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Justus von Liebig was born May 12th 1803 and died April 18th 1873 in Munich. He was a famous chemist identified with the early development of Biochemistry, although he was concerned very much in the development of organic, biological and agricultural chemistry as well as making significant contributions to chemical education. Von Liebig’s scientific career blossomed at the universities of Giessen and Munich. His laboratory at Giessen became world famous and certainly established a pattern for chemical education throughout Germany. His discoveries and investigations were numerous and he founded a journal in 1832, “Annalen der Chemie”, which remains to this day one of the major chemical research periodicals.

Von Leibig noted in his investigations of the chemistry of plants and animals a frequency occurrence of the organism’s use of nutrients. He observed that nutrients were often utilised inadequately although there was an abundant supply. He discovered that there is such an interdependence between nutrients that the organism’s utilisation of the various nutrients was determined by that nutrient which was provided in the least amount.

He therefore developed what he called, The Law of the Minimum, which states:

“The development of living beings is regulated by the supply of whichever element is least bountifully provided.”

Although this law is rarely referred to in modern Biochemistry its existence is well recognised. As a principle it does not precisely conform to the above definition but the variants are similar. This negative feedback mechanism is employed widely in the living organism. It is a major feature of biological control. Negative feedback refers to the extremely fine control of the activities of enzyme molecules as they influence various events in a chain reaction. The complex synthesis of various components within the cell frequently involves a succession of biochemical reactions with the production of intermediates – the bi-products of intermediary metabolism, which then feedback and influence the whole chain of chemical events.

As an example, the formation of purines that are incorporated into nucleotides begins with common metabolites that are used for many purposes. Each step in the series of chemical events in the formation of the nucleotide requires an enzyme. The organism’s fundamental problem is how to regulate the rate of a long sequence of biochemical reactions in order to produce enough purine nucleotides but not too many, and also without accumulating too much otherwise useless intermediaries. This problem is solved not by regulating each separate reaction in a long sequence but by making the ultimate products of the sequence, the nucleotides themselves, inhibitors of the first reaction in the purine synthesis.

The body’s use of iron is to some extent regulated by the presence of copper. An early symptom of copper deficiency is anaemia. Two minerals, and I use that word conventionally for it is more correct to say organised minerals, are calcium and phosphorus. Their relationship in biochemistry is paramount and scores of papers have been written on this subject, textbooks also, a good one being by Henry C. Sherman entitled, “Calcium and Phosphorus”.

The use of calcium in bones and teeth cannot be utilised adequately without the presence of adequate phosphorus. Of course these two elements, calcium and phosphorus, are so widely distributed among natural foods that it is unlikely that we may have a problem with them, although at the present time a great deal is being espoused about osteoporosis which again has little to do with calcium and maybe considered as a variation on The Law of the Miniumum. The more protein we consume the more urea we excrete, the more calcium we lose from the kidneys. Whilst this is not a direct interpretation of the Law of the Minimum it is certainly a variation of the principle.

A further example is the protein sparing influence of carbohydrates. In all natural foods there is a wide variety of nutrients. They are absorbed more or less simultaneously and the presence of each influences the use of the others. When protein is absorbed from the gut, when a fairly pure protein food is eaten, what is called oxydative deamination takes place in the liver. Through this mechanism some of the protein is lost. However, if carbohydrate is taken with the protein as occurs in natural vegetarian foods, the presence of the carbohydrate in the absorptive product spares the protein and it is preserved for appropriate body use. At this juncture of course the carbohydrate has been reduced to simple carbohydrate and the protein has been broken down to its constituent amino acids.

Another variation of this principle may be found in the interesting story of vitamin B12 (cyanocobalamin) which is the form of the compound originally isolated during the long search for vitamin B12. Most of us identify cyanide as a highly toxic substance, a dangerous poison. It is produced by many micro organisms in small amounts and its affinity with cobalamins is very strong and cyanocobalamin may be created whilst meddling with microbial cultures. Large doses of hydroxycobalamin have been employed in the treatment in cyanide poisoning. Nearly all of the cobalamin found in animal tissues is present in the adenosyl or methyl forms which are the natural dietary forms of the vitamin.

