Vitamins to Breast Cancer

This popular and vital topic is used as a Real Life example to show how difficult if is for Scientists to analyze the many factors that have to be considered when evaluating possible vitamin health connections.

Scientists have mountains of data to study to find connections. The interpretation of current research presents many challenges for the development of new health theories, especially when study results differ from existing mainstream health protocols.

First one lists discovered facts and associations gained from past research to see how they might fit together as puzzle pieces with new study results. Breast cancer connections are listed below as an example. These are just in most cases associations and not cause and effect facts. Work with your Medical team if you have this condition.

1. Breast cancer rates are slightly higher after menopause in women with increased bone density. ref ref
2. Calcium and vitamin D may increase bone density.
3. Weight-bearing exercise increases bone density and strength.
4. Overall, Exercise decreases breast cancer risk. ref  ref
5. Exercise increases available oxygen for cells and tissues.
6. Higher Magnesium levels, but not calcium, associated with better survival from breast cancer. ref
7. Higher estrogen levels maintain greater bone density
8. Higher estrogen levels are associated with greater breast cancer risk (estrogen positive cancers) ref
9. Since estrogen is built in fat tissue, this might be one way obesity is related to greater breast cancer risk, but blood sugar may also be a factor.
10. Drugs to slow bone turnover and bone growth reduce breast cancer rates, i.e. bisphosphonates like Fosamaxtm
11. Bone Hormone Osteocalcin levels are increased with higher bone turnover.
12. Osteocalcin helps regulate blood sugar and insulin levels (NEW).  ref
13. Osteocalcin is built by bone building cells under guidance of vitamin D.  ref  
14. In test tube studies, Vitamin D exhibits a biphasic role on osteocalcin production with opposite direction responses on vascular calcification at different vitamin D levels.*** ref
15. Osteocalcin exists in two forms, uncarboxylated (ucOC) and carboxylated (cOC).
16. Osteocalcin is built under vitamin D direction as uncarboxylated, after carboxylation by vitamin K2, Osteocalcin helps bind calcium into bones. article   ref
17. Breast cancer patients with higher levels of adiponectin, produced under direction of osteocalcin in fat cells, survived longer. ref  (Raspberry Ketone studies on animals show increased expression of adiponectin ref , still needs human verification)
18. The active hormone form of vitamin D inhibits Breast cancer cells from producing HAS-2, an enzyme that builds hyaluronic acid which cancer cells hijack (ref)and use to trigger inflammation and the building of new blood vessels to feed and grow tumors bigger, CD44 attaches to HA to accomplish this action. ref
19. Breast cancer patients often exhibit higher blood sugar levels and lower osteocalcin levels if bones are not involved, where in that case, osteocalcin levels are increased over normal.  ref  ref
20. Insulin and /or insulin growth factor (IGF-1) levels are elevated in breast cancers. ref  ref  ref
21. IGF-1 is increased in cows given the growth hormone rBGH, and thus in their milk too.
22. Cancer cells have numerous insulin receptors which feed off higher insulin levels to protect the cancer cells from anticancer drugs. Some anticancer drugs increase insulin resistance that further reduces their therapeutic effect. ref 
23. It is the fructose in High fructose corn syrup and table sugar that increases BC development and spreading to lungs ref ref
24. Multiple Vitamin use increases DNA repair capacity which decreases breast cancer risk. ref
25. While Multiple Vitamin use increased cancer risk in this study. ref Need to check for differences between locations for other factors to solve this situation.
26. This study showed no real differences between multiple vitamin use and BC, but some differences in a few subsets. ref  Maybe a factor between 23 and 24 above.
27. Women with higher blood levels of carotenoid family have reduced risk for BC. ref  
28. Small studies so far show CoQ10 might restore the death sequence to cancer cells. ref ref
29. RANKL, a ligand necessary to regulate normal and balanced bone rebuilding, is found at increased levels in breast cancer cells. article  ref
30. Chemotherapy drugs and radiation can lead to greater p53 damaged genes. Healthy p53 is activated to stop cancer cell growth, but when mutated does not provide this action. ref  Over 50 percent of cancers including breast cancer exhibit mutations in p53. ref There are natural food elements that prevent p53 damage and restore p53 functions, such as SGS in broccoli. (In other cancers, p53 can be over expressed which also is counter to healthy cells.)
31. The enzyme Aromatase converts androgen to estrogen. It is found at increased levels in breast cancer than in normal breast tissues. Grape seed extract (GSE) contains high levels of procyanidin dimers that are known potent inhibitors of aromatase.
32. A form of vitamin E, alpha tocopherol succinate, exhibits potential to destroy cancer cells and leave normal cells untouched. In fact, it protects the normal cells. ref
33. A form of synthetic vitamin E exhibits far superior action to destroy cancer cells than the natural form as alpha tocopherol. A vitamin E family member, Gamma tocopherol, was also effective and in some cases, even more effective than the synthetic alpha E analogue form. ref 
34. Cancer cells are unable to break apart the synthetic vitamin E analogue to neutralize it's cancer killing potential. Nutritional vitamin E as alpha tocopherol does not exhibit this cancer killing effect, while Gamma tocopherol does in it's natural form. Another reason to use all the family members of vitiamin E instead of just the Government mandated only alpha tocopherol form. A 70 year old vitamin mistake.
35. Women with a BRAC1 or BRAC2 mutation plus higher levels of folates, exhibit a higher risk of BC. ref check out date of this study. Suggests need for more research. Look at this older study. ref 
36. Timing and amounts of dietary folates and supplemental folic acid reveal a U shaped curve for effects. Adverse at under 150mcg /day or over 400mcg/day. Healthy protection in-between, with more prevention before disease and acceleration of disease once established. ref 
37. Over the last 3 years, an intensive research has developed that shows significant BC growth reduction using vitamin A factors all-trans retinoic acid and 9-cis retinoic acid. The results were in the right direction, but not at a desired level. So synthetic derivatives from these two natural vitamin A forms were developed that are reaching 60 to 80% reductions in marker proteins associated with BC spreading ability. ref ref ref 
38. Over the last decade, research has found an association between the gut microbiotia and the risk of breast cancer. ref Harmful bacteria are also foound in the tissues of people with breast cancer versus those without. In the future, brest cancer treatments may include a reinduction of a favorable bacteria mix.
39. Healthy mix of bacteria in the colon also is responsible for the elimination of excess estrogens while unhealthy bacteria strains reasorb estrogens back into the body.                        

