Nutrient Dosage Analysis

Which nutrients or ingredients are worth supplementing?

>For Dosage information go to vitamin Criteria<

The scope here is not to review every nutrient dosage, but the most important ones plus those requested by the membership.

Nutrient Dosages included for:

Amino Acids and proteins, Vitamins, Minerals, Phytonutrients, Probiotic Bacteria and Yeasts, Herbs, Herbal extracts, Enzymes, (still under development)

Evaluation for Dosage criteria:

• Positive (or negative) functions in body
• Scientific research support level 
• Size and scope of potential adverse effects
• Peripheral side effects other than target functions
• Bio-availability of supplement forms
• Absorption percentages
• Purity and quality

Example: Glucosamine    Effective score: 6    Safety score: 5  (out of 10)

1. Forms;  Glucosamine Sulfate, Glucosamine Hydrochloride, & N-acetyl-glucosamine. The Sulfate forms need a salt stabilizer, sodium or potassium chloride.
2. Best form; Doesn't matter. Glucosamine salts are mostly separated during digestion from carrier element anyway.
3. Since the Sulfate form is made from the Glucosamine Hydrochloride form with the addition of a salt stablizer, the Hydrochloride form is a higher concentration and usually a lower price. Early research to improve joint health in dogs used this form.
4. European research was sponsored by the company that patented the sulfate sodium salt form, so most human research available on this form. But since digestion separates, form may not be much of a factor. (It is claimed the sulfur breaks off and forms other compounds with a pH controlling function, but the initial compount structure is stronger and all of it may not break apart)
5. Absorption percentage is represented by % separation in the stomach and resulting ionization process.
6. Absorption for Glucosamine salts is at about 50%+, slightly more for Glucosamine Hydrochloride. 
7. Research sponsored by companies that sell the product tend to be more favorable than later independent results. And that is just what happened with glucosamine.
8. The body naturally builds glucosamine from protein and sugar.
9. Glucosamine is building block for collagen and cartilage, good for joints and all connective tissues.
10. Some studies have showed benefits on joint health. It's worth a try unless....allergies, etc.
11. Glucosamine has shown the ability to reduce STAT3 activity to prevent and maybe stop certain kinds of prostate cancer cell growth  ref   Resveratrol might do this too.
12. These is a question about Glucosamine influencing insulin resistance and blood sugar levels. Some studies show positive and some negative. It appears that research has now found that in uncontrolled or unaware pre-diabetic conditions, glucosamine may have a negative effect. ref  While in controlled cases it might have no effect or a positive one. ref  This needs greater clarification due to the size of the growing diabetic epidemic. While animals studies show negative effects, fortunately, so far human research shows little effect over short term. Longer term studies are needed.  ref
13. DO NOT take Chondroitin, especially if there is any history of prostate problems. Chondroitin may increase the production of versican, a protein that binds to prostate cancer cells and increases cancer spreading. ref (also for breast cancer, ref) ref
14. Dosages. 1000 to 1500 mg.
15. 30% More effective if taken with vitamin C. And with mucopolysaccarides such as green lip mussels or orange footed sea cucumber and curcumin and ginger.
16. DO NOT TAKE CHONDROITIN period. When it is combined with glucosamine, the absorbed amount of glucosamine is reduced. ref
17. Personal note; I get more influence with combination formulas than with glucosamine alone or with chrondroitin, ingredients not used since family history of both prostate and breast cancers.

CAUTION NOTE: Hyaluronic Acid may have this same aspect, especially in breast and prostate cancers. Check out this research on HA levels and oral cancers.  ref   This is very serious since HA is being promoted as a "fountain of youth."  Until these issues are settled: DO NOT TAKE HYALURONIC ACID OR CHONDROITIN. The different molecular size of available products plays a major role in how HA responds in the body. ref  ref   ref

Below From eMedTV.com    

"Are Glucosamine and Chondroitin Safe?

Glucosamine and chondroitin supplements are claimed to provide numerous benefits, but are there any precautions for glucosamine and chondroitin? While the product appears to be safe for most people, you may not be able to take it safely if you have asthma, diabetes, prostate cancer, or high blood pressure. Glucosamine and chondroitin might negatively affect these conditions."

Glucosamine appears the safest ingredient in this group as long as used as suggested. There is a study showing maintainance of joint integrity over 3 month period. ref  Overall joint cartilage information here.

Glutathione         Effective Score: 3*    Safety score: 6

1. A tripeptide protein consisting of cysteine, glutamine, and glycine (amino acids).
2. It forms one of three master cellular detoxification enzymes, Glutathione Peroxidase.
3. One of the most powerful cellular antioxidants with supports for immunity.
4. Glutathione levels are lower in people with heart disease, in Alzheimer's, and some cancers.
5. *Just looking at functions, this nutrient would score a 10, but...
6. *Absorption is very low. There is even some question if it passes into cells intact from the blood stream. One of the leading researchers on glutathione says it probably has to be built in each cell.
7. It has a transport protein that attaches to it in blood and helps move it into the lungs since it is vital to lung function.
8. *Research has found certain nutrients that will increase glutathione production much more than by taking glutathione itself.
9. Vitamin C at 500 mg increased production an average of 50% as long as the building blocks were available. N Acetyl Cysteine and selenium are two of most important ones. 
10. Most important function in cells is to neutralize free radicals developed from energy production in the mitochondria.  

Definition: MItochondria are structures in cells where energy as ATP is produced. As humans age, the number of mitochondria in each cell diminishes and the amount of energy they can produce is reduced. This energy action level of mitochondria is being studied with links to many degenerative diseases. See ingredients CoQ10 and L-Carnitine. 

FOLIC ACID, Trick or Treat

Effective   7(out of 10 for NTD)       Safety   3

Folic Acid is the synthetic form of Folate

First, there are at least 3 issues related to natural folate or synthetic folic acid levels.

• The protecton against NTD developing in the fetus when given to women before pregnancy is well established for folate and folic acid.
• Does folate or folic acid protect and prevent or increase cancer growth rate? both
• How does folate or folic acid (and vitamin B12) influence neurological condtions?  (nerve damage at too low or too high. especially if vitamin B12 low) 
• How does folate or folic acid impact heart disease throught homocysteine control? (reduces homocysteine levels)
• Does folate or folic acid negatively impact immune cell activity? (yes ar both low and excess amounts)

Here are some Facts

Folate is the natural form while Folic Acid is synthetic. Folic Acid is more stable and has much better absorption making it the preferred form for use in supplements and the food fortification program. But, like some synthetics, there are differences from the natural folate form that gain significance with explanation. 

• The synthetic Folic Acid form is not native to the body and does may not perform natural folate functions.
• The Liver has to process the synthetic form and turn it into the natural folate form for activity.
• This Liver process has limits and only can process about 200 mcg of the synthetic form at once, with about 600 mcg over the whole day.
• Consumption over this limit spills unmetabolized folic acid into the blood stream.
• Scientists do not yet know the long term consquences of this situation.
• But what is known is that unmetabolized folic acid in the blood stream suppresses the innate immune system by reducing the activity level of cells called Natural Killer Cells (NK). ref
• NK cells protect against tumor development. ref  
• Folates in the body are hijacked by cancer cells to aid tumor growth.
• Folates protect against DNA damage before cancer, but once cancer is present, folates can help cancers grow faster.

From ScienceDirect, "reduction of NK cell cytotoxicity due to high folic acid intakes may increase the susceptibility to cancer and viral infections especially in the elderly who are already at increased risk for these diseases"

• There is a class of anti-cancer drugs called anti-folates that is designed to stop this hijacking.
• Folic acid and vitamin B12 are involved together in congnitive activites.
• Low Folic acid and low B12 are often associated in dementia as well as megaloblastic anaemia.
• Caution is needed with high folic acid and low vitamin B12, as this anaemia condition can be hidden.

