In response to your request for information regarding the growth and nutrition of hair, particularly scalp hair of humans, I have done extensive research on the matter and wish to give you the following report:

I. Growth and Development of Hair

According to Myers and Hamilton (1) a follicle of the human scalp produces approximately .35 millimeters of hair shaft per day. Regardless of its size, only a small mass of cells at the base of the follicle, the matrix, produces this germinative tissue, and for the synthesis of complex proteins farther up in the follicle, to produce this much hair is of a magnitude greater than is found in most tissues (2). Within each follicle, mitotic activity of the cells of the matrix and synthesis of protein go on unceasingly as long as the hair is growing; growth, however, is periodically abruptly arrested and generation of a hair ceases. At this time there is a destruction of the major portion of the hair root and what cells remain enter a period of absolute quiescence. After a variable interval of time, the dormant follicle bursts into activity. A period of organogenesis follows during which an entirely new hair root is regenerated and the production of a hair is resumed. The cycles of growth of each follicle consist of the building up and tearing down of the structure. After a period of rest the follicle is built anew from raw materials and each hair follicle goes through the identical processes. It is important to point out at this point that many of the metabolic requirements of the cells of the hair follicle must be met at this time or adequate and optimal hair growth will not occur. This means that certain vitamins and minerals must be present in adequate proportions or there will be faulty or nonexistent hair growth.

Abundant ribonucleic acid (RNA) is characteristic of those cells of the hair follicle that carry out appreciable protein synthesis. Deoxyribonucleic acid (DNA) is found only in the nucleus of the hair follicle cell. Like that of RNA, the content of DNA increases in cells during division. An increase in DNA content appears to be indirectly related to an increase in protein synthesis (3).

For this reason, those nutritional factors such as folic acid and B12 which are vital for synthesis of some of the building blocks of nucleic acid must be included in and formula for hair growth. These will be covered later in this report.

Flesch (7) has reviewed the effect of diet on hair growth and states that impaired growth or loss of hair is a common and early nonspecific response to many nutritional deficiencies in animals. Van Koetsveld (8) has reviewed work on the influence of feeding on the coats of animals.

In actively growing cells of the hair follicle, the glycogen content has been shown to be greatly increased (4&5). Very little of the glycogen is present in resting follicles and Montagna (6) assumes that the glycogen in the outer root sheath of the follicle is the source of the energy for protein synthesis during hair growth. For this reason, enzymes related to glucose metabolism and glycogen build-up are very important in hair growth and those minerals and vitamins used by the body as cofactors must be present in adequate amounts.

II. Aging of the Human Scalp

Montagna and Ellis (9) have done studies of the capillaries surrounding the hair follicles and have called attention to some of the striking changes that occur during the aging process in the human scalp. These observations have led to a comprehensive survey of the human male scalp from birth to senescence, and it will be shown that remarkable changes do occur in the cutaneous structure of the scalp and their accompanying blood vessels.

Certain aging changes in the human male scalp such as a receding hairline, the gradual thinning and graying of the hair, and, frequently, the partial or complete balding are quite apparent. These are changes that involve the hair follicle and are the result of interactions between the sex hormones of the male and the genetic constitution of the individual (10). In Montagna and Ellis' book (see reference 2, page 474) they adequately demonstrate the fact that in an older person the total number of the capillary loops supplying the hair follicles is considerably diminished. This diminution of blood supplied to the hair follicle would of necessity require either greater blood flow through these follicles or an increased amount of nutrients of various types such as vitamins, minerals and amino acids in order to supple the hair follicle with the same amount of these materials. Since the former is unlikely, it appears that the latter course, mainly supplying more nutrients, would be the most logical way to keep the hair follicle in its presenescent state.

Bullough (12) has shown that mitotic activity in the epidermis is dependent upon an adequate supply of glucose and oxygen. The scant subepidermal circulation in the aged scalp cannot provide a very rich supply of nutrients to the epidermis. The loss of rete pegs results in a considerable decrease in surface area at the dermal-epidermal junction, and this might be considered to be a compensatory factor.

