/21624-drug-products-withdrawn-or-removed-from-the-market-for-reasons-of-safety-or-effectiveness