IMPORTANT NEW RESEARCH INFORMATION FOR PROKARIN™ PATIENTS
This information may be beneficial for everyone since studies show that the general population is deficient in zinc. As we age, a zinc deficiency may occur because of the decrease in melatonin. Melatonin is necessary for zinc absorption. Research also shows that low levels of Zinc desensitize the H2 receptors. Possibly everyone should be receiving 25-35 mg of zinc a day.

Prokarin™ patients should not need supplementation of melatonin in order to absorb the zinc because histamine stimulates melatonin production.

Recap of supplements and diet for Procarin™ patients:

• Minimum of 1500 mg of calcium with 700-750 mg of magnesium per day. Be sure to take this with meals.
• Multivitamin and mineral supplement per day
• Vitamin B12 1000 mcg per day oral or sublingual
• Zinc 25-35 mg per day
• NO Essential Fatty Acid Supplements such as flaxseed oil, primrose oil, borage, fish oils, or omega 3 or 6.
• NO Co-enzyme 10
• NO licorice root
• NO low fat diet
• Eat at least 1 serving of red meat every other day or preferably every day and some butter such as a pat of butter on vegetables every day.

The reason the Dr. Swank low fat diet showed benefit maybe because a deficiency in histamine impairs fat and protein digestion and fat metabolism. Histamine stimulates the production of gastric acid and digestive enzymes, which are necessary for protein and fat digestion (Baer & Williams, 1992). The inadequate secretion of gastric acid and digestive enzymes due to a histamine deficiency results in the body becoming more dependent on carbohydrates for its energy. Thus, high total cholesterol may be common in histamine deficient patients because the body makes cholesterol from carbohydrates. Furthermore, the majority of cholesterol is made in the cell membranes, which acts as a stiffening agent used to balance the ratio of unsaturated to saturated fats in the cell membranes (Erasmus, 1986). Interestingly, a study by Mensink et al in 1992 showed that the medial level of serum lipoprotein[a] was lower in a saturated fat diet than in a cis-unsaturated or trans-unsaturated fat diet. An impaired fat metabolism due to a histamine deficiency may add to a high cholesterol production.

Histamine stimulates the production of melatonin by stimulating the activity of the pineal gland (Nowak & Sek, 1994). Melatonin is essential in fat metabolism as the pineal gland is the only area in the brain that can metabolize polyunsaturated fats by lipid oxygenation, whereas all other areas of the brain can only metabolize these fats via lipid peroxidation (Kim et al, 1999; Sawazaki et al, 1994). The impaired fat metabolism resulting from a deficiency of melatonin caused by a histamine deficiency may result in stress on the body. This stress increases the need for histamine because histamine is a major stress regulator for the body (Ghi et al, 1992). The increased demand for histamine contributes to a worsening/progression of symptoms if the person is already deficient in histamine.

Supplementing histamine through the administration of Prokarin™ can increase melatonin secretion as well as increase gastric acid and digestive enzyme production, which enhances fat and protein digestion and fat metabolism. Increased fat metabolism requires adequate fat intake to replenish the necessary fats. If the fat intake is inadequate, a person can experience severe weakness as well as neurological symptoms since the majority of the myelin and nervous system is composed of fats called phospholipids. It is imperative that the dietary fat intake is a balance of saturated and unsaturated fats. Research studies show that diets high in unsaturated fats and low in saturated fats result in increased lipid peroxidation. Lipid peroxidation is toxic to the cell membranes. The myelin and nerve cell membranes are very vulnerable to the cytotoxic effects of lipid peroxidation (Smith et al, 1999; Mazierre et al, 1999; Berry et al, 1991; de Kok et al, 1994; Fang et al, 1996; Fernstrom 1999).

Most of the medical community is aware of the increased risk of cancer. Oxidation of the double bonds in unsaturated fats results in an increase in free radicals, so antioxidant supplements are recommended when supplementing unsaturated essential fatty acids, such as Omega-3 and 6, flaxseed oil, primrose oil, borage oil, and fish oils. The problem with this according to studies, such as Alam et al in 1989 and Syburra &Passi in 1999, is that unsaturated dietary fat can lower the level of beta-carotene and other antioxidants including enzymatic ones circulating in the plasma.

It has been shown in research by Bougnoux 1999 & Maehle et al 1999, that the unsaturated fats particularly omega 3 are cytotoxic to tumor cells because of their lipid peroxidation properties. Unfortunately the cytotoxicity of the unsaturated fat is not selective so all cells, cancerous and healthy, can be destroyed by the lipid peroxidation. In fact research by Smith et al 1999, explains that oligodendrocytes (the myelin producing cells of the CNS) are more sensitive to oxidative stress from lipid peroxidation than other cells of the nervous system. Thus lipid peroxidation can result in selective oligodendrocyte death.