The causes of the circulatory changes are not known. There is a distinct correlation between the presence of hair in the scalp and the integrity of the subepidermal plexus of blood vessels. Even the scalps of very old subjects have remnants of the subepidermal plexus around growing hair follicles.

I will now attempt to numerate some of the nutritional factors that should be present in any preparation designed to assist nutritionally with the growth and health of hair. I will begin with certain minerals which I feel are very important and progress from there to certain of the B-complex and other vitamins.

III. Zinc

It has been known for many years that in animals when there is zinc deficiency, the hair follicles will atrophy (13&14). It has also been noted that there is a marked impairment of DNA and protein synthesis in experimental animals whenever zinc deficiency is present (15&16). And in fact, without DNA replication, growth and protein synthesis are severely limited (17&18). Studies by Altmann (19), Shin (20) and Tal (21) have shown that zinc influences the confirmation of nucleic acids. As previously mentioned, without the proper formation of nucleic acids, the cell replication and hence hair growth cannot occur normally.

It has been shown in many species (22) that coarse and sparse growth of hair generally accompanies zinc deficiency. Duncan's textbook of diseases of metabolism (23) also points out the vital role which zinc plays not only in protein synthesis but in certain enzymes including carbonic anhydrase, malic dehydrogenase as well as lactic anglutamic dehydrogenasis. Malic dehydrogenase is very active in the Krebs cycle and lactic dehydrogenase is associated intimately with the glycolytic cycle. These enzymes are reviewed extensively in Duncan.

For all the above reason related to its action and enzyme chemistry and protein synthesis, I recommend zinc as being a primary or being the primary mineral present in your formula. I would recommend, however, that when possible you utilize zinc gluconate or orotate as a more easily absorbed salt than zinc sulfate. I have found through experience that zinc sulfate occasionally will cause some gastrointestinal distress whereas I have never seen it with the gluconate or the orotate salt of zinc.

IV. Copper

Copper deficiencies in experimental animals have reduced the pigmentation of hair (24, 25, 26 & 27).

According to Duncan (23), when human copper deficiency is observed it is the result of limited intake, inhibition of absorption or excessive loss of the metal. The importance of copper in hair metabolism is pointed out quite well by Fell (29) in his study of copper content of human tissues and body fluids. Fell points out that only two of the tissues in the body contain more copper than hair, mainly liver and brain tissue. Beinert (28) has shown that copper is present in the enzyme cytochrome oxidase, along with iron.  This particular enzyme is very important in hydrogen transport mechanisms of respiration of the hair follicle cell.

Another very important enzyme present in hair follicle cells is tyrosinase, present principally in the melanosomes of the skin and eye. This is an enzyme which catalyzes a series of reactions resulting in the conversion of tyrosine to melanin. This melanin is very important in certain types of hair color. Absence of tyrosinase or of its function results in albinism (30). You can see the importance, therefore, of copper in the metabolism of the hair follicle.

Another important function of copper has been shown in experiments by Sieve (31). The graying of hair has been produced experimentally by this investigator by a lack of copper along with folic acid, pantothenic acid and PABA. While this particular experiment did not demonstrate that deficiency of copper alone caused graying, it certainly was suggested that copper deficiency plays an important factor in some cases of graying of the hair.

In the synthesis of hair protein, the formation of disulfide bonds is very important for the integrity and structure of the hair itself. Copper has been shown to play an important catalytic role in the formation of these disulfide bonds (32&33). One demonstration of this or the effects of this defect of copper deficiency can be found in Menke's kinky hair syndrome which was described by Danks (34). In this particular defect there is a marked change in the texture of the hair caused by copper deficiency which can be corrected by the adequate addition of copper to the patient.

The basic defect found in the hair is an abnormality of the hair shaft structure and increased virility of the hair. The serum copper is decreased and the hair sulphydryl-disulfide ratio is increased. The hairs appear similar to those found in the wool of copper deficient sheep and the defect appears to be associated in these patients with a defect in intestinal absorption of copper. It is postulated by Danks that copper deficiencies in general might produce a similar problem.

