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Pantothenic Acid in the Treatment of Obesity
"A Medical Hypothesis"

by Lit-Hung Leung, M.D.



This article originally appeared in the scientifically prestigious Journal of Orthromolecular Medicine Vol. 12 Number 2, 1997. The version below is from a reprint of the original article.

Pantothenic Acid and Weight Reduction

With pantothenic acid so closely related to lipid metabolism, the question is raised if it has anything to do with obesity, and hence weight reduction. In the rest of this article, we will explore the problem of weight reduction which is an equally, if not more mysterious problem than acne vulgaris.

Regarding negative calorie balance and dieting, the only guiding principle behind weight reduction is that the calorie intake must be less than the calorie output, so that there is a negative calorie balance. The body will try to make up for this negative balance by burning the fat that is stored in the fat cells, the so-called depot fat. In this process, fat in the body is consumed, and the individual loses weight. This sounds rather simple and the goal should therefore easily be achieved. In practice, however, this is quite a different story. By taking in less than what is actually needed, the dieter in fact faces two hurdles that may prove too difficult to overcome. There is the problem of hunger. It takes enormous self-restraint and determination to keep the appetite in check and when hungry there is the constant temptation to satiate this primitive instinct by grabbing whatever is available. To keep this situation in check is difficult, but not insurmountable with a conscious effort, conviction and perseverance. But more troublesome and difficult to manage is the weakness, sweating, dizziness and fainting episodes that follow the sensation of hunger. Under such circumstances, the dieter will have little choice except to start eating again, gaining back the weight that he has tried so hard to shed.

The Paradox

The key question to the whole problem of weight reduction is why is one hungry and compelled to eat when one has enough stored fat in the body? Why is one not able to convert, freely, one's storage fat into energy? Storage fat is meant as an energy reserve in times of need. Famine is a typical example of such a time. So, why can't one make use of the storage fat at a time when one needs it most? Or can one do it? This is the key question which needs to be examined very carefully.

It is not strictly true to say that the body is not able to utilize its stored fat when the situation warrants it. Not only can it burn fat stores, but it can do it with great efficiency, initially at least. The trouble is that this ability does not last. When the body is deprived of food and energy is not forthcoming from external sources, glycogen stored in the liver is first called on to furnish the energy deficit. Unfortunately, the glycogen store is very limited, and very son, even before the glycogen store is totally depleted, the body will have to mobilize its stored fat from its fat depot to supplement it energy requirement.

For a short time, the body can freely derive its energy from its stored fat. All the fat that is mobilized will be completely burnt with no wastage. But very soon, often within hours, for unknown reasons, the body can no longer maintain this rate of functioning. It can still burn its mobilized fat, but no longer as effectively and efficiently as before, with ketone bodies representing partially burnt fatty acids appearing in the blood stream and urine. With time, if food is still not forthcoming, the accumulation of ketone bodies will significantly increase, an indication that the power to metabolize stored fat is further being eroded. The individual begins to feel hungry, with the concomitant symptoms of weakness, dizziness and sweating emerging.

It has been recognized that the time taken from the start of fasting to the onset of ketosis varies, sometimes to a considerable extent among different individuals. While some may become weak within a matter of hours, others can get on very well without food for more than one to two days. In laboratory animals, it is not uncommon for some to stay active and yet free of ketosis for two to five days after the onset of fasting.

Ketosis and the Loss of Energy

Here, two most important points are raised. Why is it that some people can tolerate fasting better than the others in the sense that they can go on with their activity without ketosis for a much longer period of time? And, more important, why is the body, with the development of ketosis, losing precious stored energy at a time when the body needs it most? It appears that the body, resisting the onslaught of fasting, has installed a mechanism whereby fat can readily be converted into energy. But this mechanism is far from perfect, and fails to stay engaged for very long in some individuals, although in others the mechanism can maintain its function for several days. Still, the mechanism gets blunted with time, and is unable to efficiently burn off all the mobilized fat and provide the body with energy, with no ketogenic wasting of stored energy. This eventual blunting of the metabolic mechanism applies to every individual, without exception. In time, if fasting is prolonged, this mechanism will become even more inefficient and more ketone bodies will build up as the body loses more of its precious stored energy through the urine and the breath.

