MTHFR mutations

shijing

The Living Force
Note: I've split this from the Endothelial Dysfunction thread since it seems to deserve its own.

I want to give an update since I just had another cardio appointment yesterday and got my bloodwork results back. As it turns out, my cardiologist requested a series of genetic tests for both clotting factor and something called MTHFR. The clotting mutations were negative, but I did test positive for heterozygous MTHFR mutations at the C677T and A1298C locations:

http://mthfr.net/mthfr-c677t-mutation-basic-protocol/2012/02/24/

http://mthfr.net/mthfr-a1298c-mutation-some-information-on-a1298c-mthfr-mutations/2011/11/30/

Since two locations are involved, it puts me in the category of "compound heterozygous", which is significant since the mutations work together synergistically. I've only started researching it, but my understanding at present is that this derails my methylation and BH4 pathways. Part of what's involved is an inefficiency in converting folic acid into methylfolate and 5HTP (or its precursor L-Tryptophan) into serotonin; the combination of these mutations is implicated in cardiovascular disease as well as a number of other autoimmune and degenerative disorders.

This makes sense out of several things in hindsight -- I'm betting that I've inherited this from my dad (who suffers from several things on the list including fibromyalgia, cardiovascular disease and Parkinson's), and have probably passed it on to my daughter. My mom responds normally to both 5HTP and L-Tryptophan, but they have never seemed to have an effect on either me, my dad or my daughter, which would make sense if they're not getting converted into serotonin (or at least not converted efficiently). I'm having my daughter tested the week after next, and have alerted my extended family on my dad's side about my results in case any of them want to get tested as well. This may also explain why I've experienced some ongoing symptoms such as fatigue and anxiety despite doing my best to adhere to the diet and use various supplements.

My doctor's analysis and recommendations are below -- I'm highlighting problematic (from our point of view) areas in blue:

Risk factors: endothelial dysfunction, positive MTHFR, elevated cholesterol (because of increased risk of oxidation), elevated levels of uric acid, smoking, high protein diet

Nutritional recommendations:
[list type=decimal]
[*]Adhering to an anti-inflammatory diet -- the Mediterranean diet (high in vegetables and some fruits, fish, small amounts of organic/free-range chicken and meat, use of olive oil and quality fats (nuts and seeds, avocado, coconut oil), very little amounts of sugars and simple carbs.
[*]Maintain hydration for detoxification -- water intake goal is 1/2 of body weight in ounces (avoid caffeine).
[/list]

Supplement recommendations:
[list type=decimal]
[*]Multivitamin (with 5-MTHF)
[*]Digestive enzyme
[*]Fish oil
[*]Medibulk fiber
[*]Probiotic
[*]CoQ10
[*]L-Arginine
[*]Magnesium
[/list]

Lifestyle recommendations:
[list type=decimal]
[*]Eliminate all smoking of tobacco (directly impairs endothelial function)
[*]Exercise (both cardio and resistance)
[*]Test saliva pH first thing each morning and urine pH on second morning sample
[*]Daily stress reduction (meditation, yoga, biofeedback, breathing exercises)
[/list]

I'm also supposed to retest my endothelial function in 6 months to evaluate my progress. In general, I'm happy about this in the sense that it seems to explain a lot of health issues that have plagued both me and my family members, and gives me a direction to work in actually doing something about them. The sticking points in the treatment plan above (that I've highlighted) revolve around smoking, plant consumption, and the whole pH issue which seems like it's probably bogus. One thing that seems contradictory is that I'm supposed to avoid folic acid, but the green leafy vegetables I'm supposed to eat more of are some of the highest sources of folic acid (they're being included in the above plan for their antioxidants (good) as well as to supposedly bring down my pH (probably irrelevant)).
 

LQB

The Living Force
FOTCM Member
Re: Re: Endothelial dysfunction

Shijing said:
My doctor's analysis and recommendations are below -- I'm highlighting problematic (from our point of view) areas in blue:

I don't think the keto diet (as we refer to it) is high protein - protein should be restricted.

