Bone Health
A Stimulating Interview with Takuo Fujita, M.D.
Dr. Takuo Fujita (1929-2022)
One of the great pioneers of basic and clinical bone and mineral research.
President, Osteoporosis Foundation of Japan Founder, Calcium Research Institute of Japan
Interview from June 1999
Click here for AUDIO transcript of this timeless interview
Dr. Fujita, please tell us about your background?
I am a physician, clinical investigator and radio technologist. I received my degree of Doctor of Medicine from the University of Tokyo in 1952. As a recipient of the Fulbright fellowship I continued my studies at the University of Buffalo from 1952 up to 1956. As one of the pioneers of calcium studies I studied calcium metabolism and bone disease at the University of Tokyo and Kobe` University.
Tell us of your current activities in calcium research?
I am the president of the Japan Osteoporosis Foundation and director of the Calcium Research institute so I am very active in every aspect of calcium studies, including patient studies and clinical investigations.
How many studies have you published on calcium?
Four hundred and twenty, all in peer review journals.
How long have you been researching calcium and [bone loss]?
About 46 years. I began in 1953 at the University of Buffalo Chronic Disease Research Institute. […]
What is [bone loss]? How serious is it?
Bone loss is weak, breakable, brittle bone, which occurs as a consequence of calcium loss from bone. Bone without calcium is very weak and if we don’t take enough calcium, or if we lose too much, our bodies become calcium deficient. Since 99% of calcium in the body is in the bone, bone is the first part of the body to be affected.
Why is [bone loss] often considered a woman’s [condition]?
Men also lose calcium, but women undergo a very dramatic event at the time of menopause. A sudden decrease in estrogen (female hormone) brings menstruation to an end and triggers a very rapid loss of bone-calcium. […] We all paid too much attention to this one event and we thought that post-menopausal [bone loss] was everything. That’s why for so long we considered [bone loss] a women’s condition. Certainly, it occurs more frequently in women, and earlier too. After the age of fifty, women are exposed to increased risk of [bone loss], whereas men reach an equivalent risk factor much later-maybe around age seventy. So the risks are delayed.
So as men live longer and longer, would you expect to see their [bone loss] risk approaching that of women?
Yes. One of the reasons that so many men don’t suffer from [bone loss] is that they die before women. I believe average life expectancy for American men is about seventy-three or seventy-four-it’s seventy-seven in Japan-but even among women the most severe forms of [bone loss] occur after age seventy-around seventy-five. So, men don’t have the same opportunity to suffer from [bone loss]. That is one reason. The other is the slow start of [bone loss] in males.
What is the role and importance of calcium in the human body?
Calcium is the fifth largest component of the human body after carbon, hydrogen, nitrogen and oxygen, the constituents of organic compounds. It is the most abundant mineral in the body. That makes it very important. Ninety-nine percent of calcium is in the bone, but the remaining one percent is distributed throughout the cells. In each cell and of course in blood there’s always some calcium, and this calcium outside the bone is even more important than the calcium that’s giving strength to the bone. All cells-hormone secreting cells, heart cells, liver cells, kidney cells and brain cells-need calcium to perform their functions. That’s why calcium is vital to human beings.
You've been conducting research on a special form of calcium. Can you tell us about it?
Not all calcium preparations are alike. Some are more easily absorbed than others. Generally speaking, calcium is one of the least absorbable compounds. For example: sugar. If you eat something sweet, almost 100% is absorbed immediately, including vitamins and other materials. But only 20% or so of the calcium you eat is absorbed. This is a very, very low figure-only one-fifth of what we eat! So we have to improve the absorption of calcium in order to really help the body to utilize calcium. We have had a recent breakthrough in the form of AAACa (U.S. brand name is AdvaCAL), which is quite absorbable, unlike all other calcium preparations. We make this by heating oyster shell in a vacuum, then adding some similarly treated algae to this. We call it HAI-Heated Algal Ingredient and this combination of oyster-shell calcium and Algal Ingredient makes it very absorbable.*
What are the greatest advantages of AAACa (AdvaCAL) over supplements like calcium citrate or calcium carbonate?
Well, some preparations are better than others. Calcium citrate is one of the better ones. Calcium carbonate is most commonly used but the body’s absorption of calcium carbonate is very poor, unless we have very strong stomach acid. That is why we recommend the use of calcium carbonate when you eat. Calcium contained in your food or taken with food is usually better absorbed than most calcium supplements alone. That’s because the gastric acid is released in response to the food. But AAACa is so readily soluble in water that it doesn’t even need gastric acid. Anybody can take it. Unless it is readily soluble in water, of course it doesn’t get into the blood. So one advantage of AAACa is high solubility. The second advantage is its high availability prompted by the algal ingredient.*
Tell us about your research on bone loss and bone mineral density as affected by AAACa versus other calcium supplements.
