Dr. Razack

PRODUCT INFORMATION
CRINAGEN
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The new and improved Crinagen now contains 5% azelaic acid and Proanthocyanidins from grape seed extract for maximum potency. The only one of its kind topical lotion for hair loss prepared in accordance to the clinical study reported in the British Journal of Dermatology - up to 98% reduction in DHT !!
Safe for both men and women. 

The current version of Crinagen contains the following: Distilled water, Polysorbate 20, Gamma linolenic acid, Proanthocyanidins (procyanidin oligomers from grape seed extract), Azelaic acid, Zinc acetate hydrate, Niacin, Vitamin B6 (as Pyridoxal-5-phosphate), Saw palmetto extract, Ginkgo biloba, Alpha linolenic acid, Oleic acid, Linoleic acid, Arachidonic acid, Palmitoleic acid, Tea tree oil, Witch hazel extract, Epilobium augustifolium, Epilobium parviflorum, Riboflavin, Vitamin E (as d-alpha tocopherol). 

The following is a detailed discussion of some of the key ingredients in Crinagen. 

Azelaic acid (pronounced az-uh-LAY-ic) is a simple molecule ( HOOC(CH2)7COOH, CAS Number 123-99-9, also known as 1,9-Nonanedioic acid) that is found in some whole grains and in trace amounts in human bodies. Although it is an acid, it is an extremely weak acid - much weaker than vinegar. It's current use in medicine is in Azelex, which is a cream base containing azelaic acid as 20% of its weight. Azelex is available by prescription in the USA and is used in the treatment of acne. More description of its medical properties, including cautions, can be found here:
http://www.nursespdr.com/members/database/ndrhtml/azelaicacid.html

Azelaic acid may be useful as a hair growth stimulant. A research report by Stamatiadis in 1988 suggested that azelaic acid (and combinations of it and zinc ion and vitamin B6) was a strong type I 5-alpha reductase (5-AR) inhibitor. The enzyme 5-AR (both types I and II) convert testosterone to dihydrotestosterone (DHT). DHT has been shown to contribute to male prostate enlargement (benign prostatic hyperplasia, BPH) and to damage hair follicles. The abstract of that article is further down this page.

We have not seen research that directly links the use of topical azelaic acid (or azelaic acid with zinc and B6) with hair growth. We feel that there is sufficient literature backing (in the Stamatiadis study and others) to include it in a Crinagen preparation.

Some people have obtained Skinoren azelaic acid cream (which is 20% azelaic acid) from New Zealand and are spreading thin layers of it on their scalps - either before or after applying Crinagen. We don't know what success they are having. We have not had sufficient feedback from these subjects at this point. Because 20% azelaic acid is a very potent strength, we are suggesting that these people use it only with a physician's supervision. At the very least, they should consider diluting the 20% azelaic acid to 5% or less by mixing it with neutral creams.

Abstract of Stamatiadis' 1988 study:

Br J Dermatol 1988 Nov;119(5):627-632 Inhibition of 5 alpha-reductase activity in human skin by zinc and azelaic acid.

Stamatiadis D, Bulteau-Portois MC, Mowszowicz I

Laboratoire de Biochimie B, Hopital Necker-Enfants-Malades, Paris, France.

The effects of zinc sulphate and azelaic acid on 5 alpha-reductase activity in human skin were studied using an in vitro assay with 1,2[3H]-testosterone as substrate. When added at concentrations of 3 or 9 mmol/l, zinc was a potent inhibitor of 5 alpha-reductase activity. At high concentrations, zinc could completely inhibit the enzyme activity. Azelaic acid was also a potent inhibitor of 5 alpha-reductase; inhibition was detectable at concentrations as low as 0.2 mmol/l and was complete at 3 mmol/l. An additive effect of the two inhibitors was observed. Vitamin B6 potentiated the inhibitory effect of zinc, but not of azelaic acid, suggesting that two different mechanisms are involved. When the three substances were added together at very low concentrations which had been shown to be ineffective alone, 90% inhibition of 5 alpha-reductase activity was obtained. If this inhibition is confirmed in vivo, zinc sulphate combined with azelaic acid could be an effective agent in the treatment of androgen related pathology of human skin.

PMID: 3207614, UI: 89087983

The reservations one might have regarding the Stamatiadis study are (1) that the study was done on rats, (2) that is was done on prostate tissue (and not on hair tissue) and (3) that it was done "in vitro" (essentially means, "not in a living organism"). Cells in living tissue generally show a considerable ability to protect themselves from invasion. Treating pure 5-AR directly with azelaic acid in a lab flask is somewhat different from exposing the living cell to azelaic acid. Nevertheless, what happens "in vitro" often reveals clues as to what might happen "in vivo" (in a living organism).