Folate is a valuable nutrient in the body, especially for young women before they become pregnant and during the first trimester to prevent NTD. The important application here is to protect DNA and make sure cells duplicate properly to form a healthy spinal column. Scientists decided to have food manufacturers add synthetic folic acid to wheat and rice flour products to help prevent NTD birth defects. And this worked to reduce this condition. ref ref (<this Canadian study mixes up mg for mcg in flour fortification) ref  But, there appears to be a point where too much folic acid, especially the supplemented synthetic form, creates adverse reactions for some subsets of people, often simply by working too efficiently, or in cases of mutations to the genes involved in folate metabolism. ref For optimum health it is important to stay within the beneficial window of certain amounts, neither too little or too much. Increasing natural food sources of folate is preferred. 

NOTE: It is entirely possible that only natural food sources of folate should be consumed. This leaves out the synthetic folic acid fortified foods that include refined white flour and white rice. If some of these fortified foods are consumed, limits to amount of natural folates as well might be prudent in some situations. This is rather a new development that Science has recently uncovered but hesitates to expose. ref That would mean admitting they missed this aspect in the folic acid food fortification program. ref<large PDF file, you will have to click and download the PDF file, may take some time, BUT easy to read info, especially for colon cancer section 19. (** see below)

The folic acid fortification process in flours and rices, breads and cereals is added at amounts between 115 mcg/100gm to 160 mcg/100 mg. A slice of bread has about 60 mcg. Two slices in a sandwich would add 120 mcg. It is not unusual to have 3-4 servings of grains, breads, pasta, and cereals, and get 240 to 400 mcg per day. Add in a multiple vitmain with 400 to 800 mcg and that is alot of folic acid.

Here is one positive study ref. And another negative study, ref difficult to figure out exact response. And a most excellent review of studies up to 2008.

 Please follow the recommendations established here, especially for women of child-bearing years (16+). Enough red flags are present to demand a limit (or elimination) on the synthetic form, folic acid. ref  ref    ref

Folic Acid on Cancer (stage opposite)

Folic acid most likely does not cause cancer. ref  What it does appear to do, it's job, is to work with DNA and cell division. ref  Since cancer cells grow and divide very rapidly, they appear to hijack folic acid and folates from the body for this faster tumor growth action. This would explain many known observations. ref  ref  ref  ref

PRECAUTION: Numerous studies have now been reviewed together and the results are perhaps slightly mis-leading. The average mortality and/or cancer rates from all the studies shows very little effect overall from folic acid consumption. Just a non significant 6% average increase. What very likely is happening is a dual effect at the same time as explained below.

This next reference pretty much sums it up. Both too low and too high can have adverse effects, while within certain healthy amount limits, normal cell DNA division is protected and cancer is prevented. After a cancer tumor develops, high levels of folic acid may act to promote a faster growth rate. Some types of Cancers have cells with greater numbers of folate receptor docking sites that normal cells. The effect of this is to increase the rate of cell division, simply a normal folate function. There are anti-cancer Drugs that have Anti-folate activity are given to slow cancer growth. ref   ref  ref

A prostate cancer connection is revealed in this study, although just a one person case report, it is pretty dramatic. Notice high B12 was also mentioned since it is often included with folic acid supplement. ref Not all research has found that B12 connection. ref  Prostate cancer is the one that consistently shows a greater adverse connection to higher folic acid amounts. Colon polyp activation may be a close second. Remember, Swedish research from before 2015 should mention that foods are not yet fortified with folic acid and intake levels would be less that in Countries already with folic acid food fortification.

UPDATE 2014:  Check the latest for certain conditions in women exhibiting increased HPV infections and folate concentrations here.

On colon cancer enigma: read this study abstract for possible explanation of benefits/risks. 

Below is another disturbing link for folic acid you should read NOW. It may only be an association, but deserving of further research. Folic acid supplement levels of pregnant women may have lasting effects later in offspring:

Am J Epidemiol. 2009 Dec 15;170(12):1486-93. Epub 2009 Oct 30.

Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study.

Whitrow MJ, Moore VM, Rumbold AR, Davies MJ.

Abstract

This study aimed to investigate the effect of the timing, dose, and source of folate during pregnancy on childhood asthma by using data from an Australian prospective birth cohort study (n = 557) from 1998 to 2005. At 3.5 years and 5.5 years, 490 and 423 mothers and children participated in the study, respectively. Maternal folate intake from diet and supplements was assessed by food frequency questionnaire in early (<16 weeks) and late (30-34 weeks) pregnancy. The primary outcome was physician-diagnosed asthma, obtained by maternal-completed questionnaire. Asthma was reported in 11.6% of children at 3.5 years (n = 57) and in 11.8% of children at 5.5 years (n = 50). Folic acid taken in supplement form in late pregnancy was associated with an increased risk of childhood asthma at 3.5 years (relative risk (RR) = 1.26, 95% confidence interval (CI): 1.08, 1.43) and with persistent asthma (RR = 1.32, 95% CI: 1.03, 1.69). The effect sizes did not change with adjustment for potential confounders. The association was similar at 5.5 years but did not reach statistical significance (RR = 1.17, 95% CI: 0.96, 1.42) in univariable models. These findings on childhood asthma support previous observations that supplementation with folate in pregnancy leads to an allergic asthma phenotype in mice via epigenetic mechanisms and is associated with poorer respiratory outcomes in young children."  More on this connection. ref

SIDEBAR:  A recent report just surfaced that found Women taking Folic Acid just before and during the first 2 months of pregnancy have significantly less autism in their children. ref  This study is from Europe where folic acid is not fortified in foods.

Here is a report on Homocysteine levels in disease and the effects from folic acid consumption along with other B vitamins. Read the section "Is synthetic folate fortification always good for us?."

Folic Acid. Pregnancy, and Breast MIlk

Obviously dietary folate has important roles to play just before pregnancy to safeguard against NTD developing in fetus. Then, after first trimester, a lower level of folic acid might be needed to deal with other future conditions of the fetus. And last, during breast feeding, folic acid might need to be further reduced to prevent unmetabolized folic acid UMFA showing up in blood plama and the possibility of it getting into breast milk. ref  The full consequences of UMFA in breast milk is not fully researched yet. But, with the reduced immune functions, this could have some impact.

DIABETES, HOMOCYSTEINE, and FOLIC ACID

Then, along comes this report on the use of high dose of the three B vitamins thought to be of benefit by lowering homocysteine levels in diabetics. BUT, the results revealed an increase in adverse heart events and a decrease in kidney function. The folic acid amount used in this study was 2,500 mcg. The vitamin B6 at 25Mg and B12 at 1000 mcg should not have been a problem, so most of the adverse effect could be from the folic acid, lowered homocysteine levels, or the combination of the three B vitamins. Interesting! Other studies have not shown a negative result. But, the studies that show a slight positive from folic acid on cardiovascular events are for populations where they DO NOY have grain fortification with folic acid. ref 

Folic Acid Metabolite

What is CALCIUM L-5-METHYLTETRAHYDROFOLATE?  

Copy from Reference best sums up specs:    "New specifications prepared at the 65th JECFA (2005) and published in FNP 52 Add 13 (2005). At the 65th JECFA (2005) the Committee had no safety concerns for the use of the substance in dry crystalline or microencapsulated form as an alternative to folic acid used in dietary supplements, foods for special dietary uses and other foods.

