By Dr. Mercola
During a recent clinical trial, scientists found a possible link between retinoic acid, a compound produced in your body from vitamin A, and the inhibition of colon cancer, one of the leading causes of cancer worldwide.
In a Philly.com article, Dr. Edgar Engleman, professor of pathology and medicine at Stanford University School of Medicine, said scientists have known for years that retinoic acid is involved in suppressing inflammation in the intestine, but his team wanted to "connect the dots" to figure out how it relates to cancer development.
In the initial studies, published in the journal Immunity, the researchers found lower levels of retinoic acid in mice with colon cancer.1 Then they discovered that when the intestines of the mice with colon cancer were given an extra dose of retinoic acid, the disease's progression slowed down.
However, as the article noted, "animal research doesn't always produce the same results in humans." As Engleman explained:
"The intestine is constantly bombarded by foreign organisms. As a result, its immune system is very complex. We found that bacteria, or molecules produced by bacteria, can cause a massive inflammatory reaction in the gut that directly affects retinoic acid metabolism."2
When scientists discovered that high levels of a certain protein broke down retinoic acid in the intestinal tissue of colon cancer patients, rendering it inactive, those patients tended to have "worse outcomes" than other patients. According to Engleman:
"Now that we've shown a role for retinoic acid deficiency in colorectal cancer, we'd like to identify the specific microorganisms that initiate these changes in humans. Ultimately we hope to determine whether our findings could be useful for the prevention or treatment of colorectal cancer."3
Colon Cancer Relapses and HOXA5
In theory, as Science Daily explains, when patients with colon cancer undergo chemotherapy treatments, most of the cancer cells are killed. However:
"The genetic mutations that caused the cancer in the first place can survive in a specific group of cells of the colon. These are actually stem cells, meaning that they are premature cells waiting to grow into full-blown, normal cells of the colon.
After cancer treatment ends, the surviving stem cells, still containing the cancerous mutations, can reappear and cause a relapse."4
At the Swiss Federal Institute of Technology in Lausanne (EPFL), studies by Joerg Huelsken's team found that in the gut, the protein identified as HOXA5 plays a major role in restricting the number of stem cells, as well as the cells that make them.5
Scientists focused on the high levels of HOXA5, part of a family of proteins with the job of regulating early fetus development, making sure tissues are patterned correctly and work together as they should. In adults, similar proteins regulate stem cells to maintain the function and identity of tissues.
So HOXA5, which comes from a specific gene, determines to some degree how many stem cells develop. Colon cancer stem cells use a biological mechanism, or signaling pathway, to block HOXA5. One molecule activates another, which activates the next one, in a domino effect. According to Science Daily:
"The purpose of a signaling pathway is to transmit biological information from one part of the cell to another, e.g. from the outer membrane all the way to the nucleus. By blocking the HOXA5 gene, the cancerous stem cells of the colon can grow uncontrollably and spread, causing relapses and metastasis."6
The EPFL researchers looked for ways to reverse cancer stem cells' ability to block HOXA5 and found that retinoids can reactivate it. As explained in Science Daily:
"In mice that had colon cancer, the treatment with retinoids blocked tumor progression and normalized the tissue.
By turning the gene for HOXA5 back on, this treatment eliminated cancer stem cells and prevented metastasis in the live animals. The researchers got similar results with samples from actual patients."7
The EPFL scientists hope their study is the pivotal point upon which "retinoid differentiation therapy" can change the deadly course of colon cancer, not only for existing patients but as a preventative measure for future ones.
Studies Show Abundance of Evidence: Vitamin A Helps Fight Cancer
Not so long ago, some scientists believed vitamin A actually caused cancer, even while acknowledging it to be "necessary for embryonic development precisely because it helps to 'differentiate' stem cells, pushing them to become required tissue," according to an article in Orthomolecular.org.8
Then a study conducted in 1926 brought about what may have been the first link indicating that vitamin A might inhibit cancer. It was simple: Rats fed a diet low in vitamin A developed stomach cancer. In 1941, a focused study involving humans with the same cancer found they had low vitamin A levels.