Looks like there is a bazillion methylation support protocols out there - this blog post might help a bit: http://cfsmethylation.blogspot.com/2012/04/bumbling-around-methylation.html

On top of this, many of us have genetic variants that slow down some of the methylation enzymes or cause us to use up B 12 or B5 or methyl groups too quickly. In either case, we may find ourselves needing much larger amounts than we could ever get from food.

Even if you don’t have ME-CFS or another neuro-endocrine illness, be advised that methylation is now believed to be a key factor in preventing heart disease and cancer. It’s an important factor in endometriosis, a healthy pregnancy, and many female syndromes that involve estrogen imbalances as well as mental disorders like schizophrenia, anxiety disorder, and depression.

This doesn’t make methylation support a panacea for everything that ails you, but since methylation is a process that all cells in the body use to move CH2 radicals from one molecule to another, which supports over 40 different processes in the body ranging from the management of stress hormones, to immune reactions, to estrogen metabolism, to antioxidant control, a glitch in one place is bound to create a jam in another.

Apparently there are a number of doc/researchers that believe that any chronic inflammation must be controlled first before the methylation paths are supplemented - thus the emphasis on stress.

In a recent WAPF article (http://www.westonaprice.org/cancer/cancer-to-the-rescue), Stephanie Seneff suggests the importance of sulfate in the body (and its transport) in relation to cancer. She suggests that an unacknowledged benefit of epsom salts is the sulfate (as opposed to the Mg), and that curcumin/turmeric are good sulfate transporters (besides anti-inflammatory/anti-oxidant). She doesn't mention methylation but there may be a connection considering how many pathways are involved.

Hope this helps a bit ...
 

RedFox

The Living Force
FOTCM Member
Re: Re: Endothelial dysfunction

Hi Shijing, thanks for posting this as I hadn't connected it to Endothelial dysfunction before.
I did a genetic test at the end of last year and got my results back in January. I have a similar mutation 677CT/1298CA - 2 heterozygous mutations (compound heterozygous) gs192.

_http://www.snpedia.com/index.php/Gs192
You have a combination of 2 SNP variations in MTHFR which influence homocysteine levels. This is found in ~20% of people. 0.08% of people had a double copy of a mutation in one of the SNPs, and a single mutation in the other. [PMID 15834246] . gs193 indicates double mutations in both snps, and people with this are believed to be critically impacted. Note that both snps have minus orientation.
rs1801131 is at position 1298
rs1801133 is at position 677
_http://www.mthfrheds.com/
_https://www.23andme.com/you/community/thread/5312/
_https://www.23andme.com/you/community/thread/2001/
_http://www.youtube.com/watch?v=ZA8GUIRqIkE

MTHFR mutation frequencies in a sample of 37,000 individuals:
677CT/1298AA 22.8% - 1 heterozygous mutation
677CC/1298CA 20.8% - 1 heterozygous mutation
677CT/1298CA 19.8% - 2 heterozygous mutations (compound heterozygous) gs192
677CC/1298AA 15.3% - no mutations
677TT/1298AA 12.2% - 1 homozygous mutation
677CC/1298CC 08.8% - 1 homozygous mutation
677TT/1298CA 00.05% - 1 heterozygous and 1 homozygous mutation gs192
677CT/1298CC 00.03% - 1 heterozygous and 1 homozygous mutation gs192
677TT/1298CC none - 2 homozygous mutations (compound homozygous) gs193

Some of the terminology took me a little while to get my head round, specifically 677T is shorthand for 677TT and 1298C is shorthand for 1298CC (if I understand it correctly) which would homozygous mutations which are the most serious, not heterozygous (CT/CA etc) which are less serious but still can make things sluggish/problematic.
I mention this because it should help you take an objective step back in the research. I've found you have to be very careful in reading exactly what they are saying in relation to which specific mutation(s) is being discussed.

