Is folic acid disruption the root cause of all cancers?

Insight/Hypothesis: 

There were observations that thyroid hormone supplementation leads to cancer. Does this happen because thyroid hormones may be disrupting folic acid absorption by the body?

Is folic acid disruption the root cause of all cancers?

Thyroid hormones may be disrupting folic acid absorption by the body. Similarly, other hormones like Vitamin D, Vitamin E, Vitamin K - do they deplete folic acid? (May be not, because we know that Vitamin K in ghee, butter is helpful in lot of diseases. Or is it that fat in ghee, butter which is helpful, and not really Vitamin K? Needs more testing.)
Alcohol we know depletes folate levels. Thus it may be leading to cancer.
Smoking may be depleting folate levels.
Viruses and bacteria which cause cancer may causing cancer.

Summary:

Folic acid is crucial for normal DNA synthesis and repair.

Folate deficiency may cause an imbalance in DNA precursors, uracil misincorporation into DNA, and chromosome breakage.

The paper below discusses epidemiological data supporting the involvement of folic acid in the aetiology of cancer.

It also assesses the evidence from cellular, animal and human studies that folic acid can modulate DNA by such mechanisms.

This is perhaps the highest referenced research paper on this subject.

***

Susan J Duthie
Division of Micronutrients and Lipid Metabolism, Rowett Research Institute, Aberdeen, UK

Folic acid deficiency in humans has been linked with megaloblastic anaemia,
neural tube defects in the neonate, and heart disease. Folate has also been
implicated in the development of cancer, especially cancer of the colorectum.
There appear to be two principal mechanisms through which low folate status
may increase the risk of malignancy. Folate deficiency, by reducing intracellular
S-adenosylmethionine (SAM), can alter cytosine methylation in DNA, leading to
inappropriate activation of proto-oncogenes and induction of malignant
transformation. Alternatively, folic acid is crucial for normal DNA synthesis and
repair. Folate deficiency may cause an imbalance in DNA precursors, uracil
misincorporation into DNA, and chromosome breakage. This chapter briefly
describes the epidemiological data supporting the involvement of folic acid in
the aetiology of cancer. It also assesses the evidence from cellular, animal and
human studies that folic acid can modulate DNA by such mechanisms.

Click on the pdf search result in the below google search result

https://www.google.co.in/search?q=Folic+acid+deficiency+and+cancer%3A+mechanisms+of+DNA+instability&rlz=1C1CHBD_enIN781IN781&oq=Folic+acid+deficiency+and+cancer%3A+mechanisms+of+DNA+instability&aqs=chrome..69i57j69i60l2&sourceid=chrome&ie=UTF-8

Alcohol causes cancer (by depleting folate)

Summary:

The below two papers talk about link between alcohol intake and cancer.

The first paper says Alcohol intake tended to be associated inversely with colon cancer, but not with rectal cancer.

The second paper heavy alcohol use and breast cancer has been observed in most studies, even after controlling for known risk factors for breast cancer.

Alcohol has consistently been related to risks of squamous cell carcinomas of the mouth, oral pharynx, larynx, and esophagus in multiple studies of varying design.

My note: From this research paper (http://healthsummary.blogspot.in/2018/01/folic-acid-deficiency-and-cancer.html), we know that heavy alcohol causes folate deficiency. So, perhaps, heavy alcohol drinking must be causing cancers in those with low folate levels.

***


Tohoku J. Exp. Med., 1993, 171, 153-165

A Case-Control Study of Colorectal Cancer
and Its Relation to Diet, Cigarettes, and
Alcohol Consumption in Saitama Prefecture,
Japan

YOSHIHARU HOSHIYAMA, TAKESHI SEKINE * and TAKAFUMI
SASABA

Department of Epidemiology, Saitama Cancer Center
Research Institute, and *Saitama Cancer Center Hospital,
Saitama 362
 HOSHIYAMA, Y., SEKINE, T. and SASABA, T.

A Case-Control Study of
Colorectal Cancer and Its Relation to Diet, Cigarettes, and Alcohol Consumption in
Saitama Prefecture, Japan. Tohoku J. Exp. Med., 1993, 171(2), 153-165 A
case-control study of colorectal cancer in relation to dietary, smoking, and drinking
habits was undertaken in Saitama Prefecture, Japan. The study was based on 181
newly diagnosed cases of adenocarcinoma of the colorectum at a single institution
and 653 general population controls.