To show whether AAACa is really effective against [bone loss] we have to perform bone measurement. Now any studies which are not randomized or placebo-controlled are not considered valid these days, so I did all these procedures with a group of very elderly ladies-in their eighties. These ladies were deficient in calcium and calcium absorption. If we could demonstrate an effect in these ladies it would no doubt help others to have better absorption. So the challenge-the most difficult part first-was to choose a placebo that contains no calcium but which looks exactly like the calcium preparation so that these people didn’t actually know which was calcium and which wasn’t. Even the doctors were blind to the nature of the drug. That’s what we call a double-blind procedure. Neither the doctor nor the patient knows which is which. And we used calcium carbonate too, for a total of three groups-AAACa, calcium carbonate and placebo-for two years. It took quite a long time and some of these patients dropped out for various reasons. But a good number continued for the full twenty-four months and we found a very impressive increase in bone-mineral density (BMD) in those who received AAACa and a very significant fall of BMD in those who took placebo. Everybody is getting older and losing bone, so we expect such a loss. So even if we are able to merely sustain the BMD, that would be very interesting, but there was a significant increase in BMD for AAACa users. This was quite surprising. In fact, no other existing preparation has been able to produce a definite increase in BMD. Calcium carbonate, by the way, just about sustains BMD and is maybe slightly better than placebo, but can’t compare with AAACa.*
That clinical study was done with elderly patients-a very tough population. Have you studied pre-menopausal women?
Yes. We have studied middle aged women-around fifty to sixty. There are several ways to measure BMD. Some of them are more sensitive than others, so for this study on the middle-aged we have chosen the best and most sensitive measurement available-Peripheral Computer Tomography. This method is characterized by separate measurements for cortical (hard) and trabecular (spongy) bone. This spongy bone is more sensitive to the increase of calcium or other drugs because they have a more abundant blood supply, and are more elastic and changeable. By measuring spongy bone of the forearms we demonstrated a 3% increase of BMD. This was after only four months.*
How did you dose these patients in your study?
In all these studies we selected 900mg of elemental calcium a day for both AAACa and calcium carbonate.
You have developed a theory which you call the 'Calcium Paradox.' What exactly does it say?
It’s a paradox because we see the opposite of what we would expect. All of us are calcium deficient. I think everybody agrees with that. Everybody also agrees that when we are deficient in blood calcium, the bone will lose its calcium. Whole body calcium deficiency runs parallel to bone calcium deficiency. Calcium deficiency is a cause of [bone loss], though others may cite other causes-for example estrogen deficiency also contributes to calcium deficiency. We summarize by saying the cause of [bone loss] is calcium deficiency. But the paradoxical part occurs when the parathyroid hormone secretion increases in response to the blood calcium deficiency. The first important thing about calcium is that we should have an abundant supply to keep our bones strong. The next most important is its function in heart and brain action, and muscles. All these vital body functions are maintained by a constant abundance of calcium in the body. If we don’t keep calcium levels in the blood constant, the heart stops. Dr. Ringer of England demonstrated this many years ago and we still us Ringer’s calcium solutions. If you add calcium chloride to a saline (sodium chloride) solution, the heart will beat. Dr. Ringer demonstrated this with a frog’s heart. He removed the heart, put it in saline solution and the heart stopped. When he added calcium to the solution, the heart began to move. The fact that we need a constant amount of calcium is the beginning of the calcium paradox theory. We must keep our blood calcium constant but we don’t eat enough calcium. If this calcium deficiency were to bring down blood calcium, your heart would stop. That’s a terrible thing. Fortunately, it doesn’t stop because in response to even a very slight fall of blood calcium, the parathyroid hormone takes calcium out of the bone. Compared with the modest needs of the rest of the body, bone is an almost endless supply of calcium. It’s like a bank with a large amount of money. If you have a problem, you go to the bank and borrow. The parathyroid hormone is like a cash card. But if you use your cash card enough times, your bank account will become exhausted. That’s [bone loss]. And now the paradox begins. Calcium coming out of the bone enters other tissues where there shouldn’t be any calcium to begin with. For example, in the blood vessels. Blood vessels should be soft and elastic. Bones should be hard and strong. There shouldn’t be too much calcium in the blood vessels. They become hardened. […] This is the first calcium paradox [condition] which came to our attention. Deficiency of calcium results in flooding of calcium in the blood vessels. […]There are many other calcium paradox diseases[…].
So you’re saying that the parathyroid gland removes calcium from the bone at such a rate that our health is compromised?
