… Growing Older without aging
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November 3 1997

CyberHealth Index


  1. Programmed cell death in bone tissue after estrogen withdrawal
  2. A quick P.S. on weights training
  3. Paradoxes, paradoxes
  4. Dr. Zava on phytic acid
  5. Great Quotations: self-care as an act of love

Programmed cell death in bone tissue after estrogen withdrawal

One of the hottest topics in current biomedical research is apoptosis, or programmed cell death. Apoptosis is the equivalent of cellular suicide. The self-destruct sequence can be initiated when the cell is found by the body to be defective. It can also be initiated when the cell is found to be unnecessary, superfluous, as is often the case during fetal development. Or the process can be due to lack of proper chemical signals coming to the cell, instructing it what to do.

Hormones are an important part of this signaling system. They can act on the cell membrane, or they can penetrate into the nucleus and give instructions directly to the DNA. Devoid of such instructions, the cell is likely to self-destruct.

But sometimes it’s a hormone that gives the self-destruct signal to a cell. Estrogens, for instance, are known to promote osteoclast apoptosis (osteoclasts destroy old bone as part of the constant bone renewal). Another example is progesterone initiating the apoptosis of excess breast tissue.

Osteocytes are mature bone cells, derived from osteoblasts. They play a role in repair mechanisms, insuring correct micro-architecture, act as mechanosensors, and contribute to the balance between bone formation and resorption. Scientists suspect thatBONE FRAGILITY INDEPENDENT OF CALCIUM LOSS MAY BE DUE TO OSTEOCYTE LOSS. This loss can reach 75% by the eighth decade.

In Tomkinson’s study, the number of osteocytes was checked thanks to biopsies of the iliac (hip) bone obtained from six women undergoing Goserelin or Triptorelin treatment for endometriosis. This type of treatment results in the shutting down of the ovaries and consequent severe hypoestrogenia. The biopsies were performed both before the initiation of treatment and after six months of estrogen withdrawal. Tomkinson found a 374.9% average increase in the percentage of osteocytes demonstrating DNA breaks characteristic of apoptosis. Tomkinson stresses that this was not necrosis, as seen in osteoarthritis, where whole clusters of osteocytes die, but rather a scattered pattern of dead cells, again characteristic of apoptosis.

Women who were treated with biphosphonates in an attempt to preserve bone mass still experienced osteocyte apoptosis.

Tomkinson points out that some women become vulnerable to fractures not long after menopause, before any major loss of bone. He theorizes that this is due to the rapid loss of osteocytes. Without the osteocytes, bone becomes more fragile.

Researchers have long been puzzled by how quickly bones deteriorate without constant exposure to the right hormones. This study seems to have found one important clue about this process.


Tomkinson A et al. The death of osteocytes via apoptosis accompanies estrogen withdrawal in human bone. J Clin Endo Metab 1997; 82: 3128-35.)

P.S. Gail Peterson, our CH editorial assistant, has made these comments:

“I hope you will follow this up with an article discussing some of the research which has found estrogen therapy increases bone density. Most women believe that estrogen therapy can only maintain or retard bone loss, and that it cannot actually build bone.

One other thought about this piece: when the ovaries were shut down in the Tomkinson study you discuss, progesterone production was halted as well as estrogen production. But any possible role of progesterone loss is not addressed.”


  1. It was originally thought that all estrogens do is restrain the osteoclasts. Now we know that estrone stimulates the development of the osteoblasts (as well as myoblasts, which form muscle tissue). DHEA also plays a role; in bone, DHEA is aromatized to estrone. The dramatic aging-related decline in DHEA is seen by some as the main reason bone density begins to decrease long before menopause. Testosterone, easily aromatized to estradiol, no doubt also plays a role; in fact one study found free testosterone to be the best biomarker of postmenopausal spinal bone integrity. I see now that there is indeed a need to go over the recent PEPI results on bone density, and to review other studies as well.
  2. The role of progesterone in bone health continues to be a matter of controversy. It seems that most scientists are willing to grant progesterone at least a helping status, considering its ability to compete for receptors with bone-destroying glucocorticoid hormones and possibly also inhibit inflammatory cytokines. Gail’s question can be put this way: CAN PROGESTERONE PREVENT THE APOPTOSIS OF ESTROGEN-DEPRIVED OSTEOCYTES?

Someone will have to perform the right experiment, probably using ovariectomized animals. And we also need to test the effects of DHEA and testosterone on osteocytes; sufficient DHEA and/or testosterone might be enough to prevent osteocyte apoptosis. (Sorry to be summarizing all this without references—this is just a capsule preview of how complex things are.)