L-5-Methyltetrahydrofolic acid, calcium salt L-Methyltetrahydrofolate, calcium salt L-Methylfolate, calcium L-5-MTHF-Ca

Calcium L-5-methyltetrahydrofolate (L-5-MTHF-Ca) is a synthetic derivative of folic acid, the predominant, naturally occurring form of folate. It is synthesized by reduction of folic acid to tetrahydrofolic acid followed by methylation and diastereoselective crystallization (in water) of L-5-MTHF as its calcium salt. The product contains variable amounts of water of crystallization."  end of copy

Studies show this folic acid metabolite form has more influence lowering Homocysteine levels than taking synthetic folic acid and hoping some of it converts into this natural form by the liver. ref Another study shows that after time, they may be pretty much the same. ref  This gives the metabolism trail of folic acid. While this L-5 form is closer to the natural body folate form, it is not without side effects. Check out this website. And monitor your reactions to see which response you exhibit. Even though adverse effects may be rare, it is wise to be aware.

Wrap UP

One point needs to be addressed. The effects of synthetic form of Folic acid and the natural form folate are to this day quite controversial. The natural folate form is really about 9 different compounds made up of many different elements. The synthetic folic acid form is missing some of these elements which might explain why it has to be converted into the body ready form by the liver. Both deficiency and excess Folic acid intake may exhibit adverse effects in some cases. There is discussion that after tumor development, excess folic acid might increase tumor growth rate as referenced above. This is in contrast to before tumor development, when the excess could be protective and prevent abnormal cell DNA development. Vitamin B12 levels and folic acid both need to be addressed together.  Check out this informative article from Science-Based Medicine.  ref   This is a real eye-opener. Notice that cancers other than just colon may be involved, i.e. breast (tissue density) & prostate. Better outcomes in some cancers were observed when folic acid was deficient (low levels).

In studies looking at supplementing folic acid on dementia, research in Countries without food fortification of folic acid yielded positive results showing less dementia. ref  In Countries with fortification, the results tend to generally be negative showing more dementia in those with extra supplemented folic acid, ref, especially if vitamin B12 is low. The folic acid influence was due to lowering homocysteine blood levels, an element that exhibits a negative effect on dementia.

Folic acid at 400-600 mcg is appropriate for young woman of child-bearing age to prevent NTDs until about 12 weeks into pregnancy, than back off slightly. Not all fortification reports for preventing NTDs were as favorable as has been reported, it depends upon how many servings of folic acid fortified foods are also consumed. >  ref  

OF INTEREST: Here is a report that says folic acid does not increase cancer rate, or at least not significantly. 7.7 % for folic group and 7.3 % for no folic group. ref

Here is a section from this report "In a linked statement, Cornelia M Ulrich, Director of the National Center for Tumor Diseases and German Cancer Research Center, and Joshua W Miller, from Rutgers University in the USA, noted that it is important to remember the dual relationship of folate and cancer. Although it may protect against cancer development, it can also result in the growth of existing cancer cells. This is especially significant, they said, for "those who consume excess folic acid from fortification and supplements combined. Notably, 1-4% of the US population, depending on age, sex, and ethnic origin, exceed the tolerable upper limit (1 mg/day) for total consumption of folic acid." 

Adults should severely limit Folic Acid supplements, PERIOD!  ref  

BUT YOU NEED SOME from either fortified foods which most people consume or from low dose supplements of natural form.

Seniors, if they are not consuming enough natural dietary folates, or consuming fortified foods, might consider taking about 200 mcg. with vitamin B12 to help control Homocysteine levels.

The natural form folate needs to be verified that it does not also have the described synthetic folic acid adverse effects. When articles mention there are no adverse effects from natural folic acid, they are really referring to the fact that you cannot get very much just from natural foods. This does not necessarily imply that natural folates would be safe if consumed in high amounts in supplements that use the natural folate format.

The Homocysteine issue, as well as the whole methylation pathway, and any relationship with heart disease needs to be completely resolved. So far, if it is high, that is not good, but lowering it by taking folic and B12 and B6 does not appear to consistently lower risks. This is a major disappointment for scientists who were sure it would. ref

OF INTEREST: The Methylation reaction is a major area for folic acid. It is this area that sometimes will be the deciding factor as to whether a supplement is going to exhibit a positive or an adverse influence on the body. Methylation is simple the process of adding or removing a methyl group from another element. Adding will start a reaction process while removing the methyl group wil stop a reaction, such as for enzymes. This process is vital in many critical areas of body function: DNA, energy production, neurotransmitters, liver processess, and many others by switching on or off gene expression.

MORE INFO:   Article is copied here to prevent loosing it's website link.

By Steven Reinberg
HealthDay Reporter

TUESDAY, Nov. 17 (HealthDay News) -- Although folic acid fortification of foods can prevent many birth defects, it may also increase the risk for developing cancer, Norwegian researchers report.

Since 1998, many countries have mandated folic acid (vitamin B9) fortification of foods to decrease the incidence of neural-tube defects in newborns. By October 2009, the flour produced in these countries, plus the flour that is fortified voluntarily, represented 30 percent of the world's wheat flour produced in large mills. In addition, some 40 percent of those living in the United States also take dietary supplements containing folic acid, the researchers noted.

However, "Folic acid fortification and supplementation may not necessarily be as safe as previously assumed," said lead researcher Dr. Marta Ebbing, from the Department of Heart Disease at Haukeland University Hospital in Bergen. "Public health and food safety authorities should take this into consideration."

In Norway, foods are not supplemented with folic acid, making it the ideal place to investigate whether or not the supplement increases the risk for cancer, Ebbing noted.

"The study shows that treatment with folic acid for approximately three-and-a-half years was associated with a 21 percent increased risk of cancer and an increased risk of death after six-and-a-half years of follow-up in a large population of patients with heart disease living in Norway, where there is no folic acid fortification of foods," she said.

The report is published in the Nov. 18 issue of the Journal of the American Medical Association.

For the study, Ebbing's team collected data on 6,837 patients with heart disease from two trials. These trials were designed to see if vitamin B could lower homocysteine, a protein associated with an increased risk of heart disease.

In the studies, patients were randomly assigned to receive folic acid plus vitamins B12 and B6, folic acid plus B12, or B6 alone, or a placebo. These trials ran from 1998 to 2005, and were followed through the end of 2007.

The researchers found that patients who received folic acid had a 21 percent increased risk for developing cancer. In addition, of the 341 patients who received folic acid and developed cancer, 136 died -- a 38 percent increased risk compared with patients who did not take folic acid and developed cancer.

The most common cancers associated with folic acid were colorectal, lung, prostate and blood cancer, the researchers noted.

In all, 16.1 percent of the patients who were given folic acid plus vitamin B12 died from any cause, compared with 13.8 percent of patients who received neither folic acid nor vitamin B12, the researchers said.

Bettina F. Drake, an assistant professor of surgery at the Alvin J. Siteman Cancer Center of the Washington University School of Medicine in St. Louis and co-author of an accompanying journal editorial, said that "while the results by Ebbing and colleagues provide some short-term data that is important in helping us understand the complexities in the association between folic acid and cancer risk, this report does not nullify the vast potential long-term benefits that folic acid fortification may have on population health." (preventing birth defects and possibly dementia work coupled with vitamin B12 at moderate levels in seniors.)

Drake noted that the dose of folic acid given to patients in the Norwegian studies was significantly higher (1,000 mcg) than what most people in the United States get. "U.S. fortification appears to have left the population well within safe limits," she said. (unless supplement contains 800 mcg or 400 and one eats 3-4 servings of fortified breads.  1 serving =140 mcg, 3-4 = 420 - 560)

The true effect of folic acid on cancer may take many years of follow-up to determine, Drake said.

