Appendix A

Avoiding Vitamin A Toxicity

Based upon hundreds of published studies, the Life Extension Foundation has recommended vitamin A analog drugs to cancer patients. For the many cancer patients who cannot gain access to vitamin A analogs because the FDA classifies them as "unapproved new drugs," the Foundation has recommended the use of water-soluble vitamin A liquid drops.

The dosage range of vitamin A liquid drops that cancer patients have been using is 100,000-300,000 IU a day. The Foundation has cautioned that these high doses could produce toxicity if taken over extended periods of time, yet cancer patients often are forced to risk some degree of toxicity to obtain an effective dose of vitamin A.

Vitamin A and BoNE

Reports of increased bone fracture risk are a concern when higher potency vitamin A supplements are taken over the long-term (Michaelsson et al. 2003). One study showed bone mineral density was reduced by 10 percent in those taking more than 5000 IU of vitamin A from both dietary sources and supplements. This study showed that compared to lower intakes of vitamin A, those taking more than 5000 IU of vitamin A had a 2.1 time higher risk of hip fracture.

One reason people take vitamin A supplements is to reduce cancer risk. What these bone density/fracture studies fail to ascertain is whether the same people taking higher doses of vitamin A had lower incidences of cancer. These studies also fail to establish whether the study participants were taking adequate amounts of bone-protecting nutrients such as manganese, zinc, copper, vitamin K, and magnesium. It could be that people consuming lots of vitamin A-fortified milk and eating vitamin A-rich organ meats had deficiencies of other nutrients critical to bone maintenance. One of these nutrients is folic acid, which lowers homocysteine levels. Excess homocysteine participates in degenerative bone degradation.

From a practical standpoint, a healthy person is left with some unanswered questions. A plethora of published studies associates low vitamin A intake with increased cancer risk (see Reference list for Appendix A). Guarding against vitamin A deficiency is thus a critical component of a cancer prevention program. It would therefore appear practical to supplement with 5000 IU a day of vitamin A, but perhaps higher doses are not needed. In fact, taking higher doses of vitamin A over an extended time period without other bone-protecting nutrients would appear to increase fracture risk. Refer to the Osteoporosis protocol for complete details about the steps you can take to protect against the loss of bone mineral density and subsequent risk of fracture.

Concerns for Cancer Patients
Cancer patients often take high potencies of vitamin A drugs, such as Vesanoid (all-trans retinoic acid), Accutane (13-cis-retinoic acid) or vitamin A supplements. These vitamin A drugs have potent anti-proliferative, differentiation-inducing, and apoptosis-promoting effects against cancer cells.

Retinoic acid (a potent vitamin A drug) has been shown to suppress osteoblast activity (bone-building cells) and promote formation of osteoclasts (cells that remove old bone) in vitro (test tube studies).

Depletion of bone mineral density is of concern to cancer patients, since some cancer drugs also cause bone mineral depletion. Some cancers have a proclivity to metastasize to bone, and weakened bones may be more vulnerable to cancer cell adhesion and infiltration. Beta-carotene does not induce any loss of bone density, but it fails to exert the same potent effects against existing cancer cells as vitamin A drugs.

Cancer patients taking high potencies of vitamin A drugs or supplements should pay particular attention to the "Maintaining Bone Density" section of the protocol entitled Cancer: The Critical Factors. This section describes the steps that cancer patients should take to maintain bone integrity.

Anyone taking very high doses of vitamin A for cancer or any other reason should do so under the care of a physician and should be on the lookout for symptoms of vitamin A toxicity. The following are common symptoms of vitamin A overdose that should be watched for in cancer patients taking high doses of any vitamin A product:

• Headache
• Dizziness
• Blurred vision
• Joint pain
• Dry lips
• Scaly, dry skin
• Excessive hair loss

Blood tests showing elevated liver enzymes may be a sign of a vitamin A overdose. If any of these symptoms appear, discontinue using vitamin A until the symptoms disappear, and then resume vitamin A therapy at a much lower dosage. The cancer patient faces a dilemma in attempting to use the maximum dose of vitamin A to fight his or her cancer, while trying to avoid vitamin A toxicity.

The thyroid gland works with the liver to produce a vitamin A binding protein called transthyretin. This keeps vitamin A bound in the blood and only releases it to the body when needed. When there is no thyroid gland, the lack of transthyretin makes high doses of vitamin A potentially toxic because there is no control mechanism to hold the vitamin A in a biologically unavailable form. Therefore, those with thyroid cancer should avoid vitamin A.