The risk of cancer from the effects of lipid peroxidation from unsaturated fat metabolism is further increased by the immunosuppressive effect of unsaturated fats. Unsaturated fats exhibit an anti-inflammatory effect. Inflammation is an integral part of the immune response. Studies show that the N-3 unsaturated fatty acid exhibits a suppressive effect on the cytokines of the immune system – IL-1, IL-2, IL-6, IL-10, IL-12, TNF-alpha, PGE2, TXB2, and LTB4. These serum levels of these cytokines were further reduced by Vitamin E supplementation used in conjunction with N-3 fatty acid (Venkatraman & Chu, 1999; Meydani et al, 1991). Furthermore the study by Meydani et al 1991 showed long term (N-3) fatty acid supplementation reduced lymphocyte proliferation in older women (51-68 yr). Thus the combined effect of lipid peroxidation and immune suppression exerted by unsaturated fats could be detrimental to one’s health. Any patients who have a suppressed immune system and / or a demyelinating disease are possibly more prone to the detrimental effects of a diet high in unsaturated fats.

References
Baer, C. L., & Williams, B. R. (1992). Clinical pharmacology and nursing (2nd ed.) Springhouse, PA: Springhouse. Erasmus, Udo (1986).

Fats that Heal Fats that Kill Burnaby, BC Canada: Alive Books. Mensink, R. P., Zock, P. L., Katan, M.B., & Hornstra, G. (1992, October).

Effect of dietary cis and trans fatty acids on serum lipoprotein [a] levels in humans. Journal of Lipid Research, 33(10), pp 1493-1501.

Nowak, J. Z., & Sek, B., (1994, June). Histamine is a powerful stimulator of cyclic AMP formation in chick pineal gland. Agents Actions, 41(special conference issue), pp. C60-C61.

Kim, H. Y., Edsall, L., Garcia, M., & Zhang, H., (1999). The release of polyunsaturated fatty acids and their lipoxygenation in the brain. Adv Exp Med Biol, 447, pp. 75-85.

Sawazaki, S., Salem, N. Jr., & Kim, H. Y., (1994, June). Lipoxygenation of docosahexaenoic acid by the rat pineal body. Journal Neurochemistry, 62(6), pp. 2437-2447.

Ghi, P., Blengio, M., Ferretti, C., & Portaleone, P. (1992, February). Stress and brain histaminergic system: Effects of weak electric foot shock. Pharmacology, Biochemistry, and Behavior, 41(2), pp. 317-320.

Smith, K. J., Kapoor, R., & Felts, P. A., (1999, January). Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathology, 9(1), pp. 69-92.

Maziere, C., Conte, M. A., Degonville, J., Ali, D., & Maziere, J. C., (1999, November). Cellular enrichment with polyunsaturated fatty acids induces an oxidative stress and activates the transcription factors AP1 and NfkappaB. Biochem Biophys Res Commun, 265(1), pp 116-122.

Berry, E. M., Eisenberg, S., Haratz, D., Friedlander, Y., Norman, Y., Kaufmann, N. A., & Stein, Y., (1991, April). Effects of diets rich in monosaturated fatty acids on plasma lipoproteins- the Jerusalem Nutrition Study: high MUFAs vs high PUFAs. American Journal of Clinical Nutrition, 53(4), pp. 899-907.

De Kok, T.M., ten Vaarwerk, F., Zwingman, I., van Maanen, J.M., & Kleinjans, J.C., (1994, July). Peroxidation of linoleic, arachidonic and oleic acid in relation to the induction of oxidative DNA damage and cytogenic effects. Carcinogenesis, 15(7), pp. 1399-1404.

Fang, J.L., Vaca, C.E., Valsta, L.M., & Mutanen, M., (1996, May). Determination of DNA adducts of malonaldehyde in humans: effects of dietary fatty acid composition. Carcinogenesis, 17(5), pp. 1035-1040.

Fernstrom, J.D., (1999, February). Effects of dietary polyunsaturated fatty acids on neuronal function. Lipids, 34(2), pp. 161-169.

Alam, B.S., Alam, S.Q., Bendich, A., & Shapiro, S.S., (1989). Effect of dietary lipids on hepatic and plasma beta-carotene and vitamin A levels in rats fed beta-carotene. Nutrition and Cancer, 12(1), pp. 57-60.

Syburra, C., & Passi, S., (1999, May-June). Oxidative stress in patients with multiple sclerosis. WMJ, 71(3), pp. 112-115.

Bougnoux, P., (1999, March). N-3 polyunsaturated fatty acids and cancer. Current Opinion of Clinical Nutrition and Metabolism Care, 2(2), pp. 121-126.

Maehle, L., Lystad, E., Eilertsen E., Einarsdottir, E., Hostmark, A.T., & Haugen, A., (1999, May-June). Growth of human lung adenocarcinoma in nude mice is influenced by various types of dietary fat and vitamin E. Anticancer Research, 19(3), pp. 1649-1655.

Venkatraman, J.T., & Chu, W.C., (1999, December). Effects of dietary omega-3 and omega-6 lipids and vitamin E on serum cytokines, lipid mediators and anti-DNA antibodies in a mouse model for rheumatoid arthritis. Journal of American College of Nutrition, 18(6), pp. 602-613.

Meydani, S.N., Endres, S., Woods, M.M., Goldin, B.R., Soo, c., Morrill-Labrode, A., Dinarello, C.A., & Gorbach, S.L., (1991, April). Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. Journal of Nutrition, 121(4), pp. 547-555.