In recent published research, Takahashi et al examined 1,000 different plant products to determine if any of them could influence hair growth. They determined that proanthocyanidins extracted from grape seeds promoted the prolieferation of hair cells by 230%. They also determined that proanthocyanidins converted the telogen (non-growing) phase of hair growth into the anagen (growing) phase of hair growth. In this experiement, proanthocyanidins displayed hair-cycle-converting activity which was similar to that of minoxidil. At the end of their report, the authors say that "WE are now investigating the possibility of the use of proanthocyanidins as agents for curing androgenic alopecia."

Two of the most powerful ingredients of Crinagen^TM are zinc and saw palmetto. Both agents have been shown to block the conversion of male sex hormones (such as testosterone) into dihydrotestosterone. Dihydrotestosterone is a potent hormone. Most researchers believe it is responsible for male-pattern hair loss. The ingredients in Crinagen^TM accomplish this by blocking the enzyme 5 alpha-reductase, which is required to produce dihydrotestosterone. Since the ingredients contained in Crinagen^TM are all natural ones, there are no hormonal side effects. The hallmark of male-pattern hair loss is the progressive miniaturization of hair follicles. This is caused by a genetic predisposition of individual hair follicles that renders them more sensitive to normal circulating levels of male sex hormones. This is because increased levels of 5 alpha-reductase in these follicles causes the conversion of male hormones (such as testosterone) into dihydrotestosterone. Dihydrotestosterone continues to damage and miniaturize hair follicles. As hair follicles are continually damaged by the ongoing effects of dihydrotestosterone, the body responds to this injury with an inflammatory response which is primarily mediated by the immune system. The cells of the immune system cause inflammatory reactions which further damage these hair follicles and eventually destroy them.

The best way to stop the progression of androgenic alopecia is to correct the underlying genetic defect that causes it. Unfortunately, gene therapy is not yet possible. The next best solution is to block the formation of dihydrotestosterone. Most researchers believe that this hormone is responsible for the progressive miniaturization of hair follicles, which is the hallmark of androgenic alopecia. One of the actions of Crinagen^TM is to block the activity of 5 alpha-reductase and, thereby, its ability to convert testosterone into dihydrotestosterone. In this manner, it reduces the amount of dihydrotestosterone within the scalp. Reducing the amount of dihydrotestosterone reduces its miniaturizing effects on the hair follicle. It also reduces the amount of injury it causes to the hair follicle and also the extent of the immune response targeted to the hair follicle. I recommend the use of immunosuppressant agents in conjunction with Crinagen^TM because, although Crinagen^TM may reduce the quantity of dihydrotestosterone, it does not completely reverse the damage to hair follicles that has already occurred. These damaged hair follicles incite an immune system inflammatory response which can damage them even further. The use of immunosuppressants can reduce this inflammatory reaction and, thus, subsequent damage to hair follicles. In Conquering Hair Loss there is a complete discussion of the inflammation/hair loss connection. There is also a complete discussion of the different types of immunosuppressive agents.

Crinagen^TM differs from other topical scalp preparations in that it is sold by itself, without an accompanying shampoo. The reason for this is that effective shampoos already exist. Dr. Razack recommends ones that are anti-inflammatory, such as Nizoral® (trademark name, Janssen Pharmacetica) or T-Gel® (trademark name, Neutrogena). Of these two, Nizoral® shampoo is probably a more effective immunosuppressant, but note that it is a prescription drug. As such, its dose, application frequency, and duration of use must be approved and monitored by a physician.

To prevent the inflammatory reaction to the scalp from occurring , the source of damage to the hair follicles must be eliminated. Again, dihydrotestosterone is the source of this injury, by causing the progressive miniaturization of hair follicles. Crinagen^TM contains both zinc and saw palmetto, which reduce the production of dihydrotestosterone by inhibiting the enzyme 5 alpha-reductase (discussed in Chapters 7, "Zinc", and 11, "Nutrition and Hair" in Conquering Hair Loss©). In addition, it contains vitamin B6, which has been shown to work in concert with zinc to inhibit 5 alpha-reductase (discussed in greater detail in Chapter 7, "Zinc").

Nutritive blood flow to the hair follicles is another factor that has been shown to regulate hair growth. Crinagen^TM contains both polysorbate 20 and niacin, which cause the release of histamine. Histamine mediates the immediate (vascular) response of inflammation thought to be beneficial for hair growth (discussed in greater detail in Chapter 5, "Inflammation and Hair Loss"). In addition, Crinagen^TM contains Ginkgo biloba, which has been shown to affect the amount of blood delivered to the hair follicle (discussed in greater detail in Chapter 11, "Nutrition and Hair"). Follicular size is directly correlated with blood supply: the larger the blood vessels that supply it, the larger the follicle will be. By affecting the blood supply to the hair follicle, we can hopefully increase its size. The result would be to reverse the miniaturization of hair follicles by dihydrotestosterone.

A full discussion of the benefits of Crinagen can be found in the book "Conquering Hair Loss".  

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Dr. Razack
Raztec, Inc.
P.O. Box 3891
Charlottesville, VA 22903-0891
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