An unrelated thought: as I was reading about how much any cell’s function and even its continued existence depend on receiving constant signals from other cells, signals that tell the cell,”You are needed,” I pondered how each of us is like a cell in a larger social organism, and how much we depend on getting the right signals from others: verbally, through touch, smiles, etc. An infant can die if it doesn’t get enough cuddling. And the elderly? Do they get enough signals? Do they grow deaf in part because no one talks to them? Is there a kind of”social apoptosis”? Your comments are invited.


Women, alas, have only a fraction of the upper-body strength that men do. Hence weight training for women can’t be as aggressive as men’s muscle-building regimens. A woman should start very slowly: just a bit of baby weights until lifting those simply doesn’t feel like any significant resistance, and somewhat heavier weights now feel the way baby weights felt at first. Our muscles and ligaments have to build up slowly, without trauma. We don’t build muscles as easily as men do, nor do we repair them like young male athletes, either. So please, easy does it. Overdoing it, especially right at the start, means the risk of getting really sore, or even injured.

I’ve been told that one way to tell if you’re doing it right is this: exercise hard enough to hear yourself breathing, but not so hard that you have trouble breathing. Also, the old”no pain, no gain” rule is now criticized by a lot of experts. If it hurts, stop.

I find that having fun and seeing results is very important for me. The pectoral squeeze (see CH 1) is one of my favorite fun exercises, and it can be augmented with light weights.

When I told a male friend how much I like to do the pectoral squeeze, he said,”Oh, I do that with sixty-pound weights.” Well, I do that with two-pound weights—or none at all—and yes, even I get VISIBLE RESULTS, WITHOUT THE RISK OF INJURY. My exercise motto is:”Take baby steps, have fun, and persist.”

In addition, I caution against the weight-training hype that you see in some sports magazines. While some women are absolutely delighted with what weight lifting has done for them—building not just their muscles, but also their self-esteem—there are also women who’ve dropped out because they were pushed too hard, injured their shoulder joints, and/or for them it just wasn’t as much fun as, say, tennis. I think we need more”muscle studies,” including the measurements of bioelectric impulses that different types of exercise generate, apparently an important factor in muscle health. And this personal confession: I think it’s the swimmers and divers who develop the most graceful bodies.


Lynne writes:

The piece on Love/Cauley was great. I read it several times and got more out of it each time. There are so many paradoxes. The cadavers of the obese made a lot of sense in terms of musculature, which makes me think about weight in general and how little we know, especially with women.

Atkins has always held that heart disease is primarily an endocrine disorder, for example. And if cancer is primarily an endocrine disorder, so many of the recognized risk factors, which seem to be endocrine related, only exacerbate the problem. Do you think there is any such publication such as New Paradigms in Endocrine Theory? The LEF people seem to be pursuing that, as you pointed out.

Ahah! Wheat! I’ve been waiting for a reason to cut down or stop wheat. I’m so glad you published that. I think people believe that if wheat is everywhere, they can get away with eating it frequently. I really feel better, the less I eat of it.

Ivy replies:

One thing here is the political incorrectness of many research findings. For instance, it could be said that low wine consumption is a risk factor for heart disease. Should we be telling tea-totalers to take up drinking?

Or: something in male sweat makes women’s cycles more regular. Should we be telling men not to shower before a date? And, seriously, should we be telling women to please be at least mildly obese?

Could it be that the current”mean and lean” macho body ideal is being pushed on women in total disregard of the role of body fat in female hormonal health?

It’s much too early to make clear recommendations, and in the case of obesity, fatter may be better only up to a point, and only if the fat is in the right location (fat is like real estate: location is everything).

And location is governed by male/female hormone ratios (we’ll have more on how this works in an upcoming article). You want to avoid abdominal obesity, the dangerous kind. This is where Wilson was probably absolutely correct: do not let menopause virilize you. Stay”feminine forever” for the sake of your health.

It has long been suspected that a certain minimum amount of body fat is needed for female sexual maturation and fertility. Here is something of interest:”Researchers have spent years calculating the importance of waist-to-hip measurements in women, right down to the decimal points. The idea, basically, is that the perfect curve is engineered by the perfect amount of fat, which is roughly comparable to the amount of calories needed to make a healthy child (80,000). Men respond to women’s fat-padded curves because they signal reproductive health.” (Deborah Blum,”Sex on the Brain,” Penguin 1997, p.101)

Not seeing the hormonal aspect of heart disease when premeno/postmeno women are such an extreme illustration is medical blindness to the utmost. Of course INSULIN enters into the picture, as Atkins and Sears constantly point out, voices crying in the wilderness. DHEA also enters into the picture.

Cancer and DHEA—we’re learning more and more. Is cancer largely a DHEA-deficiency disease?

There are always the unsolvables, the genetic cases, various weird rare cancers and what not; but for maybe as much as 90% of the cancers we can point both to various carcinogens and to hormonal factors (which are always entangled in the larger picture: say, stress lowering DHEA; processed carbohydrates sending insulin through the roof).