Cancer prevention efforts do not start or end with folic acid, Drake added. "Cessation from cigarette smoking for all who currently smoke and prevention of smoking in our youth and adolescents remains the highest priority for cancer prevention," she noted.

"For those who do not smoke, eating a healthy diet and exercising to avoid weight gain or maintain weight loss will translate to lower risk of cancer, diabetes and other chronic conditions," she said. "These are population-wide changes that take time, and the benefits of such lifestylechanges can take years to realize. Sometimes study results do, too."  end of copy

SIDEBAR: Anti-folate drugs are given to slow down cancer growth rate. These drugs hinder the cell division promotion action of folates in the body. Why is this vital bit of information left out of the discussion in the above article? Again, folic acid may not cause cancer, but it sure looks like it speeds up it's growth rate once the cancer has developed. This information fits all the situations described above for both views.

At the proper levels, natural folate in food may be protective against cancer initiation as some early studies observed. The effects of synthetic folic acid may depend upon beginning body level, a benefit against cancers if body stores are low but adverse if body levels are already high, especially if tumors are present. Since Chile initiated fortification of flour in 2001, the colon cancer rate has doubled. This would not mean as much if a similar effect although much smaller also occurred when the United States and Canada introduced fortification. Then there is that 163% increase in prostate cancer rates discovered from the Aspirin and Folic acid study on colon cancer. ref ref ref  Far too many RED FLAGS.

ONE CANCER FOLIC ACID MECHANISM- Immune NK Cell Activity

HOW Folic acid might be involved with increasing cancer risk. Excess Unmetabolized synthetic folic acid spills out into the blood stream if ingested at higher levels than the liver can convert into the natural folate form (260 mcg per meal and about 600 mcg per day). This results in a 22% reduction of the natural killer cell activity, vital to the innate immune system. ref ref  These killer cells are involved in stopping cancer cells so they do not grow into sufficient numbers to build a tumor.   ref    This reference is very important to show how Mother Nature sometimes uses adverse events for beneficial outcomes.  Like the Cyr61 increase from taking NAC with resulting ROS (a free radical) production to prevent Prostate cancer cells from migrating.

**

One last Scientific Report out of Europe from the Reference above copied here due to importance of this complex Folic Acid issue:

The use of folic acid has the benefit of bioavailability, stability and price. However, it is not used without giving rise to some concern. The most prominent concern is that it prevents the timely diagnosis of vitamin B12 deficiency. This issue depends upon the fact that folic acid above a certain level appears in the circulation and enters cells in a way that is not under normal metabolic control. In addition, it directly stimulates DNA biosynthesis and cell division. When this happens in B12 deficiency it masks the emergence of the usual anaemia, allowing the other effect of B12 deficiency, namely neuropathy, to proceed undiagnosed to where it may be irreversible. A more recent concern is that a similar mechanism may be at play in cancer. Thus, while folate/folic acid may prevent the occurrence of new cancers, it may accelerate the growth of pre-existing cancers. These latter concerns are based largely on animal models. More recently observations of apparent increases in colon cancer post fortification in US/Canada have been published. Of greater concern is that recurring polyps in subjects on high dose folic acid were more numerous and had worse pathology than placebo treated peers. Both with respect to masking of anaemia and accelerated cancer growth, greater risk exists in the face of increasing levels of unmetabolised folic acid is in the circulation. Such folic acid does not arise at low intakes but the body’s ability to convert it to natural folate is easily saturated by moderate levels of intake.

Update on Saturday, December 10, 2022 at 8:47AM by Team RightWay

To add support to the above article on Folic Acid, copied next are results from a 5 year review study of research published in 2018. These results highlight the significance of proper vitamin usage, dosages, forms, and synergistic combinations for Folic Acid on cancer risk. 

Folate and Its Impact on Cancer Risk

Renee Pieroth 1, Stephanie Paver 2, Sharon Day 3, Carolyn Lammersfeld 4

Affiliations expand

• PMID: 30099693
 
• PMCID: PMC6132377
 
• DOI: 10.1007/s13668-018-0237-y

Abstract

Purpose of review: Research has evaluated the potential impact of folate on cancer risk with conflicting findings. Studies have demonstrated increased risk, no effect, and decreased risk. This review summarizes findings of mixed results between folate intake, serum levels, gene polymorphisms, and cancer risk based on meta-analyses from the past five years.

Recent finding: Low or deficient folate status is associated with increased risk of many cancers. Folic acid supplementation and higher serum levels are associated with increased risk of prostate cancer. Gene polymorphisms may impact risk in certain ethnic groups. Folate has been studied extensively due to its role in methylation and nucleotide synthesis. Further prospective studies are needed to clarify optimal levels for nutrient remediation and risk reduction in those at risk, as well as elucidate the association between high intake, high serum levels, and prostate cancer risk. 

THIS IS ANOTHER VERY VITAL PIECE OF THE SUPPLEMENT PUZZLE.

Hyaluronic Acid

EFFECTIVE SCORE:  7          SAFETY SCORE: 3 (OUT OF 10)

Another trick or treat ingredient. Hyaluronic acid is involved in moisture retention, such as for limiting skin wrinkles and for joint lubication. The treat is to get Hyaluronic acid (HA) to help maintain cartilage and prevent joint pain without any side effects. The trick is that while both large and small HA molecules may prevent tissue damage especially in joints, the small HA molecules also feeds tumor growth simply due to their natural method of action. Thus, both the large and the very tiny size molecules have positive actions, while the small to medium size molecules should be avoided. ref Supplements of Hyaluronic acid come in many different size molecular weights. Click on the following reference for good info, BUT note they also sell HA ref

Here is the bottom line: High molecular weight hyaluronic acid (HMW-HA) is a regulator, found in vessel walls and joints to maintain integrity and control against inflammation.  ref ref <injections When there is tissue injury, especially around joints, body wisdom breaks off a part of this HMW-HA forming a small size fragment of hyaluronic acid called LMW-HA, low molecular weight, and sends it to the injury site to begin the healing process. LMW-HA adds moisture, creating swelling or inflammation, and also increases blood flow by building new blood vessels to bring needed nutrients. ref  These actions limit joint movement to speed up healing, especially for skin wounds. Eventually, as healing progresses, HMW-HA increases while LMW-HA decreases until the site is back to normal. A problem arises at cancer tumor sites where these small LMW-HA are found in abundance. It could be that the body looks at the tumor as an injury and sends out lots of LMW-HA to attempt to heal the tissue. But instead, the function of LMW-HA to increase blood flow by building new blood vessels unfortunately aids the growth of tumors. It has now been discovered that some cancer cells increase the production of an enzyme that works on the large size HA to break it down into smaller size molecules. ref Plus, people naturally produce different amounts of this enzyme, HYAL1-S, and its counter enzyme that blocks this tumor promotion action, called HYAL1-AS. Both HYAL1-S and HYAL1-AS influence the way HA functions. Doctors measure these enzyme levels to help determine who is at greater risk for relapse after cancer treatment. It was discovered that some cancer cells probably have the ability to increase HYAL1-S production. Prostate cancers are influenced more than breast cancers. ref  Both low HYAL1-S and extremely high might not be desirable. ref  ref

CAUTION:  The different molecular weights of HA can be influenced by various related enzymes that degrade HA and generate secondary forms. DIFFERENT CANCER CELLS MAY OR MAY NOT HAVE THE SAME NUMBER OF RECEPTORS FOR HA which could completely REVERSE the roles of the different molecular weight HA elements. This unique aspect allows scientists to use the size of HA that attracts to each cancer type as a chemo-drug targeting vehicle.** This takes advantage of different cancer enzyme profiles. BUT, AS A SUPPLEMENT, Hyaluronic Acid MAY NOT BE WISE SINCE AT MANY DIFFERENT SIZES, IT HAS OPPOSING EFFECTS. ref 

ABSORPTION OF HA

The vitamin industry discovered that the first supplements of HMW-HA exhibited a very low absorption rate. So they found a way to increase absorption by creating supplements of smaller molecules, LMW-HA. This was possibly before the complete picture of how LMW-HA functions in the body was known. There are still questions on absorption of HA, especially the HMW size. It most likely breaks down with limited absorption. Many studies and medical applications use injectible HA. And YES, the smaller size may indeed feed tumors, ref and inflammation. ref  This reference also mentions how antioxidants prevent fragmentation. Smaller size HA is related to increased scar tissue formation. More research is needed to verify the exact processes that occur in humans and if LMW-HA taken orally gets into the bloodstream intact or is broken apart during digestion, plus how enzyme levels modify actions.