There is little doubt that the body is empowered with a mechanism to metabolize mobilized fat. The only question is why this mechanism fails to last. If one could identify the problem and prolong the mechanism of fat burning, then weight reduction would be simple. One can just fast or semi-fast the individual, and set the mechanism at work, then all the calorie deficit will be provided by energy converted from the body's stored fat. The stored fat will be steadily depleted, and the individual will gradually and slowly lose weight.

The New Hypothesis of Ketone Body Formation

It seems that the crux of the matter rests on the formation of ketone bodies. So long as the mechanism is working efficiently, no ketone bodies will emerge. What then, is the reason for the failure of the mechanism that leads to the formation of ketone bodies? There is no conclusive answer, but there are some clues. It is known that ketone bodies only appear when the body is asked to catabolize a large amount of fat, as when the energy requirement of the body is largely provided by its stored fat. At the point where the body can no longer cope with efficiently breaking down this large amount of fat, ketone bodies appear. To understand ketone body function, it seems pertinent to have a good look at the catabolism of fat and fatty acids. Briefly, fat catabolism is a process in which the stored fat in the form of triglycerides is first broken down into glycerol and long-chain fatty acids. These long-chain fatty acids are then serially broken down by a process called beta-oxidation in which the long carbon chain is fragmented into units containing two carbon atoms each. Before this can happen, the long-chain carbon has to be activated into its high-energy Coenzyme-A ester by reacting the acid with ATP and Coenzyme-A. A subsequent cleavage at the beta carbon atom of this long carbon chain by reacting with Coenzyme-A will spin off a molecule of acetyl-CoA, leaving the original long carbon chain with 2 carbons less but still as a CoA ester. The whole process is then repeated again with each process consuming one molecule of Coenzyme-A, until the whole long chain is totally broken down into many fragments of acetyl-CoA.

Take for example, palmitic acid, a 16-carbon saturated fatty acid, which is broken down by this process of beta oxidation into 8 fragments of acetyl-CoA, a total of 8 molecules of Coenzyme-A is taken up from the body's pool of Coenzyme-A molecules. All these units of acetyl-CoA will be metabolized during the citric acid cycle, releasing energy in the form of ATP, leaving carbon dioxide and water as the final end products. This is how the body gets its energy from its depot fat stores. And this is what is supposed to happen in an ideal situation, when all the mobilized fat is metabolized completely, with no wastage of energy. For very obscure reasons, when fat is broken down in large quantities, as in fasting, not all the units of acetyl-CoA will go into the citric acid cycle. Some of these units will choose to combine with each other. In the process, the molecules of acetyl-CoA will yield one molecule of acetoacetyl-CoA and one molecule of Coenzyme-A. Acetoacetyl-CoA molecule is very unstable and will rapidly decompose itself into one molecule of acetoacetic acid and another molecule of Coenzyme-A. Then, through a process of decarboxylation - an irreversible process - acetoacetic acid is turned into acetone, better known as a ketone body. The accumulation of any significant amount of ketone bodies in the body results in a certain degree of acidosis. To offset such acidosis, the body will try to eliminate the ketone bodies in the urine as well as in the breath. This is effectively a wastage of precious stored energy that is originally intended for emergency use.

Coenzyme-A Deficiency

It is baffling that two molecules of acetyl-CoA should start combining with each other to form acetoacetyl-CoA, part of which is ultimately lost to the exterior in the form of ketone bodies at a time of crisis. In an effort to understand the process, it is useful to remember the situation in the fasting state. In a bid to provide sufficient energy, the body is scrambling to produce a large amount of long chain fatty acids from its fat depot that will meet the calorie requirement. These long chain fatty acids are then broken down, all at the same time, into units of acetyl-CoA. The body sees it proper to do it this way because only by so doing, can it be in a position to provide itself with enough energy by burning these units of acetyl-CoA through the citric acid cycle. But, for every 2-carbon unit, it is necessary to attach one molecule of Coenzyme-A to it. Here, one must ask the all important and very practical question: Has the body, in its total pool of Coenzyme-A, enough of such molecules to handle this?