***Here is part of conclusion from this referenced study..."vitamin D exerts a biphasic 'dose response' curve on vascular calcification with deleterious consequences not only of vitamin D excess but also of vitamin D deficiency"

The complexity of these facts tends to cloud some issues. Finding a common thread out of these facts, observations, and associations is paramount to developing an effective protocol for treatment and of more importance, prevention. Check this review out, Copied here to prevent loss of link:

"Breast Cancer Res Treat. 2012 Jul 25. [Epub ahead of print] Dietary calcium intake, vitamin D levels, and breast cancer risk: a dose-response analysis of observational studies.

Hong Z, Tian C, Zhang X. Source Kunshan Municipal Center for Disease Control and Prevention, Kunshan, 215300, Jiangsu, People's Republic of China.

Abstract Results from the recent meta-analysis suggested a favorable effect of dietary calcium and vitamin D levels on breast cancer risk. However, the relationship of dietary calcium and vitamin D levels with breast cancer risk is unclear. Thus, the dose-response relationship was assessed by restricted cubic spline model and multivariate random-effect meta-regression. Results suggested that women might suffer from the lowest risk of breast cancer with dietary calcium intake of about habitually around 600 mg/day, dietary vitamin D intake of about 400 IU/day, and serum vitamin D levels of about 30 ng/ml. PMID: 22872547" 

You probably are not amazed that these levels are within the recommendations of the new Vitamin Crieteria.

Then along comes another study showing that the ratio of uncarboxyated osteocalcin to carboxylated has greater influence over the osteocalcin and adiponectin relationship to insulin resistance, blood sugar levels, and energy metabolism than previously thought.  ref

There exists a strong feedback loop between many if not all of these factors to control the energy metabolism and bone control mechanisms with a resulting influence over breast cancer development and promotion. A greater understanding for the systems operating in breast cancers are now known. Vitamins D3 and K2 represent vital links in this protocol. Vitamin D to synthesize osteocalcin production and vitamin K2 to regulate the balance between uncarboxylated and carboxylated osteocalcin since both probably play important roles in the energy metabolic and bone health pathways; insulin secretion and resistance, blood sugar level control of glucose, adiponectin balance, estrogen support, bone turnover with balanced building and tearing down rates. Of course exercise, weight maintenance, and dietary patterns all have significant roles to play as well.

Questions that arise from these facts:

• Why does higher bone density equate with more breast cancers?    There are at least 4 things that can lead to increased bone density:  

1. Genetics for body and bone size and hormone balance (higher estrogen levels strongly implicated in breast cancer rates)   
2. Weight-bearing exercise (Probably not a factor since athletes have lower overall cancer rates, Could be related to oxygenation of tissues preventing cancer development, or increased efficiency of anti-oxidant load balance)   
3. Being overweight stresses bone to become stronger (especially gaining weight as an adult which could be hormone balance related, especially thyroid),(see Note 1 below)    
4. Consuming proper amounts of calcium from foods or supplements and/ or vitamin D as well as fruits and vegetables (some reduced cancers from calcium and D intake, but generally benefits observed with greater intakes of fruits and vegetables).

SIDEBAR: While the extra weight in obese women puts stress on bones similar to exercise and many have higher bone mineral density, another factor also puts them at risk. When the body overall is obese, extra fat enters bones and develops bone marrow fat. This increases the risk for osteoporosis. ref

TAKE AWAY

This discussion is more for general interest to show complexity of theory generation rather than actual use of facts presented. But, the threads presented here might stir awareness of the relatedness of different processes to cancer characteristics. See this article for further discussion. Perhaps, the most important take away is that many nutrients have an optimal window of intake amounts that presents the greatest benefits.

In number 34 above, the retinols are from vitamin A or Beta Carotene sources. Beta carotene comes in at least 4 different forms in nature, all-trans RA, 9-cis RA, 11-cis RA, and 13-cis RA. Synthetic beta carotene in the vast majority of multiple vitamins is only the syntheic all-trans RA form. Eat your vegetables to get all forms, or take a multiple vitamin with algae source beta carotene. Most pre-formed vitamin A in multiples is also synthetic.

Both too low and too high can exhibit adverse reactions. Vitamin D comes to mind here. The latest tendencies are to overcome vitamin D deficiencies by pushing vitamin D levels too high. And look at body weight, higher is protective of bone strength but begins to increase breast cancer risk. Where is the happy medium and balance point? Why is science not rapidly searching for this vital information?

OF INTEREST: A Vitamin Study out of Sweden looking at multiple vitamin use on breast density found an association. Yes, there are certain vitamins that might increase growth of breast tissue or relate to greater breast tissue density. Genetics of course plays the largest part. Folic acid and vitamin C come to mind. Folic acid increases cell turnover rates and vitamin C directs collagen production. Collagen participates in breast tissue density by building connective tissues. While this topic is still exploding with studies and more research results will shortly be surfacing, see this article for more.