SCIENTIFIC PROOF FOR LMW-HA AT TUMOR SITES

Cancer cells placed in a test tube with LMW-HA show greater growth rates. When an enzyme to breakdown the LMW-HA is added (PEP-1 in next reference), the cancer cell growth rate declines.  ref

SIDEBAR: What science does know is that since LMW-HA goes to tumor sites, in the nanoparticle size, it has proven to be a good combining agent with cancer drugs to get the drugs to just target tumors and leave healthy tissues alone. HA has the ability to increase the building of certain anticancer drug induced structures and helps keep these elements in solution. ref ref   But, next, the slightly larger HA molecules soon formed a non-penetrating shield that blocked chemo-drugs from getting to and killing cancer cells.  

NOTE: Some Nutritionists take the view from early research that HA does not cause cancer (correct but may contribute) and might actually help protect against it. And that HA is found at cancer sites because it it attempting to heal (correct again). But the way it tries to heal, creating inflammation and building new blood vessels, is exactly why it is problematic. HA's other functions also participate in cancer cell migration, proliferation, and adhesion, all devious cancer cell ploys to grow faster and spread. The direction HA contributes to cancer development, growth, and spreading may depend upon the relationship between the 3 enzymes (HAS-1, -2, -3) that influence HA production and activity. ref

Cancer cells might also send out enzymes to further breakdown more HMW-HA to continue using the bodies own protective mechanisms against itself. And this is exactly the POINT, large molecular weight HA is (usually) protective while the smaller low molecular weight fragments (potentially) create inflammation and other nasty actions at cancer sites. This is also seen with folic acid, and a few other nutrients.  

Again, a balance point must be found where HA protects and heals without promoting undo inflammatory stress and tumor growth. There are two different applications here to consider. First is tissue repair at injury sites. The next is chronic inflammation from damaged joints. At just the right levels and molecular size, HA controls both the creation of healing inflammation at injury sites and also limits this action so it does not get out of control. Plus, measuring the different production levels of the related HA enzymes gives Scientists an idea of the progression rate for in cancer types.

ON LIVER AND HA: Serum Hyaluronate is measured to indicate level of inflammation in liver fibrosis condition instead of using the more invasive liver biopsy. Liver fibrosis is associated with liver diseases. For people with impaired livers, consuming hyaluronic acid may be problematic.

ARTERIES AND HA: Inflammation is also a major player in artery health. ref HA and size of molecules is a concern for atherosclerosis plaque stability as well as for cancers. The size of HA and related enzymes that impact production and size of HA structures is simply not to messed with until Science determines exact actions in health and disease.

HOW TO SUPPLEMENT 

Since it is still in question as to how large the molecular weight of HA needs to be to not stimulate tumor promotion, or what determines the type of HA enzyme that is action dominate, the prudent supplement approach for Hyaluronic acid is NOT TO USE at this time. Look for ways to get the body to build its own HMW-HA.

The following research section is copied here to explain why HA should not be used without proper knowledge and correct forms:

"Extra-cellular matrix (ECM) is closely correlated with tumor progression. Hyaluronic acid (HA) is a component of the ECM, it is an unsulfated anionic linear glycosaminoglycan polymer comprised of a repeating glucuronic acid and N-acetylglucosamine disaccharide motif [1]. HA keeps tissues hydrated, maintains osmotic balance and cartilage integrity [2]–[3]. HA also actively regulates cell adhesion, migration, and proliferation by interacting with specific cell surface receptors such as CD44 and RHAMM [4]. The concentration of HA is elevated in several inflammatory diseases and various carcinomas, including bladder, prostate, breast, lung, colon, and so forth [5]–[10]. Small fragments of HA, generated by Hyaluronidase (HAase), stimulate angiogenesis [11], [12]. In tumor tissues, it may promote tumor growth and metastasis probably by actively supporting tumor cell migration and offering protection against immune surveillance [13]."  ref

Can you see why this nutrient needs caution for its use? Many Protective functions, but look what happens when there is runaway inflammation at cancer sites, at artery wall lesions, or in liver disease. ref  It is just the way this nutrient functions that gets it into trouble. There may still be mitigating elements waiting to be discovered that control HA actions as to direction, such as the enzyme mix and any other gene variations. More research is vitally needed.

IF YOU WANT THE BENEFITS OF HA, there are some Brands with higher molecular weight HA. Size would have to be over 300,000 daltrons, preferable over 500,000 or more. Researchers usually have to inject HMW-HA to bypass limited digestive absorption. While larger size limits absorption, the consequences of small fragments may not be worth the price. And there is always the unwelcome possibility that HA breaks down during digestion. Plus, add the effect of different enzyme conditions and the only safe usage of HA is the precautionary one of not to use unless under Medical supervision. Maybe short periods of consumption might be OK but not chronic usage. Remember, many disease conditions are present many years before they are manifested to an observable result.

What helps the natural body production of HMW-HA? It is known that Vitamin C increases collagen production. But what about glycosaminoglycans, the building blocks of HA. Collagen and HA levels naturally reduce with age. This reference shows that Vitamin C did increase glycosaminoglycan amounts. And there might be ways to slow the breakdown of HA, but balance is vital as 1/3 of the 15 grams in the average body are broken down and built back up every day. Information on protecting cartilage here.

Another study showing positive Vitamin C effects on collagen production. Comparing fast cell rates from young babies to the slow producing cells in Elders, Vitamin C made the old cells produce faster with increased densities of collagen. This is of vital importance.

IS HYALURONIC SAFE TO TAKE?

While WEBMD says probably safe, there are far to many situations where it might be contra-indicated and have an acceleration effect on some disease conditions. Best to support body wisdom for production and distribution of HA and let nature determine size and amounts to produce. Remember, HA appears to increase inflammation when the body needs it for healing at an injury site, but this condition becomes adverse if it continues chronic and long term, situations that LMW-HA supplementation might enhance.

**Since Hyaluronic acid in nanoparticle size has the ability to target and penetrate certain types of cancer cells, it is being used by Scientists as a vehicle to combine with and deliver chemotherapeutic drugs into those cancer cells. This is beyond any nutritional or health aspect relating to HA action. The nanoparticle size is only 6-10 disaccharides. Large HA molecules might contain 500,000. Most small LMW-HA supplements contain 50,000 to 250,000.