Some things I've picked up along the way. Choline seems to be very important, specifically the body may be converting it to betaine/trimethylglycine (TMG) for the secondary methyfolate pathway. As such you can end up depleted of choline (unless you are eating a lot of egg yolks/fish).
Supplementing with TMG helped balance things out (the theory is it helps lower homocysteine levels and has helped with my ability to tolerate stress), but once it did my body doesn't seem to need much of it any more.
Supplementing with phosphatidylcholine can be very useful to start with too.
08D3B238-46BF-40B8-BD56-C13300141480.jpg


On the food sources of choline you have to watch for things that block the absorption of thiamine (egg whites, certain types of fish) as this is also important to endothelial function. Getting enough thiamine is also important. Benfotiamine (an active form of thiamine) can be very beneficial (it removes Advanced Glycation End Products from the body, especially the circulatory system) but you have to watch for blood pressure drops if you are sensitive/taking too much.

Anti-thiamin factors (ATF)

The presence of anti-thiamin factors (ATF) in foods also contributes to the risk of thiamin deficiency. Certain plants contain ATF, which react with thiamin to form an oxidized, inactive product. Consuming large amounts of tea and coffee (including decaffeinated), as well as chewing tea leaves and betel nuts, have been associated with thiamin depletion in humans due to the presence of ATF (26, 27). ATF include mycotoxins (molds) and thiaminases that break down thiamin in food. Individuals who habitually eat certain raw, fresh-water fish; raw shellfish; and ferns are at higher risk of thiamin deficiency because these foods contain thiaminase that normally is inactivated by heat in cooking (1). In Nigeria, an acute neurologic syndrome (seasonal ataxia) has been associated with thiamin deficiency precipitated by a thiaminase in African silkworms, a traditional, high-protein food for some Nigerians (28).

[..]In a randomized, double-blind pilot study, high-dose thiamin supplements (300 mg/day) were given for six weeks to hyperglycemic individuals (either glucose intolerant or newly diagnosed with type 2 diabetes). Thiamin supplementation prevented any further increase in fasting glucose and insulin levels compared with placebo treatment but did not reduce the hyperglycemia (36). However, one study suggested that thiamin supplementation might improve fasting glucose levels in type 2 diabetics in early stages of the disease (i.e., pre-diabetes or early diabetes) (37).

Chronic hyperglycemia in individuals with diabetes mellitus contributes to the pathogenesis of micro-vascular diseases. Diabetes-related vascular damage can affect the heart (cardiomyopathy), kidneys (nephropathy), retina (retinopathy), and peripheral nervous system (neuropathy). In diabetic subjects, hyperglycemia alters the function of bone marrow-derived endothelial progenitor cells (EPC) that are critical for the growth of blood vessels (38). Interestingly, a higher daily intake of thiamin from the diet was correlated with more circulating EPC and with better vascular endothelial health in 88 individuals with type 2 diabetes (39). An inverse association has also been found between plasma concentrations of thiamin in diabetic patients and the presence of soluble vascular adhesion molecule-1 (sVCAM-1), a marker of vascular dysfunction (32, 40). Early markers of diabetic nephropathy include the presence of serum albumin in the urine, known as microalbuminuria. Administration of thiamin or benfotiamine (a thiamin derivative) prevented the development of renal complications in chemically-induced diabetic rats (41). A randomized, double-blind study conducted in 40 type 2 diabetic patients with microalbuminuria found that high-dose thiamin supplementation (300 mg/day) decreased excretion of urinary albumin compared to placebo over a three-month period (40). Since thiamin treatment has shown promising results in cultured cells and animal models (42-44), the effects of thiamin and its derivatives on vascular complications should be examined in diabetic patients.

I'd suggest exploring a high dose highly available (i.e. not generic) B vitamin supplement too, as a general starting point - i.e. the active form of all the B vitamins.