The body may be able to do this for a short period of time, but with an increasing portion of the body's energy needs provided for by fat, the call of extra Coenzyme-A will sharply increase. The point will be reached at which the body will no longer be able to cope with the demand, and under these conditions the body will, within its scope of capability, try to generate more Coenzyme-A to deal with the situation. The easiest way to do it is for 2 molecules of acetyl-CoA to condense to form a molecule of acetoacetyl-CoA, generating one molecule of Coenzyme-A along the way. This, in fact, also obeys the physical law of concentration in a chemical reaction. When the concentration of acetyl-CoA gets so high, the direction of the reaction will be driven towards the formation of acetoacetyl-CoA and a molecule of Coenzyme-A. To provide the body with more Coenzyme-A, which the body urgently needs in this state, the acetoacetyl-CoA molecule is quickly transformed into acetoacetic acid, generating another molecule of Coenzyme-A in the process. This is perhaps nature's way of handling a dire situation in which generating energy to sustain life is of overriding importance. This serial event, the author suspects, is the basis for the generation of ketone bodies. The subsequent event, which is the loss of ketone bodies through their excretion from the kidneys and lungs, is a desperate attempt of the body to counter the acidosis following the build up of ketone bodies, as well as an attempt to maintain a relatively normal pH of the body fluid. To maintain life, therefore, the body has no choice but to compromise by sacrificing some of its precious energy stores.

Overcoming Coenzyme-A Deficiency with Pantothenic Acid

If this postulation is true, it would mean that, by providing the body with a high concentration of Coenzyme-A, the acetyl-CoA molecules, instead of condensing with each other to form acetoacetyl-CoA, will stay as they are. They will all eventually go into the citric acid cycle and be completely metabolized. The way to provide the body with a high concentration of Coenzyme-A is rather simple. As explained earlier, the only one component of Coenzyme-A that is an essential dietary factor is pantothenic acid. If the body is provided with a large amount of pantothenic acid Coenzyme-A will be formed. To ensure that the concentration of Coenzyme-A is sufficiently high, a very large dose of pantothenic acid can be administered.

The New Concept of Weight Reduction

This is the author's concept of a new way to achieve weight reduction. A way in which a person can overcome the tricky and difficult part of weight reduction - to rid the dieter of the sensation of hunger and at the same time allow them to have sufficient energy to see them through their daily activities. This is done with a diet that is low in calories, deliberately creating a situation in which there is an energy deficit. To make up for this, pantothenic acid is administered so that any mobilized fatty acids can be converted to fully utilized energy.

A clinical study was carried out in 100 individuals of Chinese descent, 40 males and 60 females. The age range was 15 to 55 with even distribution. The participants were given a carefully designed diet containing about 1,000 calories a day, together with all the essential nutrients, to go along with this diet. 10 grams of pantothenic acid a day, in four divided doses with each dose taken four hours apart, were administered. In practice, there are alternative ways of doing it. The idea is to give pantothenic acid in between meals and when symptoms of hunger arise. The dieters had varied goals which range from losing less than 5 kg to more than 30 kg. Approximately half of them aimed at shedding 10 to 20 kg. The average weight loss was about 1.2 kg per week. Ketone bodies in urine were monitored and were found absent in most instances. Occasionally, small amounts were present, indicating that in some individuals, an amount of pantothenic acid larger than 10 grams was required. The patients exhibited no weakness. Often, there was the desire to eat, but no actual hunger. Daily activities could be carried out normally. With determination and perseverance, this process can be continued day after day, week after week, until the desired weight is achieved. The rate of weight loss can be regulated if the calorie deficit is made larger by eating very little, or it can be slowed down by eating more, keeping the calorie deficit to a very low level. However, it is never a good idea to lose weight too quickly.