Vitamin C controversy

Vitamin C use against the common cold was started by Linus Pauling research. But, this area is extremely controversial even to this day. A large amount of biased research muddies the topic. ref

Vitamin C has some family members that increase vitamin  C activity as well as protect vitamin C against oxidation. Citrus Bioflavonoids, hesperidin, and rutin. They largely help with capillary fragility. Vitamin C in necessary for collagen production. Plus, flavonoids have unique functions other than the ones of vitamin C. ref 

Check out the following two research sduty results to see why Vitamin C is controversial.

First Reference says in diabetic women, vitamin C increases Cardiovascular Disease.

Next Reference says high dose vitamin C reduces Cardiovascular Disease.

        Which one is correct?  Maybe both?

Here is a Reference four years later that supports the second reduced risk. The evidence appears to be building for a reduced risk except maybe in diabetics?  Note that plasma vitamin C levels were obtained mostly from fruit and vegetable intake, although vitamin C level showed a greater reduction in risk of CVD than consumption of fruits and vegetables. One possible action is for reducing inflammatory marker C-Reactive Protein. ref   Plus this Vitamin C research on increasing Glutathione levels impacting immune system. ref

FACT: Athletics taking vitamin C exhibit as much as a 50% reduction of common colds. Athletes after extreme exercise experience a lowered immunity and are more susceptible to cold viruses, especially during winter exposure. This vitamin C level of effect was not found in non-active people. article

VITAMIN C ON EXERCISE 

Now it appears a full circle has occurred. Back to vitamin C and E having a negative effect on exercise induced positive insulin sensitivity. Remember that diabetes begins from reduced insulin sensitivity. Exercise helps prevent unless you take vitamins C and E when you exercise. reference Very Interesting! This aspect was covered before. 

Bottom line goes back to the fact that the body needs a balance between anti-oxidants and pro-oxidation aspects. The body has adapted to use some pro-oxidants for beneficial functions before anti-oxidants step in and neutralize them.  ref

NOTE: Here is another study showing high dose Vitamin C reduces the positive benefits of exercise on muscle endurance. The 1000 mg dose evidently was too much and destroyed some free radicals before the body could use them for positive functions.

VITAMIN C on IMMUNITY  ref

Copy from above study reference conclusion: "Overall, vitamin C appears to exert a multitude of beneficial effects on cellular functions of both the innate and adaptive immune system. Although vitamin C is a potent antioxidant protecting the body against endogenous and exogenous oxidative challenges, it is likely that its action as a cofactor for numerous biosynthetic and gene regulatory enzymes plays a key role in its immune-modulating effects. Vitamin C stimulates neutrophil migration to the site of infection, enhances phagocytosis and oxidant generation, and microbial killing. At the same time, it protects host tissue from excessive damage by enhancing neutrophil apoptosis and clearance by macrophages, and decreasing neutrophil necrosis and NETosis. Thus, it is apparent that vitamin C is necessary for the immune system to mount and sustain an adequate response against pathogens, whilst avoiding excessive damage to the host." Another ref

VITAMIN C on GLYCATION

Vitamin C and it's effects on the glycation process  ref  ref  need to be added into this discussion. Does Vitamin C act as a pro-oxidant in diabetics as the first reference above suggests? In this capacity it would increase glycation and speed artery disease, an effect observed in diabetes. There could be other factors that determine which way vitamin C goes on this issue. ref <What is Alc ref  Is it possible that since vitamin C is made from glucose in most mammals, it is still close to the same molecule and reacts with proteins just like glucose? OR, it might just be that higher vitamin C levels are associated with higher glucose levels, an associated factor for diabetes. 

This last ref is an in-depth look at the research with analytical intent. The vast majority of research shows vitamin C acts an anti-oxidant. The few reports of C as a pro-oxidant are in test tube studies with the addition of an ion metal such as copper acting to oxidize LDL cholesterol. This unique set of circumstances needed for this probably almost never occurs in the body. One has to say almost or rarely since some flukes have been found to happen, like vitamin E changing from an anti-oxidant into a pro-oxidant from the effects of an element in cigarette smoke leading to increased lung cancer.

For a good reference on vitamin C with research summaries. Note this is a Government site and is very cautious about some of the newly discovered vitamin C actions. All things technologically Vitamin C here.

Vitamin C, Flavonoids, and Cancers (this will need another article)

This topic is still undergoing research. Here are some of the facts. Vitamin C has two transporters, SVCT1 and SVCT2. the transporter vitamin C connects with determines where in the body it will go. ref  The next reference talks about these two vitamin C transporters on skin sun damage protection. ref

Natural versus Synthetic Vitamin C

This topic generates quite a bit of controversy. First, here is what is known. Natural vitamin C as made in an orange has the same elements as ascorbic acid processed in the lab usually from corn sugar. But, there are two different isomers that may develop, L-ascorbic and D-ascorbic. An isomer is a slightly different arrangement of the same elements. in the orange, vitamin C is all in the L-form. Synthetic Vitamin C is also produced in the L-ascorbic form. The D-form can be made in the Lab and is used in foods as a preservative. It is not active in the body as vitamin C activity except for the antioxidant one.

Some animal studies show differences between the two, but so far, human studies have not found the differences observed in those animal studies. It might be that the differences are difficult to observe or that in the body, the differences are not significant. Because most animals make their own vitamin C, only a few are available for vitamin C studies. This area needs more research. But, what is known, is that vitamin C benefits from the inclusion of bioflavonoids. Bioflavonoid exhibit a protective effect on vitamin C as well as have benefits of their own.

This is an area of continuing research.

DOSAGES on EXCRETION AMOUNTS

At 100 mg per day, there is no vitamin C found in urine. Over 100 mg there is 25%. At 200 mg, the percentage doubles to 50%. Plus, at 200 to 250 mg. vitamin C reaches a peak of blood levels that is not increased until dosages reach 2,500 mg. This does not necessarily mean the extra is not working before it is excreted. At one gram per day there is a peak reached for tissue, plasma and blood levels. But over 250 mg, urine excretion rapidly increases and absorption decreases. Extra vitamin C could still increase somewhat in other tissues and organs. Mostly a factor of longer time in body not higher levels ref 

At 3 grams of vitamin C per day, the body reaches the top excretion percentage amount. There is now unmetabolized vitamin C found in urine. Plus, there is also the development of an enzyme system to destroy the extra vitamin C in the body. ref  A rebound effect must be at play if one abruptly stops taking large amounts. ref This enzyme is still produced for awhile which lowers the dietary vitamin C levels below pre-study amounts. This rebound negative action lasts for about 10-12 days.

Update on Thursday, November 6, 2014 at 10:20PM by Team RightWay

Vitamin C has Heart

Check out this scientific abstract copied here to preserve. It shows vitamin C has a positive effect on radicals such as HIF-1. BUT, to get enough in heart, the secondary form ascorbic acid turns into is used, dehydroascorbic acid, or DHA (not the fish oil). "We found that adult rat cardiomyocytes accumulate vitamin C by transporting dehydroascorbic acid (DHA), the oxidized form of vitamin C, but do not transport ascorbic acid. Loading cells with vitamin C by DHA treatment resulted in resistance to hypoxia- and hypoxia/reoxygenation-induced cell death associated with the quenching of reactive oxygen species."  

Doesn't this sound like a positive effect for vitamin C? Check out this result> ref

Free Radic Biol Med. 2004 Nov 1;37(9):1419-29.

Update on Thursday, November 6, 2014 at 10:34PM by Team RightWay

Nature of Vitamin C Regeneration

Nature dealt humans a mean low blow when she took away the ability of the human body to make it's own Vitamin C. Here is one way humans have survived so long without this ability that most other mammals process.

