Selected Recent LPI Publications in Orthomolecular Medicine

Summarized by Stephen Lawson
LPI Administrative Officer

Photo of Stephen Lawson, LPI Administrative Officer

Infectious Diseases
Heart Disease
Neurological Disease
Cancer or Toxicology

Infectious Diseases

Hemilä, Harri and Herman, Zelek. Vitamin C and the common cold: a retrospective analysis of Chalmers' review. Journal of the American College of Nutrition, volume 14, number 2, pp. 116-123 (1995)

Drs. Hemilä and Herman examined the influential review of the efficacy of vitamin C against the common cold published by Dr. Thomas Chalmers in 1975, which they found to be seriously flawed due to data errors and the inclusion in Chalmers' analysis of a clinical study using only 25-50 mg/day of supplemental vitamin C. Using the correct data from the original publications, Drs. Hemilä and Herman found that supplemental vitamin C in doses from 1-6 grams/day significantly decreased both the duration and symptoms of the common cold.

Harakeh, Steve and Jariwalla, Raxit. Ascorbate effect on cytokine stimulation of HIV production. Nutrition (supplement), volume 11, number 5, pp. 684-687 (1995)

Drs. Harakeh and Jariwalla investigated the effects of vitamin C and AZT, a commonly prescribed AIDS drug, on the production of the human immunodeficiency virus (HIV) in cells stimulated with tumor necrosis factor alpha (TNF-a, an inflammatory cytokine. (Cytokines are small proteins that trigger cell differentiation or proliferation and also regulate the immune response.) TNF-a caused a very significant increase in viral production in control cells, as assayed by the amount of reverse transcriptase (RT), a viral enzyme whose amount correlates with viral replication. However; pretreatment of the cells with ascorbate significantly reduced the amount of extracellular RT indicating inhibition of viral replication, whereas AZT had no effect.

Jariwalla, Raxit. Micro-nutrient imbalance in HIV infection and AIDS: relevance to pathogenesis and therapy. Journal of Nutritional & Environmental Medicine, volume 5, pp. 297-306 (1995)

Dr. Jariwalla reviewed the causes and consequences of micronutrient imbalance in HIV-infected persons and AIDS patients. Abnormalities in micronutrient status due to malnutrition, oxidative stress, or malabsorption contribute to immunological impairment and AIDS-related pathologies. Dr. Jariwalla noted that prospective studies of asymptomatic HIV-infected persons indicate that micronutrient consumption or repletion may delay the onset of AIDS.

Jariwalla, Raxit and Harakeh, Steve. Antiviral and immunomodulatory activities of ascorbic acid. In Subcellular Biochemistry, Volume 25: Ascorbic Acid: Biochemistry and Biomedical Cell Biology, edited by J. Robin Harris, NY: Plenum Press, pp. 215-231 (1996)

Drs. Jariwalla and Narakeh reviewed the virucidal and immunostimulatory effects of vitamin C presented in scores of studies published in the last three decades. Vitamin C has been found to inhibit viral infectivity by inactivating viruses and by affecting viral replication. Additionally, vitamin C promotes immunological functions, such as phagocytosis, chemotaxis, and neutrophil adhesion, and acts as a powerful antioxidant, thereby alleviating oxidative stress engendered by viral infection. Ascorbate is also involved in the regulation or synthesis of crucial immune system molecules, such as cytokines, antibodies, and interferon. The authors cite numerous relevant animal, cell culture, and human studies and, on the basis of positive results of clinical studies using small amounts of supplemental vitamin C, conclude that more clinical studies are needed to determine the optimal therapeutic dose of vitamin C.

Harakeh, Steve and Jariwalla, Raxit. NF-kB-independent suppression of HIV expression by ascorbic acid. AIDS Research and Human Retroviruses, vol.13, number 3, pp. 235-239 (1997)

In this paper; the authors narrowed the focus on the molecular mechanism by which vitamin C inhibits HIV, a retrovirus, by determining that the inhibition by ascorbate occurs at a step after transcription of the viral genetic material, whereas other antioxidants inhibit HIV replication by blocking transcription. (In most organisms, DNA is transcribed into RNA, which then controls the synthesis of proteins, but in retroviruses, RNA is transcribed into DNA, which then becomes integrated into the host cell's genomic DNA.)

