Introduction to Vitamin Section
From: Cancer Therapy
© 1992 by Ralph W. Moss, Ph.D.
Vitamin A was the Þrst vitamin to be isolated and deÞned. It is a fat-soluble food factor that gives us the power of night vision. It also fortiÞes the mucous membranes, which serve as a barrier against poisons, microbial invaders and carcinogens (cancer-causing substances). It protects the thymus gland (crucial for immunity) and is essential for protein synthesis and normal growth. Like other powerful food factors, it is an antioxidant that destroys harmful chemicals called 'free radicals.' And it does much more.
Evidence for a link between vitamin A deÞciency and cancer goes back over 60 years. It was Þrst named in 1922. In 1926, a Japanese scientist found that laboratory animals deÞcient in vitamin A were more likely to develop cancer than those fed normal chow. Two years later, scientists found that a lack of vitamin A was an important factor in the development of human cancer, as well.
Around the same time, a Harvard researcher pointed out the similarity between vitamin A-deprived and cancer cells. After World War II, it was found that vitamin A enhanced the effectiveness of chemotherapy.
In 1963, vitamin A was Þrst shown to cure and prevent a condition called leukoplakia--white, warty patches in the mouth that often precede cancer. Dr. Umberto SafÞoti, dean of vitamin A studies, showed that mice could be protected against cancers of the lungs, stomach, gastrointestinal (GI) tract and uterus that were caused by carcinogens.
Sometimes the protection was nearly 100 percent.
By 1981, there were more than 300 positive reports on vitamin A. In that year, a well-known British researcher suggested that a diet high in carrots and similar vegetables could reduce the risk of cancer.
"I believe there is now a light at the end of our tunnel in our Þght against this disease," Dr. Richard Peto told a conference. He claimed there was a 40 percent lower risk of cancer among men who maintained above average consumption of vitamin A. Later, these studies were extended to A¹s non-toxic pro-vitamin, beta-carotene.
At Stockholm's Karolinska Hospital, scientists gave healthy subjects vitamin A pills. After a few years they found that vitamin A decreased the risk of cancer: the higher the dose, the less cancer developed. The Swedish scientists concluded that vitamin A may trap cell-damaging chemicals called free radicals and neutralize their cancer-causing effects. (They also found an increased risk of cancer in people who ate a lot of fried meat, fried potatoes or fat.) (1)
For ten years scientists at the NCI 'followed' (studied over time) nearly 2,500 men over the age of 50. Eighty-four of these men developed cancer of the prostate. Levels of vitamin A in their blood were found to be signiÞcantly lower than among men who did not develop this cancer. In fact, the lower their blood serum level of vitamin A, the greater their risk of developing prostate cancer. This was the Þrst time that vitamin A and prostate cancer were subjected to a large Œprospective¹ study (in which scientists select a group of people and then check up periodically to see what diseases they have developed) (2).
In another NCI study, blood was obtained in 1974 from over 25,000 people. Over 100 of these developed prostate cancer during the next 13 years. Once again, the less vitamin A (retinol) they had in their blood, the greater their odds of developing prostate cancer (3).
Six hospitals in southwestern France provided 106 cases of lung cancer for a dietary study. As with prostate cancer, it was found that the lower the consumption of vitamin A and its pro-vitamin, beta-carotene, the greater the chances of developing lung cancer.
French scientists conÞrmed the protective value of beta-carotene and provided new evidence that vitamin A also has a protective effect. In experimental animals,
cancer forms in two phases‹initiation and promotion.
This vitamin seemed to inhibit the tumor promotion phase, while beta-carotene complemented this action by inhibiting tumor initiation (4).
Dutch scientists have studied the blood levels of vitamin A in 86 patients with cancers of the head and neck. Some of these patients had tumors at other sites as well. Thirty-one percent of the patients with just head and neck cancers had low serum levels of vitamin A. But 60 percent of those with two kinds of cancer had low levels. About two-thirds of all these cancer patients had low beta-carotene levels.
The scientists concluded that it was possible that low vitamin A levels play a role in causing a second tumor of the head or neck. They recommended that patients with head and neck tumors be given vitamin supplements in order to prevent a second tumor from forming (5).
In early 1992, Italian scientists reported that a combination of vitamin A with vitamins C and E could correct abnormalities in the cells of the rectum in people who had had polyps removed. Such abnormalities are believed to eventually progress to cancer in many cases. They reported their Þnding in the Journal of the National Cancer Institute (JNCI). The Bologna scientists found a decrease in the occurrence of malignant-type cells in patients who received the three vitamins, compared to controls. As an interesting side light, the patients in this study were given relatively high doses of vitamin A--25,000 to 50,000 IU per day for months. There were "no side effects" in the population studied, non-pregnant adults without liver problems (6).
Vitamin A is one of those few fat-based vitamins that is toxic in high doses (others are vitamins D, E and K).