"Although there exists a sodium-dependent transporter for vitamin C, it is present mainly in specialized cells, whereas the glucose transporters, the most notable being GLUT1, transport Vitamin C (in its oxidized form, DHA)^[2] in most cells, where recycling back to ascorbate generates the necessary enzyme cofactor and intracellular antioxidant, (see Transport to mitochondria)."  from Wikipedia

Alpha Lipoic regenerates used vitamin C back into a functioning form. So vitamin C can be used again and again. Here is an excellent article to describe how Vitamin C recycles.

This concept reveals a rather large piece of the health puzzle. It shows that even though a long time ago humans lost the enzyme necessary to build vitamin C in the body, nature developed a way to compensate and let humans survive on only the vitamin C coming in with food. Vitamin C is a vital health factor by generating collagen, the major protein in connective tissue that holds many body parts together and allows skin and arteries to stretch. And the impact of glutathione enzymes on Vitamin C regeneration is also a factor to consider which allows the body to reuse vitamin C over and over again. Vitamin C also increases glutathione blood levels to continue this repeating cycle. ref

Quiet Vitamin K

Vitamin K mostly flies under the radar. Very few health studies are conducted relative to other vitamins, but this does not mean vitamin K is any less vital. New information is now available to vault Vitamin K to mega-star status.

WHY SO LOW KEY 

Perhaps it is due to the fact that the major known function for Vitamin K was for blood coagulation, and that was pretty cut and dried. Vitamin K is supplied in the diet by many food sources, especially the greens. Doctors measure vitamin K's blood clotting ability before surgery, plus also in connection with blood thinners in treating cardiovascular disease to prevent spontaneous clotting. Plus all newborn babies have been receiving vitamin K injections to prevent internal bleeding conditions since many infants measure low in vitamin K. Most Nutritionists before this discovery thought vitamin K levels were not an issue because these was enough in diet plus the intestinal bacteria also produced some as well. Funny, since many infants are born low, shouldn't this have sounded alarms that the Mothers were vitamin K deficient during pregnancy? Since 1944, all babies have been given a vitamin K injection on the first day of life to prevent internal bleeding conditions. 

SIDEBAR: As margarine use grew popular, a new form of vitamin K emerged from the Hydrogenation of oils used to make margarine. ref This new vitamin K form, dihydrophylloquinone, is less active than the normal form of K1, phylloquinone, and could even interfere with the normal form causing a further deficiency of vitamin K actions. ref ref Look for both partially-hydrogenated on food ingredient labels and also the trans-fat content. But, remember, if a serving is under .5 grams, the trans-fat content is listed as 0. Many food manufacturers such as for some Girl Scout cookies keep the level just under .5 gram per serving. While this is a very small amount and is listed as "0" on labels, look at the label for the above trans fat forms listed, it all adds up. About trans-fat.

The body simply maintains the critical blood clotting ability mechanism at functioning amounts until vitamin K levels get extremely low. Amazing! Now with further research, vitamin K functions have expanded beyond blood clotting but the Public remains in the dark about this new work. Areas now include artery and vein integrity, bone building, cancer cell destruction, and insulin resistance. Pretty impressive!  

For many years, bone Doctors have been measuring the amount of activated (carboxylated) osteocalcin in the blood as a way to measure the body's bone building activity. Osteocalcin (OC) can be in two forms, activated (cOC) or non-activated (unOC). Only the activated form functions to bind calcium into bone. Vitamin D directs the building of osteocalcin, BUT it is vitamin K that activates it (carboxylation). Doctors never mentioned this blood test really indicated vitamin K levels. Can you see why most bone building studies testing just calcium and vitamin D would be doomed to failure with if vitamin K(2) levels were too low?

Extra INTEREST:  Osteocalcin levels are not only needed for bone building, but new research points to a direct link to blood sugar control through beta cell and insulin production and sensitivities. article ref Exercise and vitamin D increase Osteocalcin. Thus, it is of vital importance to get the right amount of vitamin K2 to maintain the balance between carboxylated and un-carboxylated osteocalcin since they both appear to have different functions and not only bone building, blood sugar levels, and lately added brain development. It is interesting to note that Medical Doctors have been measuring for the amount of carboxylated osteocalcin as a marker of bone building activity. BUT, they never told patients it was really a vitamin K2 test. The blood sugar control link is relatively young research. ref 

VITAL: Both forms of osteocalcin are vital for important body functions. Since Vitamin K2 participates in the regulation between these forms, it is critical to not over or under dose. This appears in many other vitamins as well, not enough as well as too much can both have adverse effects. Science should be searching for the appropriate window of amount needed, but so far, no recommendation. 

FORMS OF VITAMIN K

Vitamin K comes in many forms, with 3 main forms: K1, as phylloquinone from green leafy plants is the dominiate form; K2 has ten forms as different menaquinones (MK-4, Mk-7, Mk-9, etc) from grass fed organ meats, dairy, and fermented foods such as cheese and soy. MK-4 and MK-7 is also produced synthetically so get products that list natto as natural source for Mk-7, MK-4 is always synthetic, as well as K3, which is synthetic and toxic and only used in animal feed, thus not used in nutrition and only under close inspection for certain cancers, where it's toxic function is exploited. See reference below. Vitamin K2 as MK comes in at least 10 forms. For humans, MK4 is the most common form found in the body. Another form is MK7 from fermented soy as Natto now available as a supplement, but it is also available as a synthetic, so make sure natto is listed as source. Hard cheeses provide mainly MK-8 and MK-9.

Vitamin K2 can be made from K1 by bacteria in the gut and by another unknown process also occurring or beginning in the intestinal tract during absorption. It is questionable how much of the bacteria driven form becomes available to the body since it quickly is eliminated out with stools. MK-4 is the only form built in body tissues from K1. One very important aspect to these different forms is how long they last in the body. K1 lasts about 8 hours; K2 as MK4, about 4 hours; and K2 as MK7 over 2 days. You will see supplements of much greater dosages (1000mcg) for synthetic Vitamin K2 as MK4 at very low prices, but since it is rapidly cleared out of the system, K2 as MK7 at 50-100 mcg might really be the more valuable option as the smaller dosages will build up over 3 days. ref   This might be the reason some vitamin Brands put out supplements containing all 3 forms of vitamin K.

Dosages of VITAMIN K

The AI for Adequate Intake in the USA is set at 90 mcg/day for females and 120 mcg/day for males. This is measured as K1 since K2 is difficult to access. K1 intake averages slightly less for elders and in Alzheimer's disease. The conversion of K1 in the body also most likely decreases with age as well. Remember K1 is converted in certain body tissues into K2 as MK-4 in the brain, pancreas, and other glands. This might become a factor in maintaining health. 

VITAMIN K other Health Functions

CANCER

The cancer connection is amazing. Certain forms of vitamin K are under consideration as cancer treatments. Here is one connection with prostate cancer. ref  (be sure to read about the other cancers in this reference with a vitamin K connection)  Vitamin K2 appears more active than Vitamin K1 for these functions. The level of body conversion of K1 into the K2 form is still in question. And finally, check out the date of this research about vitamin K2 and breast cancer cell lines. ref (It is interesting that the toxic form of vitamin K3, not used as a nutritional supplement, is used to kill cancer cells since cell death from the toxic activities of the K3 form prove valuable in this situation.)

VITAL CAUTION: This is very new. It appears total OC regulates normal prostate cell growth. The OC form ucOC limits prostate cancer cell growth while the cOC form stimulates prostate cancer cell growth. Finding a balance point is vital now. ref

The above issue points to an enigma. The body needs cOC for bone health, but too much and prostate cancer cells gain a growth advantage. Since vitamin K2 generates cOC, it may not wise to supplement in prostate cancers until more information surfaces to clarify. 