Another hair pigment which is found in humans is called pheomelanin which appears to produce the yellow red pigment found in hair. According to Flesch and Rothman (35) and Russell (36), this is also a tyrosinase dependent pigment and requires copper for its action and its formation. It is postulated that lack of adequate copper for an enzyme cofactor would produce defective pigment formation in patients with yellow or red or combined coloring. Mason also points out that zinc is required in addition to copper for part of the chain of chemical reactions triggered by enzymes that finally produces melanin or its derivatives.

V. Manganese and Iron

I will cover manganese and iron together in the same section since some of the enzyme reactions and some of the biochemical pathways in which they are active are the same. Wacker (39) discusses nucleic acids and metals in his paper. It was found that chromium, manganese, nickel, iron and other metals were present in RNA from diverse biological sources, pointing out the importance of manganese and iron in the synthesis of RNA. Prasad (40&41) points out that manganese and iron are important in the Kreb cycle. Without the presence of adequate amounts of these two metals, the Kreb cycle of oxidative energy production cannot occur at optimal levels. Isocitric dehydrogenase (IDH) which is a manganese dependent enzyme and succinic dehydrogenase (SDH) which is an iron dependent enzyme are two important links in the chain of the Kreb cycle. Without optimal function of the Kreb cycle, adequate high energy phosphate bonds cannot be produced and therefore adequate glycogen which is vital for follicle growth cannot be built up to be used as energy at a later date. Histochemical studies of the hair follicle by Montagna (42) have shown how easily iron can be localized in the hair follicle and how important it is, both in the oxidative and hydrogen transport systems of the hair follicle. Incidentally, hydrogen transport is the usual method by which cells oxidize materials. Instead of direct addition of oxygen, hydrogen is removed which accomplishes the same thing, mainly oxidation of a compound.

Another study by Cunningham (43) showed that iron deficiency could cause hairlessness in rats.

VI. Iodine

Iodine intake of many persons has been shown to be markedly deficient according to a study by Saxena (44).

Organic iodine such as found in kelp is better retained (45) and less readily lost in the urine than potassium iodide (46).

In thyroid deficiency caused by low iodine intake in certain experimental animals, there was loss of hair as noted by Cuthbertson (47). This indicated the importance of an adequate supply of iodine and its formation into thyroxine for hair growth to proceed normally and at optimal levels.

Thyroxine then stimulates a spontaneous replacement of hair in intact and thyroid hormone deficient animals (2, page 369). The cycle of growth remains normal regardless of how activity is initiated in the follicle. The mechanism of thyroid action on hair growth is not known, but it is believed that this may enhance the utilization of essential nutrients by the follicle (48). Perhaps thyroxine stimulates the skin and hair follicles directly and acts at the mydocondrial level of organization on exidited enzyme systems.

VII. Folic Acid and B12

An adequate supply of nucleic acids for formation of nucleo-proteins must be present at the hair follicle site for adequate and healthy hair growth to occur. both folic acid and vitamin B12 appear to be separately concerned with production of nucleic acids (50). Some believe that vitamin B12 is concerned with the synthesis of uracil, one of the building blocks of RNS and that folic acid converts uracil to thiamine, which is found in the RNA as a very necessary component (51).

It has been noted that persons made deficient in folic acid often become completely bald, but the hair grows in normally after the vitamin is given (52). reference is made to the article by Sieve (31) in which lack of folic acid is one of the components which cause graying of hair with restoration to its natural color when replacement therapy was given.

A folic acid deficiency prevents dozens of important physiological functions: interferes with the utilization of sugar and amino acids, stops all cell division and healing, and causes the hair, eyebrows and eyelashes to fall out (53,54&55). Almost all of these functions are related to adequate and healthy hair growth.