Bromelain, serrapeptase and nattokinase are useful for clearing up any potential blockages in the circulatory system (both from plaque and blood clots) - so far these have been most helpful for me, but I'm missing something is seems as they can make things worse too. My conclusion is I'm missing whatever is causing the vascular damage (and plaque/clotting as a result), so this is dealing more with a symptoms than the cause.

Having said all that, do check the protocols available as supplementing in isolation can throw other systems out of balance. *edit to add* one Very important thing noted in the protocols I've read is adequate potassium intake, the requirements of which may go up a lot as things start to work properly (especially when supplementing sublingual forms of B12).

Just reducing homocysteine level may or may not help vascular health (the research is mixed), so it appears to be only part of the problem (years of high homocysteine have probably unbalanced other system/resources). Elevated levels do seem to be good indicators of vascular disease though.

A mix/overview of this research can be found here (it appears to ignore genetic factors) _http://www.raysahelian.com/homocysteine.html
[..]
How to reduce high homocysteine level
Adequate intake of folic acid, B6, and B12 will assure that the blood homocysteine level is kept under control. Considering the possibility that there may be individuals, especially the elderly, who are deficient in B6, folic acid, and B12, an inexpensive and simple way to decrease the rate of damage to the brain from a high homocysteine level would be by supplementing with these vitamins. Keep dosages low.

Danger to the Brain?
In addition to potentially contributing to cardiovascular conditions, homocysteine may be detrimental to the brain since it can act as a toxin to brain cells. Dr. L. Parnetti and colleagues, from Perugia University in Italy published an article discussing its role in cognitive decline. They say, "Homocysteine may represent a metabolic link in the cause of atherosclerotic vascular diseases and old-age dementias. An excessive amount is an independent risk factor for coronary artery disease, peripheral vascular disease, and cerebrovascular disease. Homocysteine is a reliable marker of vitamin B12 deficiency, a common condition in the elderly, which is known to induce neurological deficits including cognitive impairment. A high prevalence of folate deficiency has been reported in geriatric patients suffering from depression and dementia. Both these vitamins occupy a key position in the remethylation and synthesis of S-adenosylmethionine (SAM-e), a major methyl donor in the central nervous system. Therefore, deficiencies in either of these vitamins leads to a decrease in SAM-e and an increase in homocysteine, which can be critical in the aging brain."
Nutritionists at Tufts University in Boston have also found a connection between B vitamins, homocysteine, and memory. They investigated the relations between blood concentrations of homocysteine and vitamins B-12, B-6 and folate, and scores from a battery of cognitive tests for seventy male subjects, aged 54-81 years. Lower concentrations of vitamin B-12 and folate and higher concentrations of homocysteine were associated with poorer memory. Furthermore, people with low levels of vitamin B12 or folic acid may have a higher risk of developing Alzheimer's disease.
In older people, higher blood levels of homocysteine are associated with lower mental functioning.
homocysteine, an amino acid that has been tied to heart disease and stroke, can be lowered with folate and vitamins B6 and B12. The latest finding suggests to researchers that B vitamin supplements may help prevent homocysteine related cognitive decline.

S-adenosylhomocysteine, a better test for vascular disease than homocysteine?
Some studies indicate higher blood concentration of S-Adenosylhomocysteine appears to be a more sensitive indicator of vascular disease.

Phosphatidylcholine
A report in the 2005 issue of the American Journal of Clinical Nutrition, indicates that a high daily dose of choline, supplemented as phosphatidylcholine, lowers fasting as well as postmethionine-loading plasma homocysteine concentrations in healthy men with mildly elevated concentrations. If high homocysteine concentrations indeed cause cardiovascular disease, choline intake may reduce cardiovascular disease risk in humans.

Liver health
High homocysteine level is also associated with higher ALT levels when liver enzyme levels are checked.