Jariwalla, Raxit and Harakeh, Steve. Mechanisms underlying the action of vitamin C in viral and immunodeficiency disease. In Vitamin C in Health and Disease, edited by Lester Packer and JÜrgen Fuchs, NY: Marcel Dekker, pp. 309-322 (1997)

This book chapter reviews the manifold mechanisms by which vitamin C exerts antiviral and immunostimulatory effects. Ascorbate potentiates the immune system, spares glutathione (an important intracellular antioxidant), combats oxidative stress, neutralizes extracellular free radicals liberated by immune cells in response to pathogens, selectively kills virally infected cells, suppresses viral replication, and directly inactivates viruses.


Heart Disease

Roomi, M. Waheed and Tsao, Constance. Effect of ascorbic acid deficiency on plasma prothrombin time and partial thromboplastin time in guinea pigs. Clinica Chimica Acta, volume 248, pp. 209-211 (1996)

Using guinea pigs, Drs. Roomi and Tsao determined the clotting, or coagulation, time for the plasma of guinea pigs fed different amounts of vitamin C. They found that ascorbic acid deficiency resulted in coagulation abnormalities, i.e. prothrombin time was increased and thromboplastin time was decreased, and that these defects were corrected by increasing the ascorbic acid intake.

Ivanov, Vadim; Ivanova, Svetlana; and Niedzwiecki, Aleksandra. Ascorbate affects proliferation of guinea pig vascular smooth muscle cells by direct and extracellular matrix-mediated effects. Journal of Molecular and Cellular Cardiology, in press (1997)

The proliferation of vascular smooth muscle cells (VSMC) and the proteins secreted by them into the extracellular matrix, which forms a structural lattice for cells, contribute to the development of atherosclerotic plaque. In cell culture experiments, the authors found that these events can be modified by high concentrations of vitamin C, which inhibit the proliferation of VSMC directly and indirectly by modifying the extracellular matrix deposited by VSMC. Vitamin E also inhibited DNA synthesis by VSMC, resulting in decreased cell proliferation, but did not alter the extracellular matrix.


Neurological Disease

Dunham, Wolcott; Tsao, Constance; Barth, Roger; and Herman, Zelek. Protection by dietary ascorbate of guinea pigs from neurolathyrism. Nutrition Research, vol. 15, pp. 993-1004 (1995)

Neurolathyrism, a paralytic disease caused by consumption of Lathyrus sativus, or the grass pea, is prevalent in many regions of the world. The grass pea provides protein and grows readily in areas of drought or flooding. However; the pea and its flour contain several neurotoxins, including B-N-oxalylamino-L-alanine (BOAA), that can cause paralysis in humans and guinea pigs, which, like humans, are unable to synthesize vitamin C and provide a good experimental model to study this disease. Dr. Dunham and his colleagues found that guinea pigs on an ascorbate-deficient diet given an injection of an extract of the pea containing BOAA died or exhibited paralysis, whereas guinea pigs supplemented with vitamin C were completely protected or showed only minor; transient weakness. These results may have important relevance to humans who rely on the grass pea for nutrition but succumb to its toxicity.

Roomi, M. Waheed and Tsao, Constance. Ascorbic acid protection of guinea pigs against B-aminopropionitrile induced neurolathyrism. Research Communications in Biological Psychology and Psychiatry, vol.20, numbers 3 and 4, pp.113-122 (1995)

To determine the mechanism of protection against neurolathyrism afforded by vitamin C, Drs. Roomi and Tsao compared the effect of two free-radical trapping agents, vitamin C and N-tert-butyl-a-phenylnitrone (BPN), on the neurotoxicity in guinea pigs of another neurotoxin, B-aminopropionitrile (BAPN), contained in the grass pea. Both free-radical scavengers protected the guinea pigs from neurolathyrism when given before or with BAPN, indicating that free radicals generated by the neurotoxin are probably responsible for the symptoms of the disease.