BONE

One aspect of vitamin K(2) and bone health regards the fact that in many studies even though the calcium group built more bone density, the vitamin K group usually had fewer fractures. Interesting! Ask a Nutritionist to explain this. Bone strength is not just from density alone, but also structure of bones, how bones are built, plus structure coupled with density. This is an important reference for the many vital functions of K, especially K2. This reference adds greater insight, vitamin K2 probably works to keep bones stronger, often without any significant change in bone density. Low density bones can be strong if they have better sturcture, less porosity, or holes in bone.

HEART

Vitamin K also activates another protein, Matrix GLA, in the artery wall to prohibit the bonding of calcium into the artery walls. The amount of calcium that calcifies in artery walls is directly related to the risk of Cardiovascular Disease. ref ref  Here is a newer study published 2015> ref

CAUTION: Like so many nutrients, vitamin K might have a narrow window where the most benefits are found. At least it appears to not have toxic effects so the only considerations are for over activity. Since the 3 vitamin K forms last different length of times in the body, a unique amount has to be found for each one to arrive at the optimal amount. IT IS CRITICAL for SCIENCE TO QUICKLY FIGURE OUT THESE IDEAL AMOUNTS since they are not exactly known and there is an interaction between two of the forms in the body to further complicate things. Important blog info on K2 from a Cardiologist.

BRAIN

Extending the work of vitamin K on artery health protection, this process also helps limit calcium build up participating in brain lesions, indicated in dementia. Dr Payne is leading research into brain lesions. She has found that higher amounts of both calcium and vitamin D play negative roles for increased brain lesions.

DOSAGE INFO

(This is for Vitamin K2 as MK4, usually synthetic with a very short life in body.) A study found that in kidney patients, 100 mg. of vitamin K2 increased over baseline the amount of carboxylated Osteocalcin 17%, 200 mg. increased 33%, and 300 by 46%. Unfortunately, have to pay to access study for baseline level. Another study showed 125 mg over 4 weeks increased levels by 77% while 300 mg increased 94%. Different ways to measure. Thus, 50-100 mg. could be a prudent amount to supplement until levels are tested. The 100 mg amount could be used to build levels for about 2 weeks, and then back off to one every third day. The 45 mg size could be used daily, with 2 skip days per week. Remember, there most likely is a balance point needed between the two forms of osteocalcin, unO and cO, for all the many functions of osteocalcin. Bone mineralization, blood sugar control, prostate cell growth, artery calcification inhibition, and most likely many others waiting to be discovered.

Vitamin K2 as MK7 from fermentated foods like cheeses and soy natto, is only given in microgram sizes, a very small amount as it lasts many days in the body instead of only a few hours like MK4, which is why it is given in amounts 1000 times larger, the milligrams.

WRAP UP

Since Vitamin K participates in many vital health areas, blood coagulation, bone growth, blood sugar control, cardiovascular artery health, brain legions, as well as in some cancer protection, it is critical to know how much to take and which forms. The cancer fighting effect of vitamin K2, mitochondrial membrane disruption, may be inhibited by higher amounts of vitamin E as alpha tocopherol. The bone and blood sugar mechanisms are related to the ratio of carboxylated osteocalcin to uncarboxylated osteocalcin. Vitamin K regulates carboxylation. See the potential dilemma? Luckily, this blood sugar control problem of vitamin K has only been observed in animal studies and not in human studies so far.

Part of the reason both K1 and K2 should be measured and the greatest beneficial levels discovered is due to how each is circulated in the body. This may also be why K2 forms are better for certain sideline functions of vitamin K beyond blood coagulation. Vitamin K1 as phylloquinone is mostly found in the liver and blood stream bound to TRL, Tryglceride-rich Lipoproteins. The MK forms of vitamin K2 not only bind with TRL but also with LDL and HDL which give them greater exposure to arteries and other body tissues like bones, brain, and numerous glands.

CAUTION:    

Update on Wednesday, November 19, 2014 at 10:16AM by Team RightWay

Follow Up to Quiet Vitamin K

From Medscape at Large comes a Doctor's views on Vitamin K2. Concise, simple, and to the point. This deserves to be shared:

"Hello and welcome. I am Dr George Lundberg, and this is At Large at Medscape.

I do not know anything about nutrition as it relates to chronic illness, including obesity. I used to think that was because, probably like you, I was taught so little about nutrition in medical school. I have spent a medical lifetime reading articles about nutrition, before and after publication. But I am still woefully ignorant of "nutritional truth."

Take vitamin D. The minimum daily requirement prevents rickets. But then, just a few years ago, it became popular to check vitamin D blood levels. And many people were found to have "low" vitamin D levels. Then many diseases were found to be associated with "vitamin D deficiency," except it turns out that many labs were not doing the tests in equivalent ways.

After a whole lot of fuss and study, the Agency for Healthcare Research and Quality (AHRQ) issued a report this year that finds no consistent correlation between vitamin D and health outcomes such as cardiovascular disease, all-cause mortality, several types of cancer, or bone health.^[1] Amazing.

Which Brings Us to Vitamin K

What do you know about vitamin K? It has something to do with blood coagulation, right? Yes, but that is vitamin K₁. I am asking about vitamin K₂. I bet you have not thought much about that vitamin.

Here are nine things every physician should know about vitamin K₂:

1. It exists.

2. It is essential for life and health.

3. There is currently no reliable blood test to measure it.

4. Your body makes a certain amount via menaquinone-4 (M-4) in your gut from vitamin K₁.

5. That may not be enough.

6. Your body probably needs more vitamin K₂ for disease prevention than it manufactures, so nutritional sources are important.

7. Foods rich in vitamin K₂ (often in the form of M-4 or M-7) include: natto (fermented soybeans); green, leafy vegetables; organ meats such as goose liver; grass-fed beef; dairy; eggs; and fish.

8. Or you can take nutritional supplements to achieve healthy levels of vitamin K₂.

9. Deficiencies of vitamin K₂ are now being reported in serious journals to be associated with—get this—all-cause mortality, cardiovascular disease, osteoporosis, diabetes, many forms of cancer, dementia, and chronic inflammation. ref

Sound familiar?

Is vitamin K₂ the ubiquitous disease-associated vitamin D-like deficiency, sans blood testing, all over again? A fad disease about to pop up, flourish, and disappear? Or is this a real, late-to-the-table, fundamental new understanding of possible causes of many common diseases, disability, and death? And if vitamin K₂ is taken correctly, will it result in prevention and treatment of same? Look it up; check it out.

I do not know how this is going to work out, but I have a hunch that vitamin K₂ will turn out to be a really big deal rather than only "the new vitamin D," with much fuss and little substance.

Most of this research is being done in Japan and Europe, especially The Netherlands, well away from the US Department of Agriculture and lobbyists for the American food industry and its captured government and academic partners.

I owe my current interest in this topic to a product of the Internet as the world's greatest library—a well-educated, nonscientist who got really interested in this topic and will not let up. Thank you, Micki Jacobs of Cincinnati.

That's my opinion. I am Dr George Lundberg, at large at Medscape." - end of copy

NOTE: Since some of the Vitamin D and K activities are linked, both vitamins have to be measured for any research to be valid, especially for bone studies. It is rather ironic that Doctors have for so long measured Carboxylated Osteocalcin vs Uc levels as an indicator for the amount of bone building but never said the test really was measuring vitamin K activity. Then add sun avoidance to limit vitamin D production plus margarine trans-fats interfering  with vitamin K effectiveness, and this may be a perfect storm to explain some modern day disease patterns.