Dietary habits were investigated on the
basis of the intake of 12 foods and 12 food groups in a food intake frequency
questionnaire, together with individual food preferences.

Preference for salty
foods was positively related to the risk of both colon and rectal cancer, and the
consumption of seaweed was inversely related to these cancers, both with a
dose-response relation.

Cigarette smoking was inversely related to colon cancer
risk, but not to rectal cancer risk.

Alcohol intake tended to be associated inversely
with colon cancer, but not with rectal cancer.

In the multiple logistic regression,
preference for salty foods (positively) and the consumption of seaweed (inversely)
were independently related to both colon and rectal cancer risks, alcohol;
case-control study; colorectal cancer; diet; smoking.

https://pdfs.semanticscholar.org/6cbc/0388f658aa1201ec299b1eca0ece07f2c962.pdf


***

David B. Thomas
The Fred Hutchinson Cancer Research Center, Seattle, Washington

This is a review of the epidemiologic literature on alcohol and risks of various cancers.

Alcohol has consistently been related to risks of squamous cell carcinomas of the mouth, oral pharynx, larynx, and esophagus in multiple studies of varying design. 

The joint effects of alcohol and smoking are
greater than additive, and are probably multiplicative, suggesting biological synergism. All major types of alcoholic beverages have been causally implicated in the genesis of these diseases. The influence of alcohol on risks of upper aerodigestive tract cancers may be greater in persons with
marginal nutritional status than in better-nourished individuals. Alcohol also has been associated with an increased risk of adenocarcinomas of the esophagus, gastro-esophageal junction, and gastric cardia, but the relationship is not as strong as for squamous cell esophageal carcinomas.

Alcohol
and tobacco account for over 80% of the squamous carcinomas of the mouth, pharynx, larynx, and esophagus in the United States.

Risks of cancers of the distal stomach, pancreas, colon, and rectum have not been consistently related to alcohol, although possible relationships between
beer drinking and rectal cancer and between heavy use of alcohol and pancreatic cancer warrant further study.

Studies of alcohol and liver cancer, in which the confounding influence of hepatitis B was considered, have yielded inconsistent results and should be replicated.

An association between
heavy alcohol use and breast cancer has been observed in most studies, even after controlling for known risk factors for breast cancer, and additional investigations of this issue are warranted. - Environ Health Perspect 103(Suppl 8):153-160 (1995)

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1518951/pdf/envhper00368-0156.pdf

Folic acid deficiency and cancer: mechanisms of DNA instability

Summary:

Folic acid is crucial for normal DNA synthesis and repair.

Folate deficiency may cause an imbalance in DNA precursors, uracil misincorporation into DNA, and chromosome breakage.

The paper below discusses epidemiological data supporting the involvement of folic acid in the aetiology of cancer.

It also assesses the evidence from cellular, animal and human studies that folic acid can modulate DNA by such mechanisms.

This is perhaps the highest referenced research paper on this subject.

***

Susan J Duthie
Division of Micronutrients and Lipid Metabolism, Rowett Research Institute, Aberdeen, UK

Folic acid deficiency in humans has been linked with megaloblastic anaemia,
neural tube defects in the neonate, and heart disease. Folate has also been
implicated in the development of cancer, especially cancer of the colorectum.
There appear to be two principal mechanisms through which low folate status
may increase the risk of malignancy. Folate deficiency, by reducing intracellular
S-adenosylmethionine (SAM), can alter cytosine methylation in DNA, leading to
inappropriate activation of proto-oncogenes and induction of malignant
transformation. Alternatively, folic acid is crucial for normal DNA synthesis and
repair. Folate deficiency may cause an imbalance in DNA precursors, uracil
misincorporation into DNA, and chromosome breakage. This chapter briefly
describes the epidemiological data supporting the involvement of folic acid in
the aetiology of cancer. It also assesses the evidence from cellular, animal and
human studies that folic acid can modulate DNA by such mechanisms.