The tissues of people suffering from pernicious anaemia are deficient in vitamin B12. As the name implies, pernicious if untreated, is ultimately fatal with serious degenerative changes of the blood and central nervous system that result in abnormal sensations, motions, behaviour and thought.

Until 1926 pernicious anaemia was a fatal disease. Minot and Murphy demonstrated that treatment with large amounts of liver could reverse the symptoms and even prevent a recurrence. The cause of the disease was uncovered by Castle and his co-researchers in 1929 when they demonstrated that normal gastic juice contains an intrinsic factor that is essential for the absorption of vitamin B12. So curiously pernicious anaemia is more a defect of the stomach than a dietary deficiency disease. The absorption of the cobalamins presented in the diet depends on the formation by the gastric mucous membrane of carbohydrate rich protein known as intrinsic factor.

People who develop pernicious anaemia do not make this protein. Before the modern treatment of pernicious anaemia with injections of vitamin B12, patients consumed hog stomach preparations to provide the missing intrinsic factor and lots of liver to supply the vitamin or extrinsic factor. As has been mentioned elsewhere, the quantity of cobalamin required in the diet is exceptionally small, about one twenty-eighth million of an ounce a day, and it also appears that even those with pernicious anaemia can absorb sufficient for nutritional needs if the oral dose is raised to the level of one micromol a day.

Many vitamins function as enzymes or catalysts. Some function predominately in trains of nutritional events. A variation of the principle we are discussing is the action of anti-vitamins or vitamin antagonists. Research in the chemical structure of vitamins has lead to considerable understanding of their characteristic reactions. We know that some are destroyed by oxidation or light or inactivated by their reaction with other compounds. Any substance that interferes or prevents the absorption or metabolic action of a vitamin in the organism is referred to as an anti-vitamin or vitamin antagonist. As an example avidin is an antagonist of biotin. Sometimes substances called analogs, chemical compounds so similar in chemical structure to the vitamin that it is capable of intiating the reactions like the true vitamin but cannot complete them, thereby it blocks the space where the real vitamin could function.

An interesting and educational example of this type of reaction is a particular folic acid antagonist which has been used clinically in the treatment of cancer. The underlying theories that rapidly dividing cells such as malignant cells, may need more folic acid than normal cells; therefore if we can trick these cells into using a nutrient that it demands in large quantities by providing one that it mistakes for the nutrient, this antagonist might inhibit the growth of the abnormal cells. Unfortunately, as one might anticipate, the folic acid antagonist inhibits the growth of normal as well as abnormal cells.

Another way that nutrition may be interfered with is through the ingestion of various drugs. It is normal for bacteria in the intestinal tract to synthesise certain vitamins, especially B12. When a sulpher or an antibiotic is taken orally the intestinal bacteria may be decimated or rendered incapable of synthesizing vitamins.

Competitive inhibition is another example of this principle where nutrient and metabolites may compete with each other for a particular process. The imbalance of supply and demand may create serious problems.

A number of studies relate to vitamin D and magnesium absorption. They demonstrated the effect of vitamin D on improving the reabsorption of calcium and phosphate in the intestine and the influence of vitamin D on magnesium absorption – there is obviously a very important synergistic relationship but current research evidence is somewhat contradictory.

Iron is a widely distributed element in foods, but numerous intraluminal factors decrease absorption. They include:-rapid transit time through the gut

achylia
various malabsorption syndromes
precipitation by alkalinisation
phosphates
phytates
an ingested alkaline clays often found in antacid preparations
tea and coffee both reduce iron absorption substantially
iron 1 ` absorption may be reduced by about 60% by tea and about 40% by coffee -phytates often found in whole grains such as wheat, bran, maize, chelate iron reducing its absorption.

All of the necessary nutrients must be provided in our diet for us to be adequately nourished. It is pointless to take a few individual nutrients out of their natural context, concentrate them and consume them in pill form. This, to the hygienists, is the royal road to nutritional disaster. Whilst most of the problems are minimal and the excess of particular nutrients is merely excreted in the urine or passed out through the gut it is not the optimum or desired way by which to solve nutritional problems.