Memory loss
A population-based, prospective study of elderly British individuals shows that risk of memory loss increases over time with increasing levels of total blood homocysteine and decreasing folate levels. Homocysteine is an amino acid in the blood. Too much of it ups the risk for coronary heart disease, stroke and fatty deposits in peripheral arteries. High circulating levels of homocysteine, especially with advancing age, have also been associated with cognitive impairment. Homocysteine levels in the blood are strongly influenced by diet and genetics. Folic acid and other B vitamins help break down homocysteine in the body. Annals of Neurology 2005.

Osteoporosis
Women who have high levels of the amino acid homocysteine in the blood are at increased risk for low bone mineral density (BMD). Using data from a population-based cohort of more than 5,300 middle-aged and elderly men and women, researchers observed that total homocysteine level was inversely related to hip BMD among middle-aged and elderly women, but not among men. Women with high levels were nearly two times more likely to have low BMD compared with women with low levels. Moreover, high homocysteine predicted osteoporosis among women after adjusting for confounding factors such as smoking, physical activity, intake of vitamin D and calcium, and use of estrogen.

[..]

_http://atvb.ahajournals.org/content/17/10/2074.long
Homocysteine as a Risk Factor for Vascular Disease

Enhanced Collagen Production and Accumulation by Smooth Muscle Cells

Alana Majors,
L. Allen Ehrhart,
Ewa H. Pezacka

Abstract

Abstract An increased plasma homocysteine level is an independent risk factor for vascular disease. However, the pathological mechanisms by which homocysteine promotes atherosclerosis are not yet clearly defined. Arterial smooth muscle cells cultured in the presence of homocysteine grew to a higher density and produced and accumulated collagen at levels significantly above control values. Homocysteine concentrations as low as 50 μmol/L significantly increased both cell density and collagen production. Cell density increased by as much as 43% in homocysteine-treated cultures. Homocysteine increased collagen production in a dose-dependent manner. Smooth muscle cells treated with homocysteine at concentrations observed in patients with hyperhomocysteinemia had collagen synthesis rates as high as 214% of control values. Likewise, collagen accumulation in the cell layer was nearly doubled in homocysteine-treated cultures. Addition of aquacobalamin to homocysteine-treated cultures controlled the increase in smooth muscle cell proliferation and collagen production. These results indicate a cellular mechanism for the atherogenicity of homocysteine and provide insight into a potential preventive treatment.

So the bromelain, serrapeptase and nattokinase may be helpful again here - as long as homocysteine levels are controlled and thiamine/choline levels are adequate.

Well that's the overview of some of the research I've done, I'll see if I can post more relevant stuff later.
 

RedFox

The Living Force
FOTCM Member
Re: Re: Endothelial dysfunction

This is a good starting point/background reference.


https://youtu.be/j0XSygnJuxI

I found a group that appear to have been doing some pretty good research (they suggest paleo and are dealing with people who are on paleo but still have health problems like CFS/fybromialga/hormonal imbalances etc).
Their protocol over can be found here (I've yet to try it).
_http://forums.phoenixrising.me/index.php?threads/active-b12-protocol-basics.10138/

Finally (for a wider scope on the MTHFR problem) Doctor Amy seems to have done some excellent research.
_http://www.dramyyasko.com/our-unique-approach/methylation-cycle/

This is pretty much where I'm upto in my research.
 

SMM

The Living Force
Re: Re: Endothelial dysfunction

RedFox said:
Hi Shijing, thanks for posting this as I hadn't connected it to Endothelial dysfunction before.
I did a genetic test at the end of last year and got my results back in January. I have a similar mutation 677CT/1298CA - 2 heterozygous mutations (compound heterozygous) gs192.