Click on the pdf search result in the below google search result

https://www.google.co.in/search?q=Folic+acid+deficiency+and+cancer%3A+mechanisms+of+DNA+instability&rlz=1C1CHBD_enIN781IN781&oq=Folic+acid+deficiency+and+cancer%3A+mechanisms+of+DNA+instability&aqs=chrome..69i57j69i60l2&sourceid=chrome&ie=UTF-8

Vitamin B6 and B12 Supplements Appear to Cause Cancer in Men

A newly discovered risk associated with common energy and metabolism pills

JAMES HAMBLIN

AUG 25, 2017   HEALTH

Energy. If you’re not taking vitamin B12, forget about having energy. As The Dr. Oz Show has recommended, “End your energy crisis with Vitamin B12.” The nice thing about sublingual pills is “you don’t need a doctor, you don’t need a prescription.”

And don’t get me started on metabolism. If you want to “supercharge your metabolism and energy levels,” Amazon can deliver you a tall bottle of B12 supplements by the end of the day. Your metabolic processes will be the envy of the neighborhood. (“Is Janice ... on something?” “Yes—B12!”)

These are the sort of vague marketing claims that have propelled the cobalt-based compounds sold as B12 into American hearts and minds and blood in ever-growing quantities. They are extrapolations from the fact that B12 deficiency causes anemia, and correcting that deficiency will alleviate symptoms of fatigue and weakness. But as the National Institutes of Health notes, “Vitamin B12 supplementation appears to have no beneficial effect on performance in the absence of a nutritional deficit.”

Nonetheless around 50 percent of people in the United States take some form of “dietary supplement” product, and among the most common are B vitamins. Worse than just a harmless waste of money, this usage could be actively dangerous. In an issue of the Journal of Clinical Oncology, published this week, researchers reported that taking vitamin B6 and B12 supplements in high doses (like those sold in many stores) appears to triple or almost quadruple some people’s risk of lung cancer.

This is a heavy claim about a very common substance, so it’s worth spending a minute on the methodology. Concerns about B-vitamin supplements and cancer have been percolating for years. They came up quietly in a large trial in Norway that concluded ten years ago. Starting in 1998, researchers assigned 6,837 people with heart disease to take either B vitamins or a placebo.

The researchers then watched as people died and contracted diseases in ensuing years—and the vitamin group raised concerns. In 2009, the researchers reported in the Journal of the American Medical Association that taking high doses of vitamin B12 along with folic acid (technically vitamin B9) was associated with greater risk of cancer and all-cause mortality.

Using more than 55 micrograms daily appeared to quadruple cancer risk.

The largest increase in cancer risk was in the lung. Still, the number of cases of lung cancer among these 6,837 Norwegians was relatively small—so the actual risk was difficult to quantify. But it was big enough to catch the attention of Theodore Brasky and Emily White, two researchers at the Fred Hutchinson Cancer Research Center in Seattle. White had been overseeing a cohort study that involved more than ten times as many people as the Norwegian trial, some 77,000 people across the state of Washington. The cohort is tracking their supplement intake as we speak, and it is also being followed for cancers by the National Cancer Registry.

The Washington study was specifically designed to examine the roles of “dietary supplements”—compounds known as vitamins, minerals, and non-vitamin non-mineral compounds like ginseng—in cancer risk. This was an ideal setup to look at the relationship between B vitamins and cancer, and see if it was indeed worthy of concern. So Brasky and White, along with Chi-Ling Chen at National Taiwan University, broke down this population by B-vitamin use and looked at cancers. Unfortunately their findings were even more significant than the Norwegian trial.

Lung-cancer risk among men who took 20 milligrams of B6 daily for years was twice that of men who didn’t. Among people who smoke, the effect appeared to be synergistic, with B6 usage increasing risk threefold. The risk was even worse among smokers taking B12. Using more than 55 micrograms daily appeared to almost quadruple lung-cancer risk.

There was no apparent risk among women—which is not to say it doesn’t exist, only that it wasn’t apparent.

Why or how would B vitamins increase a person’s risk of cancer?

I asked Brasky what he thought was going on. It’s all hypothetical, and he has no clear idea bout the sex discrepancy. What he does know is that  B vitamins all contribute enzymes and coenzymes to a metabolic pathway that breaks down folate in order to make the bases that comprise DNA. The pathway also regulates the expression of genes (by creating methyl groups that can essentially turn genes on and off). When we have too little of these B vitamins, this pathway can go wrong, leading to problems like incorporation of the wrong types of bases into DNA, which can cause breaks in the strands, and, in theory, lead to cancer.