Our body should be very wise. It shouldn’t make any mistakes. But in this instance I don’t know. Sometimes, it does strange things. Why does the parathyroid hormone take an excessive amount of calcium? Because there is so much calcium in the bones-ten thousand times more than we eat or have in our blood or soft tissue, so even our wise body doesn’t exactly do the best thing. That is one thing I don’t understand. But we have all the facts and the calcium paradox is only one attempt to explain all these facts. I don’t really have an answer.
All your studies so far have been done in Japan, but some people may be concerned that the Japanese diet is different from the North American diet. Would you expect to see similar results in a North American study group?
Well, the Japanese live very long. They have the highest longevity in the world. They say that fish and seaweed is good for them. The sushi bar is quite popular in this country. But the only trouble with the Japanese diet is that is is very low in calcium content. You are taking more calcium here in this country and in the Western world than in Japan. Other countries in Asia like Korea and China also have a very low calcium intake, so that may be one reason why calcium is so effective in Japan. But I think we can expect similar effects-maybe not the same but similar-in the United States, because many investigators in the United States also point out that even Americans are not taking enough calcium. In addition to the intake of calcium we have also to think of the loss of calcium. If you take large amounts of protein or phosphates-if you eat meat and all kinds of delicious foods you’re already taking a lot of phosphates and protein-and that will accelerate the loss of calcium in the urine. So we have to consider both sides-what you are taking and what you are losing. I’m afraid that although Americans are taking more calcium, they’re also losing more calcium. So I think we are almost equal. We are taking less calcium, but our calcium loss may also be lower, so i’d expect similar effects.
It’s important to note that you were giving your patients about 600mg of calcium a day with food. According to U.S, figures I’ve read, that’s about what the typical American receives.
That’s right. Actually calcium intake varies widely among different countries. Some people take enough calcium-mainly health-conscious people-but elderly people in most countries are not taking enough. Their appetite diminishes and they don’t feel right. And of course the problem of sunshine exposure is very important. Without sufficient exposure to sunlight, you can’t make enough Vitamin D to stimulate calcium absorption. Some people in the United States are also calcium deficient, like many Japanese, and I don’t think there’s too much difference in calcium intake.
In the United States, a calcium and magnesium complex is quite popular. How would you compare that compound with AAACa (AdvaCAL)?
Well, calcium and magnesium are both important but we don’t have to combine them. The ratio of calcium to magnesium is not important, as long as we are taking enough of both. Too much calcium intake is never dangerous, but too much magnesium can be. So I think calcium is the only one of which you can take as much as you want and get away with it, but you shouldn’t take too much magnesium. I don’t think we have to combine these two. You may take magnesium if it’s necessary. Too much calcium may constipate you-it’s one of the unavoidable effects of calcium because calcium takes water away from food and makes the stool harder. Magnesium doesn’t do that, so that’s why magnesium is used against constipation. I already use magnesium along with calcium, but not as a fixed preparation.*
AAACa is comprised of calcium hydroxide and calcium oxide, which you have mentioned are highly soluble in water. Can their high solubility produce any side effects or other problems?
Strangely, I encountered no side effects except maybe some constipation in some people. You may feel a little full in your stomach if you take large amount of calcium but it doesn’t mean that calcium decreases the appetite. Hyper-acidic people-who secrete more acid in the stomach-may tend to have ulcers, and calcium neutralizes gastric acid. But when calcium disappears from the stomach there may be a rebound of gastric acid secretion. It doesn’t happen in healthy people, only hyper-acidic people have this problem.*
If the parathyroid gland is clever enough to extract calcium from bone when it's necessary, why doesn't it regulate the amount it selects?
That’s a very good question, but I don’t really have an answer.
Are other factors involved, or is this purely the responsibility of the parathyroid?
The parathyroid is a very strange hormone. To begin with, there is no parathyroid in fish, but they live easily without it. They are continually inhaling calcium-rich water and have a non-stop supply of calcium. It only develops in creatures living on land, like ourselves. There might be some difference between constant increase in parathyroid hormone and occasional (periodic) increase. Now, is parathyroid hormone good or bad? It must be good because we need parathyroid hormone. But constantly high parathyroid hormone levels are not good. We have statistics showing that people with lower parathyroid hormone live longer and those with higher parathyroid hormone levels die earlier. […]
Is it possible that vitamin D is more helpful when taken with some calcium preparations than with others?
Yes. It all depends on the solubility of the product in question. It must be soluble and iodized. Otherwise it just goes through the gut. According to some figure, it is more soluble than others, even calcitonin-five to ten times more soluble. Solubility is very easy to measure by electrical conductivity. Soluble ions conduct electrical current. AAACa is amazingly soluble.*
What is the effect of exercise on [bone loss]?