What about the hormonal connections in depression and schizophrenia? But look, we don’t even fully understand PMS or the exact mechanism of hot flashes. No matter what type of serious illness we look at, there is always endocrine pathology. But which comes first? Sometimes it’s hard to tell.

Take the aging process itself, which scientists like Regelson regard as the ultimate, underlying disease, a sort of”mother of all degenerative diseases.” Do hormones decline because of aging, or does the hormonal decline lead to aging? Or is it both, in an ever-accelerating degenerative cascade?

As if this weren’t complicated enough, we also see that while some hormones decline, other hormones rise with age. Insulin and cortisol are two big trouble makers here. So we have deficiencies, excesses, imbalances.

I think we are beginning to see that the free-radical theory of aging (Harman) and the neuroendocrine theory of aging (Dilman) are not mutually exclusive, but rather complement each other. One of the most interesting articles in the Life Extension Magazine was Terri Mitchell’s”The Ageless Bird” (October 1996). The fulmar, a seabird that looks like a small seagull, maintains youthful levels of reproductive hormones and shows no signs of aging. But the article also points out that birds, whose maximum life span is three times that of captive mammals, have superb antioxidant defenses. Some hope that in the future human antioxidant enzymes can be boosted through gene therapy.

Antioxidants are regarded as the first wave of the anti-aging revolution.

Hormone replacement is the second wave. Manipulation of neurotransmitters (sometimes called”neurohormones”) may be the emerging third wave. We are doing all of this badly, but even doing it badly seems better than doing nothing.

I think it was Dr. Julian Whitaker who said that there is no fountain of youth, but there are many”rivulets of youth.” Clumsily, through trial-and-error, we are beginning to learn what they are.

About wheat: it’s also been my experience that the less wheat I eat, the better I feel. It would be fascinating to see if this holds true for the majority of people anywhere.

A while back, before I kept better track of references, I read somewhere that there is a wheat-eating region in the north of China, and those wheat eaters are not as healthy as the rice eaters. True, epidemiological studies are too confounded to prove anything, but it’s intriguing to speculate along the lines suggested by Jim Barron: possible immune suppression, and maybe mineral deficiencies caused by phytates—see Dr. David Zava’s post below.


David Zava, Ph.D. (Pharmacology), writes:

Phytic acid is present in many grains and legumes. Another name for it is inositol 6 phosphate. It’s a high energy storage form of phosphate for grains and legumes that is used during germination. Phytic acid plays havoc on minerals in your GI tract; it chelates many of the important minerals like zinc, copper, magnesium, iron, etc. There are many nutritionists who believe phytic acid is responsible for many diseases in third world countries because of its mineral-depleting properties in the GI tract. In most cultures of the world grains and legumes are fermented or soaked in water overnight to remove the phytic acid.

Of all the legumes, soybeans have one of the highest contents of phytic acid, which makes them potentially unhealthy if the beans are not prepared in their traditional manner—soaked (TOFU) and served with sea vegetables or fermented (Miso, Natto, Tempeh, etc). Fermentation of soybeans removes the anti-nutrients like phytic acid. It took the Asians about 2000 years before they started eating soybeans because they realized how toxic they were. Not until the advent of fermentation did the soybean become a staple of the Chinese diet.

In my opinion, women in America are making a big mistake focusing on phytic acid-rich soy junk food to help them with menopausal symptoms. Phytic acid wreaks havoc on zinc especially, a mineral needed for proper brain function and about 50 enzymes. Too much of the wrong kind of soyfoods, in my opinion, could be very unhealthy.

I have a chapter in the book I am co-authoring on Breast Cancer Prevention about soybeans. There is a section I call the dark side of soybeans that talks in more detail about the abundance of anti-nutrients in soybeans. You know what Ivy, this whole soybean issue is just being stuffed down women’s throats by the soy industry. Soy isn’t what it is being cracked up to be.

That’s what part of the soy chapter is all about. If a woman wants symptomatic relief she should just take estrogen, progesterone, and/or androgens. Wilson was almost right. He just got on the wrong track with synthetic progestins.

Ivy replies:

That last reference is to Dr. Robert Wilson, who started the menopause revolution with his book”Feminine Forever.” As seems true of all visionaries, he wasn’t right in all the details, but his main thesis about the anti-aging effects of hormone replacement is increasingly borne out by research. His notion that it should start earlier than menopause is probably on the right track also, though back then he had no idea about the decline in DHEA and testosterone, for instance, and how bone loss, muscle loss, and other degenerative changes begin already in the thirties.

Even if eating a huge amount of soy can bring a degree of symptomatic relief, there is no escaping the fact that human bodies evolved to run on human hormones, not plant hormones. (Make no mistake about it, Dr. S. Love is strongly in favor of hormone replacement; it’s just that she wants to replace human estrogens with plant estrogens.) I don’t doubt that phytoestrogens can be beneficial, especially once we do the dose-response studies and figure out the right intake. But I still see phytoestrogens more in a supporting role.