Cancer or Toxicology

Tsao, Constance; Dunham, Wolcott; and Leung; Ping. Growth control of human colon tumor xenografts by ascorbic acid, copper, and iron. The Cancer Journal, vol. 8, pp. 157-163 (1995)

The authors of this study previously reported that a combination of ascorbic acid and copper sulfate inhibited the growth of small fragments of human mammary or lung tumors explanted in mice. Fragments of the human tumors were implanted under the renal capsule of mice and measured after six days of treatment. This method allows for evaluation of the immune-independent anti-cancer effect of the test agents, since the immune system does not respond quickly to the xenograft. In another set of experiments reported in this paper, Drs. Tsao, Dunham, and Leung showed that the growth of human colon adenocarcinoma explants in mice was also inhibited by a combination of large amounts of ascorbic acid in the diet and copper or iron ions supplied in the drinking water. The administration of metal ions without vitamin C increased tumor growth, whereas vitamin C alone suppressed tumor growth in some animals. The combination of ascorbic acid and metal ions proved much more effective than the vitamin alone, indicating that the anti-cancer effect was due to products formed by the oxidation of vitamin C, which is catalyzed by the metal ions, rather than to its vitamin activity.

Tsao, Constance and Young, May. Molecular structure-dependent cytotoxic effect of ascorbate derivatives. In Vitro Cellular and Developmental Biology, volume 31, pp. 87-90 (1995)

In this letter, Dr. Tsao and Ms. Young suggest that the anticancer, cytotoxic effect of ascorbate derivatives and degradation products are dependent on the chemical structure, rather than the vitamin activity, of ascorbic acid. They compared the cytotoxic effect of derivatives of vitamin C formed by oxidation, other degradation products of vitamin C, and its isomers on mouse leukemia cells. Their results suggest that the cytotoxic moiety resides in the enediol lactone ring structure of the molecules. This line of research may suggest novel therapeutics for cancer treatment.

Roomi, M. Waheed and Tsao, Constance. Dietary ascorbic acid does not alter the expression of the 58-kDa acetaminophen binding protein nor the arylation of other cytosolic proteins in guinea pig liver. Research Communications in Pharmacology and Toxicology, volume 1, number 4, pp. 269-278 (1996)

Acetaminophen, an over-the-counter analgesic, is metabolized in a similar manner by most animal species. However; susceptibility to toxicity of acetaminophen overdose, which may result in liver necrosis, varies among species. Drs. Roomi and Tsao determined that the major protein in mouse and human livers that binds acetaminophen is not synthesized in guinea pigs, thereby providing the basis for additional studies to determine the mechanism involved in acute acetaminophen toxicity in guinea pigs and how this may be influenced by ascorbic acid.

Roomi, M. Waheed; Ogg, M.; Tsao, Constance; and Gibson, G. Ascorbic acid deficiency decreases the expression of CYP4A1 in liver microsomes of guinea pigs. Research Communications in Molecular Pathology and Pharmacology, volume 95, number 1, pp .3-10 (1997)

The cytochrome P-450 system is the main drug metabolizing system in humans. The activity of many of the enzymes comprising this system is affected by nutritional status, age, gender; and other factors. Dr. Roomi and his colleagues measured the amount of a particular cytochrome P-450, CYP4A1, which is induced in the liver by the hypolipidemic drug clofibrate, in guinea pigs. They found that the expression, or synthesis, of total cytochrome P-4S0 and of CYP4A1 decreased in ascorbic acid deficient animals, which may indicate less efficient detoxification of the drug.
Netke, Shrirang; Roomi, M. Waheed; Tsao, Constance; and Niedzwiecki, Aleksandra. Ascorbic acid protects guinea pigs from acute aflatoxin toxicity. Toxicology and Applied Pharmacology, volume 143, pp.429-435 (1997)

Aflatoxins are mycotoxins produced by molds that grow on grain and nuts. Their consumption is associated with liver damage and liver cancer in many regions of the world (see George Bailey's article in this issue). Dr. Netke and his colleagues gave an oral dose of aflatoxin B1 to guinea pigs fed diets containing no vitamin C or a small amount of vitamin C, or given a larger amount of vitamin C by mouth. 70% of the unsupplemented guinea pigs died, but all of the vitamin C-supplemented animals survived. The largest dose of vitamin C also protected the animals' livers from any pathological abnormalities. These results may be applicable to humans, who might be spared the misery of aflatoxin induced liver cancer.

Last updated November, 1997

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