Exercise will activate the bone cells to prevent calcium loss from bone. And if you stop exercise, the reverse process occurs. You lose bone. So by exercising, you are preventing bone loss. Both exercise and calcium intake are important-we can’t substitute exercise for calcium. But if Both exercise and calcium intake are important-we can’t substitute exercise for calcium. But if we exercise more, we also stimulate calcium absorption. It increases appetite, so you can eat more. and an elevated metabolism stimulates calcium absorption. So all these things aid calcium absorption.
Is weight-bearing exercise more useful?
Yes. It is physical pressure on bone that stimulates bone cells. But all exercise, weight-bearing or not, stimulates calcium absorption. Swimming, for example, is non weight-bearing. Walking is weight-bearing. Calcium absorption is also affected by emotional factors. Exercise is good relaxation that makes you feel happier and stronger. This is important because you have to be happy. You have to be out of distress to absorb enough calcium. Stress and unhappiness decrease calcium absorption. Adrenaline and cortico-steroid hormones are secreted during stress. They facilitate calcium loss and prevent gut absorption. You can eat a lot of calcium, but if it’s taken in a state of harmony, while chatting with friends, for example, then more calcium is absorbed. So what we need are three things: calcium, exercise and happiness. And of course calcium makes you happy. So calcium is everything!
What about dietary sources of calcium?
Milk is a very common source of calcium, but it also contains a lot of phosphorus, which combines with calcium and prevents it from being absorbed. Tofu is good, but not many North Americans eat it. You can eat small fish with bones, like sardines-even canned sardines. But bone calcium is also rich in phosphorus. The ideal dietary source should be low in phosphorus and high in calcium. For Americans milk is alright. It is readily absorbed. They say that broccoli and kale are better than milk, but they don’t contain much calcium and you have to eat such large quantities that it’s not practical. In general, milk is alright. If you are high in cholesterol then low-fat milk is all right. But I would recommend AAACa over any dietary source, because it has no phosphorus. It’s superior to any calcium found in foods.*
What about people who are not suffering from serious [bone loss] but just want to prevent it. We don’t want to tell everybody to go on calcium therapy…or do we?
Oh sure-everybody should take calcium. I’m not osteoporotic, but I take it regularly. As a result my EKG went down. Another thing-calcium makes you happy. It works against stress. […] Calcium has a tranquilizing effect. So kids watching television should take calcium first. It keeps you happy and peaceful. That’s why everybody needs calcium […].
So perhaps we could use calcium to promote world peace.
Well, it’s strange. You may find me overenthusiastic about calcium, but as the years go by I have no reason to reverse myself, because I don’t find anything against it. All the facts go along with my theory.
The only thing against it is constipation?
Not against it, but we expect it. America has a stressful society like Japan and we you calcium to make you less stressful, so there will be less crime and less juvenile delinquency and all these things. You need calcium in the schools.
What is the physiological basis for happiness?
Any minor decrease in blood ionized calcium will make you unhappy. The brain or muscles become excited when there’s even a slight fall in blood calcium levels, especially ionized calcium. There are two types of calcium-protein-bound and ionized. Although we’re talking about ionized calcium, we just say calcium. If there is a slight decrease in calcium then you are more excited and irritable. A readily absorbable calcium will correct the slight decrease of blood calcium promptly. A slight decrease of blood calcium makes everybody uneasy and irritable. […]
As opposed to protein-bound?
Yes, because calcium is associated with protein very easily, according to stress or other conditions. The ionized fraction act directly on the brain, and protein acts as a kind of buffer. Usually, we measure total calcium, which doesn’t change very easily, but if we measure ionized calcium we can show these effects. Calcium is a kind of hormone, in the same way as vitamin D. Simple minerals like potassium, sodium and all other salts don’t have receptors. Receptors are very important. Receptionists in offices who screen everybody coming in are like hormonal receptors. Calcium has a receptor, too. No other mineral have receptors. We call it a calcium sensor, or calcium receptor. It is a treatment for VIPs. Not like ordinary minerals. Some people may think calcium’s dangerous because we call it a hormone, but that’s not the case. We think of it as like a hormone-as important as a hormone, as specific as hormones to accomplish certain functions. So calcium is very special.
Does it fit definition of a hormone or are you using this as an analogy?
All hormones have receptors. Calcium is the only mineral with receptors. So we can say that calcium is a unique mineral that is like a hormone. Let’s call it the happy hormone!
Adequate calcium with vitamin D as part of a healthful diet throughout life, along with physical activity, may reduce the risk of osteoporosis in later life.