It strikes me as very strange that so many women assume their own hormones are”bad,” coming from a woman’s body, while plant estrogens must automatically be good since they come from plants.

As far as potency, it’s like comparing a mouse to a lion. But in large enough doses, phytohormones can have a significant impact, and we better have systematic research on that, since no doubt there are dose-dependent effects.

It’s also possible that the chief preventive effect of soy intake is prepubertal, when the breasts are just beginning to develop. The same may be true of exercise.

But this is a post on phytic acid, not phytoestrogens. I already said that the mass-produced yeast-raised bread is nothing like the leavened (fermented) bread our ancestors ate, calling it the stuff of life. I’m afraid that most of our bread is the stuff of disease.

And beware of soy products which are not prepared the traditional way.

Please note that Dr. Zava favors miso and tempeh—the naturally fermented products which have also been found to be the richest sources of genistein.

Soy milk is a poor source.

As always, I’m not telling you to take this as gospel truth; experiment, and listen to your body, as Lynne has been doing in regard to wheat. Don’t forget the principle of biochemical individuality (known for centuries as”one man’s meat is another man’s poison”). Neither Dr. Zava nor I nor anyone else can really tell you what type of food is best for you: only your body can tell you.

On a different note: I’m excited to hear that Dr. Zava is working on a book on breast cancer prevention. I think women are getting tired both of mainstream neglect of the overwhelming importance of prevention, and of the alternative health industry aggressive hype of whatever it is they are trying to sell, including outrageously priced soy candy bars. Women are tired of the for-profit games that are being played with their health and their lives, and are beginning to ask some hard questions. Note the title of Dr. Vliet’s book:”Screaming to be Heard.”


Elaine writes:

You mentioned about rice and some foods. I recently got a great book called Nourishing Traditions by Sally Fallon and Mary Enig. It’s called the politically incorrect book because of her stand on meat and dairy.

Basically the way it used to be years ago, not today. Raw milk and cream, organic meat and sprouted grains. She says canola oil is poison. It comes from rape seed oil which insects won’t even eat. She recommends coconut oil for baking and explains why.

Ms. Fallon also says lactose intolerance wasn’t a problem with raw milk, only after pasteurizing and homogenizing which alters the milk in such a way that it’s not good for anyone to use. She is also not a fan of soy. If you ever want to get into it, it’s a great book and is totally opposite of what we’re told today and even has recipes.

I just love it and it makes perfect sense to me. A lot of the diseases didn’t start until after the food processing started. When I think of some people today they way they eat – it’s scary. Some people probably don’t get one ounce of value from their food in a day, if they eat all processed foods and cooked to death foods.

Ivy replies:

Yes, it is scary. I want to emphasize Elaine’s statement:”A lot of diseases didn’t start until after the food processing started.” What breaks my heart is to see the way many kids eat. Childhood obesity is at an all-time high in this country — 25% of American children are obese, if I remember correctly (and 36% of American women;”obese” means at least 20% above desirable weight). Obviously nobody would feed junk food to farm animals, because that’s investment and farmers make money only if their animals stay healthy. When it comes to children,”our investment in the future,” we as a society don’t seem to care.


DICTOCRATS. It was written by Sally Fallon with Pat Connolly and Mary Enig, and is available in paperback from ProMotion Publishing, 800-231-1776. It explains various ways of eliminating or reducing phytic acid, among other things.

These authors may not necessarily be right about everything. Rapeseed oil has been safely used in the Orient for centuries. Still, why not use olive oil instead, with its proven benefits? Also, I’m not so sure about lactose intolerance having to do with milk processing. On the other hand, my grandmother always boiled milk; recently I read that this destroys a harmful enzyme. Not, mind you, that my grandmother could have possibly known that; she just did what her mother always did.

Where the authors are probably absolutely correct is in pointing out the value of traditional fermenting methods, and in stressing adequate fat intake, including the CLA-supplying animal fats (CLA is conjugated linoleic acid, an antioxidant and anti-carcinogen). And those fabulous natural broths! Ah, I’m beginning to drool remembering my grandmother’s soups. And beet soup—could it have something to do with the fact that she never even had colds?

I haven’t seen the book yet, but it does sound very interesting, and refreshingly politically incorrect. But remember: no expert is always right on every single detail, or can prescribe a diet that fits everyone’s biochemical individuality.


“To look good, look for good things about yourself. Dress and apply make-up as an act of love.”

Ivy: I also like what Marianne Williamson says about making the effort to look good as a gift to others.


The material contained herein is intended as information only, and not as medical advice.

California Age Management Institute ©