A variant of vitamin A used in cancer therapy is the acne medication, Accutanet (13-cis-retinoic acid). This is not entirely non-toxic. Like vitamin A, when taken in excess, it can cause extremely dry skin, chapped lips, eye problems (conjunctivitis) and increased levels of fat in the blood.
Frank L. Meyskens, Jr., MD, is a prominent researcher at the University of California (UC), Irvine who has been studying vitamin A and its derivatives, called retinoids, for a dozen years. He has found them beneÞcial for some kinds of cancer.
"I think increasingly, we will Þnd the retinoids in and of themselves will impact the prevention and treatment of cancer," he has said. For example, a rapidly growing kind of skin cancer (keratoacanthoma) responds to the retinoid-like Accutane.
In 1985, Dr. W.K. Hong of the Head, Neck and Thoracic Oncology Department at M.D. Anderson Cancer Center proposed the experimental use of Accutane in treating head and neck cancer (7). In the New England Journal of Medicine in 1990, he reported positive results using Accutane to treat tumors. M.D. Anderson scientists studied 103 patients who were disease-free after receiving standard treatment for cancers of the larynx, pharynx or the mouth. After receiving surgery or radiotherapy or both, they were assigned to receive either Accutane or a placebo (sugar pill), which they took daily for 12 months.
While there were no differences between the two groups in the number of recurrences of the primary cancers, the group receiving Accutane had ³signiÞcantly fewer second primary tumors.² After 32 months, only 2 patients (4 percent) in the Accutane group had second primary tumors, compared with 12 (24 percent) in the placebo group. Some of those in the placebo group had multiple cancers reappear. Of the 14 second cancers, 13 (or 93 percent) occurred in the head and neck, esophagus or lung, the Houston researchers said.
These scientists concluded that "daily treatment with high doses of Accutane is effective in preventing second primary tumors in patients who have been treated for squamous-cell carcinoma of the head and neck, although it does not prevent recurrences of the original tumor" (8).
Another variant on the vitamin (transretinoic acid) when topically applied beneÞtted a condition called dysplastic nevi syndrome, which can turn into the deadly skin disease, malignant melanoma. Some other advanced skin cancers and a kind of lymphoma of the skin have also shown beneÞt with this therapy. One patient had 30 skin cancer cell growths on his hands and was scheduled to have both hands amputated. He showed such tremendous improvement on Accutane that the surgery was called off and he has remained free of the disease for years.
By placing Accutane directly in cervical caps (a barrier form of birth control) doctors have been able to get an 80 percent response to moderate cases of cervical dysplasia. (Beta-carotene and the B vitamin folate also beneÞt this condition.)
Negative: Scientists at the Evans Department of Clinical Research of University Hospital, Boston, MA studied the effect of Accutane on a wart-like condition called ³respiratory papillomatosis.² They used it as an adjuvant (helper) treatment to surgery with lasers. Four of the six patients experienced a recurrence while using the therapy, and so the study was discontinued (9).
Conclusion: Vitamin A and its derivatives are being proposed as "chemopreventive" agents. The biochemistry of vitamin A suggests a number of ways in which it could decrease the chance of cancer even getting started. Scientists are generally cautious about telling people to take supplements, especially since high doses of vitamin A can be toxic. But many concede that greater intake of beta-carotene and vitamin A-rich foods may be a Œprescription¹ worth following (10).
1. Steineck G, et al. Vitamin A supplements, fried foods, fat and urothelial cancer, a case-referrent study in Stockholm in 1985-1987. International Journal of Cancer.1990; 45:1006-1011.
2. Reichman M, et al. Serum vitamin A and subsequent development of prostate cancer in the Þrst national health and nutrition examination survey epidemiologic follow-up study. Cancer Research. 1990; 50:2311-2315.
3. Hsing A, et al. Serologic precursors of cancer. Retinol, caro-tenoids and tocopherol and the risk of prostate cancer. J Natl Cancer Inst.1990;82:941-946.
4. Dartigues J, et al. Dietary vitamin A, beta-carotene and risk of epidermoid lung cancer in southwestern France. European Journal of Epidemiology.1990;6:261-265.
5. De Vries N and Snow G. Relationship of vitamins A and E and beta-carotene serum levels to head and neck cancer patients with and without second primary tumors. European Archives of Otorhinolaryngol.1990;247:368-370.
6. Paganelli G, et al. Effect of vitamin A, C, and E supplementation on rectal cell proliferation in patients with colorectal adenomas. J Natl Cancer Inst.1992;84:47-51.
7. Hong WK and Doos WG. Chemoprevention of head and neck cancer. Potential use of retinoids.Otolaryngol Clin North Am.1985; 18:543-9.
8. Hong WK, et al. Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck [see comments]. N Engl J Med.1990;323:795-801.
9. Bell R, et al. The use of cis-retinoic acid in recurrent respiratory papillomatosis of the larynx: a randomized pilot study. Am J Otolaryngol.1988;9:161-4.
10. Kummet T, et al. Vitamin A: evidence for its preventive role in human
cancer. Nutr Cancer.1983;5:96-106.
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