We’re best to treat vitamins more like pharmaceuticals than like panaceas to be shoveled into us.

Deficiency can also mean genes that should be inhibited are no longer inhibited, also potentially meaning cancer. Sufficiency of certain vitamins is important in cancer prevention, but avoiding excess appears to be similarly important.

Among smokers, who are already exposed to carcinogens, the effect of taking anything that impairs these cellular processes could be even more likely to lead to cancer.

The research team is quick to note that the doses of B vitamins in question are enormous. The U.S. Recommended Dietary Allowance for B6 is 1.7 milligrams per day, and for B12 it’s 2.4 micrograms. The high-risk group in the study was taking around 20 times these amounts.

That could seem nonsensical, except that these are the doses for sale at healthy-seeming places like Whole Foods and GNC. Many sellers offer daily 100-milligram B6 pills. B12 is available in doses of 5,000 micrograms.

I asked Brasky if his finding means that products like these should be more closely regulated—at least to require selling more reasonable doses, or to disclose risks, as is required for pharmaceuticals. Currently, supplements are absolved from this sort of requirement, or even to prove safety or efficacy before going to market. This is dictated by a 1994 law called the Dietary Supplement Health and Education Act (DSHEA).

“The law was created by industry lobbying to keep the FDA away from regulation, so the industry self-regulates,” said Brasky. But he deferred and said he hoped this article wouldn’t be about regulation. “I don’t want to pick a fight with the vitamin industry for any reason.”

So that falls to me. There are legitimate and important uses for B-vitamin supplements, but the emerging evidence suggests we’re best to treat them more like pharmaceuticals than like panaceas to be shoveled into us in pursuit of energy, metabolic fortitude, “cardioprotection,” “bone wellness,” or whatever way in which we’d like to be better.

The enduring theme in health is that more doesn’t mean better. What’s healthy for one person may be unhealthy for another. The fact of a product being sold without a prescription does not mean it is exempt, or that it’s good or even harmless. Any ingested bioactive substance will come with risks and benefits.

The current law gives consumers no reason to expect that risks will be listed on the labels of these products, or that health claims are accurate. A product like a high-dose B6 and B12 supplement hits shelves, and only decades later do researchers begin to understand the long-term health effects, who might benefit from taking it, and who might be harmed.  

https://www.theatlantic.com/amp/article/537654/

 

ABOUT THE AUTHOR

JAMES HAMBLIN, MD, is a senior editor at The Atlantic. He hosts the video series If Our Bodies Could Talk and is the author of a book by the same title. | More

Low white blood cells are a problem with Meat Only Diet - leads to infections

Summary:

1. Meat-only diet eventually leads to low white blood cells (neutrophils).

2. Low white blood cells lead to infections because the protection of white blood cells is not available.

3. Folates are absent in a meat only diet. Low folates leads to low white blood cells.

4. Hence, meat-only diet may be good for a few weeks or couple of months (could depend on individual) for healthy intestine to be fixed. But one needs to restore eating folates to increase white blood cells to fight infections.

***

Source: Even my personal experience with meat-only diet has been similar.

Heather Crimson shared a link to the group: Principia Carnivora.

August 19 at 3:19am · 

I have 4 out of 5 of these. Good thing I'm ZC! 28 months. Still have I issues though with very low white blood cells, so going to see one of Kresser's MD's Monday to hopefully get some decent help for a change! Been trying to get help for 25 years...

5 Reasons You May Need More Protein—Even on a Paleo Diet

Most people naturally eat the right amount of protein for their needs. Protein is such a crucial nutrient that the brain has specific mechanisms that increase your desire for it if you need more an…

CHRISKRESSER.COM

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Esmée La Fleur My white blood cells - neutrophils specifically - bottomed out completely in January. I got sick with a virus 6 times over the winter because of this before I figured out what the problem was. I traced it back to low serum folate. I am taking subcutaneous folic acid injections now and my neutrophils are back up into the healthy range. Not sure why I have this problem while other ZCers do not, but I suspect it is due to malabsorption which is caused by Mast Cell Activation Syndrome in my GI tract. I have not been sick with a virus since I started taking the folic acid injections.

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 · August 19 at 5:55am · Edited