The folic acid / tetrafolic acid system provides a unique mechanism for the reduction of carbon to methyl that can be transferred to a methyl acceptor. This is the explanation of the synthesis of choline, creatine and other methyl containing metabolites in animals fed diets deficient in sources of preformed methyl. Thus the folic acid / tetrafolic acid system is a vital part of the metabolism of man and is very important in the synthesis of hair follicle proteins and structural compounds. The folic acid / tetrafolic acid system by reversed reactions also provides a mechanism for the addition of partially oxidized carbon during the synthesis of serinen to such structures as the purine and pyrimidine rings (ref 56, page 47).

Duncan (23) has described folic acid deficiency as possibly the most common vitamin deficiency in North America today. Its prevalence seems to be on the increase and responsibility for this at least in part rests on the exclusion of folic acid from many diets in this country today. Many physicians hesitate to give folic acid and many patients hesitate to take folic acid because of the fear that it might correct the anemia of certain B12 deficiencies while allowing neurological manifestations to progress.

According to Duncan there may be many reasons for the deficiency of folate including dietary lack, impaired absorption, increased requirements, antagonism from drugs prescribed for patients and lack of protection of folate coenzymes that is related to either vitamin C or iron deficiency.

Studies show that vitamin B12 is closely related in function to four of the important amino acids or forms of protein, folic acid, and pantothenic acid. Thus without vitamin B12, the function of the nutritional elements may not be optimal (57). Duncan (23) has also pointed out the function of vitamin B12 in immediate reduction and isomerization reactions. It is intimately related metabolically with folic acid. In this regard, vitamin B12 can alter the reduction level of the single carbon units transferred by folic acid coenzymes.

It participates in the reduction of ribos to deoxy ribos, converting uracil ribotide to uracil deoxyribotide prior to the addition of a single carbon unit by folic acid coenzyme to form thiamine deoxyribotide. In addition, vitamin B12 is an accessory to folic acid in some transmethylation reactions and may be necessary for the activity of folic acid conjugases. The conversion of methyl malonyl CoA to succinyl CoA requires vitamin B12, and in the deficiency state, large amounts of methyl malonylate are excreted in the urine.

For all the reasons cited above and to somewhat repeat myself, it is important for any actively growing tissues such as the hair follicle to have adequate supplies of folic acid and vitamin B12 present daily for optimal hair growth and for healthy hair growth to occur. Therefore, i strongly agree with the addition of these most important elements to your vitamin formula, Head Start.

VIII. Choline and Inositol

Choline and inositol are also very important for the metabolism of hair both in a direct and indirect manner. It has been noted that thyroxine cannot be made without choline (58) and that rats become hairless if kept on diets low in inositol (59). Inositol was mentioned in the Science Newsletter (60) in 1956. It was stated there that inositol was needed for growth and survival of cells and bone marrow, eye membranes, embryos, gut and other rapidly growing tissues like hair follicles. Inositol has been known to appear in human hair with speculation as to its value in restoring color to gray hair. In the book "Inositol" (61) published by Corn Products Sales Company, Many observed physiological values of inositol are listed.

Choline is important in methylation reactions that result in the formation of thiamines and thymydylic acids from uracil and deoxyuridilic, respectively. Of great importance is the occurrence of additional methylation reactions that are believed to occur after nucleatides are built into polymeric, macro molecular nucleic acids (62).

Changes in hair pigment were produced by omission of choline or pantothenic acid from the diet (63) and Wooley (64) showed the relationship of choline and inositol to growth of hair in animal experiments.

Engle (65) found inositol to be an essential growth factor for normal cells including hair follicle cells. And Wooley (66) showed that spontaneous cure of alopecia in animals was dependent on an adequate supply of inositol. In light of the apparently essential role that choline and inositol play in the growth and proper nutrition of hair cells, it would be certainly logical to include both of these important compounds in any formula supplying the needs of the hair.