The Salient Features

In choosing to reduce body weight with this method, there are three salient features to be noted. One is the unusually high success rate, which is understandable. To ensure success, the only prerequisite here is to maintain a calorie deficit through dieting. There is no hunger to worry about, and weakness will not be a problem. With these two hurdles removed, extended dieting should not present a major problem. The other feature, of course, is the significance of exercise, which is the mainstay of most conventional methods for weight reduction. What is necessary is the presence of a large amount of pantothenic acid in a semi-fasting state, so that stored fat will be burnt slowly and steadily. If the dieter does exercise, it certainly will help to hasten the process.

The third feature, of course, is the absence of side effects with such therapy. This is quite unlike the conventional drug therapy with stimulants and appetite suppressants in which unpleasant side effects are common. Pantothenic acid, being a food, is non-toxic. No toxicity has been observed by the author with anyone taking pantothenic acid in doses of 10-20 or more grams a day over prolonged periods, in some cases of more than a year.

Not only is there no toxicity, there is actually improvement of the general state of health for those taking large amounts of pantothenic acid every day. This too is not difficult to understand since pantothenic acid plays so many important and diversified roles in the body as a coenzyme. Any supplement which will help the body to accomplish important reactions that it previously was unable to carry out, is evidence of a prior deficiency state. Such reactions are important to the optimal health state as well as the general well-being of the individual. When a relative deficiency state is rectified, many of these important reactions can go on, helping to improve the general well being of the individual.

Pantothenic Acid and Weight Reduction

It seems that aside from its other functions, pantothenic acid is important in keeping a stable body weight. An individual has to have enough of it to stay away from getting overweight if there is a deficiency, just missing a meal may bring on a certain degree of ketosis, reflecting clinically as hunger, weakness, and perhaps giddiness. All these are signals that urge the individual to have food immediately. This will make any attempt to reduce body weight not only very difficult, but almost impossible. It is not that the dieter is lacking in will power, but rather in pantothenic acid, and it is unfair to label him as somebody who lacks perseverance and motivation. He does not really have a choice under such circumstances other than to eat.

And it is in these people that whenever they overeat, all the extra energy deriving from that meal will be put safely away in the fat depot. It seems that this primitive instinct for storing food away in the fat cells for the future is retained, despite a deficiency in pantothenic acid. This leaves the group of people, who already have difficulty in reducing their body weight, particularly prone to put on weight. What a Herculean task it must be for those people without enough pantothenic acid in their bodies to achieve weight reduction! Failure to supplement dieters with pantothenic acid is perhaps the main reason for the very high failure rate of diets which use conventional methods.

Further Supporting Evidence

With the same principle, it is possible to explain many of the commonly observed phenomena that occur around us. For example, it can be explained why females have a higher fat ratio in their bodies and that they are more prone to gain weight than their male counterparts when they reach middle age. It is not the direct role of female hormones, as conventional wisdom postulates. One has to remember that the monthly menstrual cycle, which requires plenty of pantothenic acid to support the cycle, is continually drawing on the pantothenic acid pool that is very often deficient from the start. This makes pantothenic acid deficiency particularly common in the females, especially at a time around their mid-30s. This is the time when the cumulative effects of 20 years or so of reproductive cycles, with each cycle soaking up some pantothenic acid from the body's total pool, begins to take shape. Added on to this is pregnancy. This requires even more female hormones to see it through, allowing the deficiency to go even more severe. With each pregnancy the situation goes from bad to worse. That is why, even though some women with one or two children may still be able to retain their slim figure with a carefully watched diet, many more gain a significant amount of weight. For those with many children, few women can manage to stay slim, no matter how rigorous their dieting attempt may be. Their pantothenic pool is dwindling.