This outcome was similar to what Engleman found 75 years later. Perhaps it was those early forays into vitamin A that tipped off scientists who found lower mesothelioma incidences in patients given retinol.9 Further, the Linus Pauling Institute reported:
"Studies in cell culture and animal models have documented the capacity for natural and synthetic retinoids to reduce carcinogenesis significantly in skin, breast, liver, colon, prostate and other sites."10
An anti-cancer drug called VN/14-1, which blocks the breakdown of retinoic acid, brought about nearly a 50 percent reduction in the sizes of tumors in mice implanted with human prostate cancer cells, and after five weeks no further tumor growth was detected.11
Another study found that working together, vitamins A and C applied to cultured breast cancer cells were more than three times more effective at inhibiting proliferation compared to untreated cells. According to the Journal of Nutritional Biochemistry:
"The ability of retinoic acid (vitamin A) to inhibit tumor cell proliferation is well known, although its mechanism has not been defined.
The authors suggest that the synergistic effect observed in this study is due to ascorbic acid's ability to slow the degradation of retinoic acid, thereby increasing vitamin A's cell proliferation inhibitory effects."12
In fact, vitamin A works synergistically with a number of other vitamins and minerals, including vitamins D and K2, zinc and magnesium, and without that cooperation, vitamin A can't work as it's supposed to.
Vitamin A: Retinoids and Carotenoids
Many people think that if they eat a lot of carrots and sweet potatoes, they're probably getting adequate vitamin A, but that's not necessarily the case. There are two different kinds of vitamin A: Bioavailable retinoids from animals; and carotenoids, found in plant-based foods.
According to the George Mateljan Foundation, which focuses on sharing scientifically proven information and helping people eat and cook for optimal health:
"These two forms aren't just chemically different — they also provide us with different types of health benefits. There are some specific immune, inflammatory, genetic and reproductive-related benefits of vitamin A that can only be obtained from the retinoid forms of the vitamin.
These retinoid forms can be especially important with respect to pregnancy and childbirth, infancy, childhood growth, night vision, red blood cell production and resistance to infectious disease. Yet even if we are not faced with any of these special conditions, each of us needs retinoid forms of vitamin A."13
You may have noticed that only the retinoid version of vitamin A is absorbable by your body. Conversely, your body needs to convert plant-based carotenoids into retinoids, but certain factors might prevent this process, such as:
✓ Alcohol use
✓ Certain foods
✓ A low-fat diet
✓ Exposure to toxicities
✓ Certain medications
✓ Medical conditions that prevent fat absorption
The bad news is this list comprises most people. While vitamin A deficiency isn't thought to be common in the U.S., it certainly is in developing countries. One of the first signs is night blindness, which can worsen if your vitamin A intake isn't increased.
Vitamin A: Good for Vision, Cell Growth, Neurological Function and More
Vitamin A is an antioxidant, so it helps fight inflammation and damage from free radicals. Between the retinoid and carotenoid vitamin A sources, benefits to your body include:
✓ Immune system function
✓ Gene regulation
✓ Cell differentiation
✓ Slowing the aging process
✓ Healthy vision
✓ Strong bones
✓ Neurological function
✓ Healthy skin
Good Sources of Vitamin A
The best way to "up" your vitamin A intake is through food. Eggs from organic, pastured chickens (especially raw, or as close to raw as possible), whole raw milk and cream from organic, grass-fed cows, and raw, organic butter and cheese from grass-fed cows are all excellent sources. Other foods containing high amounts of vitamin A include:
✓ Winter squash
✓ Mustard and collard greens
✓ Shrimp (be careful, as most shrimp are farm raised)
✓ Wild-caught Alaskan salmon
✓ Sweet potatoes
✓ Romaine lettuce
Vitamins and Minerals Are Necessary for Optimal Health
Incidentally, the Orthomolecular.org article also notes how often the nutritional benefits of foods are studied for the express purpose of developing drugs from them, rather than encouraging people to eat the foods that supply the nutrients, aka to "let food be your medicine and medicine your food."
"Sensational warnings and outright misstatements that natural vitamin A may 'incite' cancer actually serve to incite newspaper readers and television viewers. Upon closer examination, a 'vitamin promotes cancer' study often has the appearance of being conducted to prove an intended point.
As the authors fuel fears about vitamin A, they also give away their goal, in their own words stating that 'these findings open a new door to drug development.' New marketing avenues for the development of patentable vitamin A-like drugs are a commercial opportunity that the pharmaceutical industry has not overlooked."14