IX. Calcium Pantothenate

Pantothenic acid and its calcium salt, calcium pantothenate are also quite important in hair growth and in nutrition of the actively growing hair follicle cells. As previously mentioned in a paper by Owens (63) changes in hair pigment were produced by omission of either choline or pantothenic acid from the diet. Pantothenic acid was found by Wooley (67&68) to influence alopecia in animal experiments. Flesch (7) has noted that one of the deficiencies said to cause impaired hair growth is pantothenic acid. Deficiency of pantothenic acid and riboflavin in black children not only caused depigmentation, but made their hair grow straight (69). This deficiency seems to be associated with the utilization of copper. The skin of rats deficient in pantothenic acid may contain as much as five times the amount of copper in normal skin, ie: the copper cannot be utilized and accumulates (70). One can therefore see the complex relationship of the vitamins and minerals to each other and to the proper growth of the hair follicle cells.

Pantothenic acid and inositol functions are related in that too little pantothenic acid in the diet appears to disrupt the function of inositol (57).

Rodell's book on the vitamins gives a number of references to graying of hair and paraminobenzoic acid and panthenol as well as the efficiency of unsaturated fatty acids when adequate supplies of pantothenic acid are present. It should be pointed out that where unsaturated fatty acid deficiencies are present you may find dry skin, brittle, lusterless falling hair and dandruff. Therefore, the pantothenic acid appears to have a rather protective effect on these unsaturated fatty acids. Reference is also made by an article in the British Medical Journal (71) to restoration of color to gray hair using pantothenic acid in certain experiments.

Pantothenic acid functions and is present in all living cells, mostly in the form of coenzyme A. CoA is the cofactor of one of the most important enzymes of intermediate metabolism. It is formed by joining pantothenic acid with other materials to form a structure of coenzyme A. CoA activates acetate by converting it to an acetyl CoA. The pivotal compound for many pathways. Duncan (23) states that acetyl CoA is concerned with #1 - acetylation of choline, aromatic amins and other substances detoxified by acetylation; #2 - synthesis of fatty acids, acetoacetic acid, cholesterol and styroids; and #3 - oxidation of pyruvate.

For our purposes in designing a formula which would help stimulate the metabolism of the hair follicle, the third is the most important. In the metabolism of glucose and other substances, pyruvate plays a pivotal role. In order to enter the Kreb cycle and produce energy by oxidation it is necessary to change pyruvate to acetate in order for the two carbon acetates to enter the Kreb cycle. Without adequate supplies of coenzyme A this will be impossible and the hair follicle nutrition will suffer. Therefore, it is an absolute necessity that pantothenic acid be added to this formula.

X. Paramino Benzoic Acid

In the experiment by Sieve (31) the lack of copper, folic acid, pantothenic acid and PABA influences the intestinal bacteria so that they can produce folic acid and folic acid in turn helps the body to assimilate pantothenic acid. Ansbacher (72) also seems to give corroboration to the theory of the action of PABA and pantothenic acid in protecting the natural color of the hair.

XI. Niacin

Those preceding nutrients in the B complex and niacin have been found to be very important in the nutrition of various experimental animals and the vitamin B complex taken over long periods has been found to restore human hair pigmentation (73). There was also an article by Hudgins (74) concerning the peripheral blood vessel dilating effect of niacin which would include, of course, the blood vessels of the scalp.

Frost (75) has noted that dietary deficiencies of certain vitamins can cause achromotrichia (problems with hair color). Bullough (12) has shown that there is a known dependence of epidermal mycosis on the active respiration of the epidermal cells. His experiments show that this was also similarly dependent in the follicular matrix. Energy produced through the oxidation of carbohydrates is the primary source of the energy necessary for synthesis of hair cells or of hair in the follicle. Both in the oxidation of glucose and glycogen and in the formation of glycogen from its precursors. This is doubly important in the hair follicle cell since the synthetic potential of the proliferating cells of the follicle bulb is high relative to that of other tissues (ref 2, page 307).

In summary, certain vitamins, minerals and amino-acids are crucial to the metabolic pathways involved in keratin protein metabolism. Without the nutrients cited, the hair growth process will slow or cease.

Therefore, I conclude that there is an adequate research basis to justify product effectiveness claims for a vitamin, mineral and amino-acid complex designed to supply the nutrients needed by healthy growing hair.