There are probably reasons for obesity other than a deficiency in pantothenic acid alone, the most obvious of which is overeating. But judging from what has just been described, it appears that pantothenic acid must play a significant role in obesity as well as weight loss. The body has a natural tendency to store away any excess calorie intake in its fat depot. Pantothenic acid is the key that unlocks this fat depot and is the agent that converts the mobilized fat into energy. With plenty of pantothenic acid in the body, this conversion is always simple and easy, allowing the body to retrieve as much energy from its depot as is necessary. On a low calorie diet, the amount of pantothenic acid that is required to keep ketone bodies at a minimum level can actually be titrated with the calorie intake. The lower the calorie intake, the larger an amount of pantothenic acid is necessary. Within a certain range, the amount of pantothenic acid required forms almost a linear relationship with the calorie intake, which makes the larger amount of pantothenic acid necessary. To maintain one's body weight after one's goal is reached it is necessary to supply the body with 2-3 grams of pantothenic acid each day to enable the body to freely convert mobilized fat into energy so the individual will remain active, agile, and full of energy.

The More Important Message

The relationship of pantothenic acid with acne vulgaris and weight reduction is important and carries a message that is of greater significance regarding the use of megadoses of vitamins. The war of words between the Linus Pauling camp and the mainstream medical profession serves to illustrate the opposing views of the two sides. This debate went on for more than two decades, with the mainstream medical profession maintaining their view that vitamins in large doses are not necessary and until further proof is forthcoming, the idea of magadosing is quite wrong. It is believed that this proof is now available, though not coming from ascorbic acid, but from another vitamin - pantothenic acid.

This conclusion leaves us pondering another important corollary: What is the position of vitamins other than pantothenic acid and ascorbic acid? Does one need huge doses of these vitamins as well? There are already hundreds of papers on vitamin C over the last 20 years that provide evidence that large doses of the vitamin do help in various clinical conditions. With pantothenic acid, the situation is probably very much the same. Already, there is evidence that those who take large doses of pantothenic acid, either for acne vulgaris or for weight reduction, feel a lot better, and do not tire as easily. Their skin remains supple and taut, even after losing more than 20-30 kg of body weight. This is quite unlike other methods of weight reduction in which excess looseness of skin normally follows any significant weight reduction. In the future, other diverse conditions, including conditions that are not very well defined clinically, may be helped with large doses of pantothenic acid as will likely be true with most other vitamins and nutrients.

Conclusion

I would like to conclude this paper with another question: Why is it that vitamins are needed in such a large dosage? Are they not supposed to work as catalysts which can be recycled? To assume that coenzymes work in the way that textbooks portray them - as a catalyst that will not perish - is perhaps unrealistic. Not only are they perishable, but the substrates in the citric acid cycle, or for that matter, probably any substrate in biochemical cycles in the body, may share the same fate. The following observation helps to illustrate this. In the course of weight reduction, a few dieters chose to hasten their progress. They ate very little, sometimes nothing at all for more than two days, surviving only on water and a huge dose of pantothenic acid. Theoretically, these people have more than enough of fat stored in their body to see them through for many days if not weeks. Since they have so much pantothenic acid in their body, they should be able to generate enough energy without experiencing ketosis. But this is not the case. Usually, in less than 2-3 days, they too develop ketosis regardless of how much pantothenic acid is given. Under such circumstances, the body's many acetyl-CoA units cannot go into the citric acid cycles to be burnt - not because of a lack in pantothenic acid, but a lack in the substrates. This is evidenced by the fact that the situation can readily be reversed by giving the dieters a small amount of carbohydrates. Therefore we see how substrates of a biochemical cycle can be worn out, and need to be replaced constantly. The same probably applies to other coenzymes of the body.

Although this observation does not fully answer the question as to why large doses of vitamins are needed, it does throw some new light on the previous concepts about vitamins and coenzymes. With the present clinical results of pantothenic acid on acne vulgaris and weight reduction, it is perhaps time to focus more attention on how high doses of vitamins and nutrients can be used in the prevention and treatment of diseases.


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