_http://www.snpedia.com/index.php/Gs192
You have a combination of 2 SNP variations in MTHFR which influence homocysteine levels. This is found in ~20% of people. 0.08% of people had a double copy of a mutation in one of the SNPs, and a single mutation in the other. [PMID 15834246] . gs193 indicates double mutations in both snps, and people with this are believed to be critically impacted. Note that both snps have minus orientation.
rs1801131 is at position 1298
rs1801133 is at position 677
_http://www.mthfrheds.com/
_https://www.23andme.com/you/community/thread/5312/
_https://www.23andme.com/you/community/thread/2001/
_http://www.youtube.com/watch?v=ZA8GUIRqIkE

MTHFR mutation frequencies in a sample of 37,000 individuals:
677CT/1298AA 22.8% - 1 heterozygous mutation
677CC/1298CA 20.8% - 1 heterozygous mutation
677CT/1298CA 19.8% - 2 heterozygous mutations (compound heterozygous) gs192
677CC/1298AA 15.3% - no mutations
677TT/1298AA 12.2% - 1 homozygous mutation
677CC/1298CC 08.8% - 1 homozygous mutation
677TT/1298CA 00.05% - 1 heterozygous and 1 homozygous mutation gs192
677CT/1298CC 00.03% - 1 heterozygous and 1 homozygous mutation gs192
677TT/1298CC none - 2 homozygous mutations (compound homozygous) gs193

Some of the terminology took me a little while to get my head round, specifically 677T is shorthand for 677TT and 1298C is shorthand for 1298CC (if I understand it correctly) which would homozygous mutations which are the most serious, not heterozygous (CT/CA etc) which are less serious but still can make things sluggish/problematic.
I mention this because it should help you take an objective step back in the research. I've found you have to be very careful in reading exactly what they are saying in relation to which specific mutation(s) is being discussed.

Some things I've picked up along the way. Choline seems to be very important, specifically the body may be converting it to betaine/trimethylglycine (TMG) for the secondary methyfolate pathway. As such you can end up depleted of choline (unless you are eating a lot of egg yolks/fish).
Supplementing with TMG helped balance things out (the theory is it helps lower homocysteine levels and has helped with my ability to tolerate stress), but once it did my body doesn't seem to need much of it any more.
Supplementing with phosphatidylcholine can be very useful to start with too.
08D3B238-46BF-40B8-BD56-C13300141480.jpg


On the food sources of choline you have to watch for things that block the absorption of thiamine (egg whites, certain types of fish) as this is also important to endothelial function. Getting enough thiamine is also important. Benfotiamine (an active form of thiamine) can be very beneficial (it removes Advanced Glycation End Products from the body, especially the circulatory system) but you have to watch for blood pressure drops if you are sensitive/taking too much.

Anti-thiamin factors (ATF)

The presence of anti-thiamin factors (ATF) in foods also contributes to the risk of thiamin deficiency. Certain plants contain ATF, which react with thiamin to form an oxidized, inactive product. Consuming large amounts of tea and coffee (including decaffeinated), as well as chewing tea leaves and betel nuts, have been associated with thiamin depletion in humans due to the presence of ATF (26, 27). ATF include mycotoxins (molds) and thiaminases that break down thiamin in food. Individuals who habitually eat certain raw, fresh-water fish; raw shellfish; and ferns are at higher risk of thiamin deficiency because these foods contain thiaminase that normally is inactivated by heat in cooking (1). In Nigeria, an acute neurologic syndrome (seasonal ataxia) has been associated with thiamin deficiency precipitated by a thiaminase in African silkworms, a traditional, high-protein food for some Nigerians (28).

[..]In a randomized, double-blind pilot study, high-dose thiamin supplements (300 mg/day) were given for six weeks to hyperglycemic individuals (either glucose intolerant or newly diagnosed with type 2 diabetes). Thiamin supplementation prevented any further increase in fasting glucose and insulin levels compared with placebo treatment but did not reduce the hyperglycemia (36). However, one study suggested that thiamin supplementation might improve fasting glucose levels in type 2 diabetics in early stages of the disease (i.e., pre-diabetes or early diabetes) (37).

Chronic hyperglycemia in individuals with diabetes mellitus contributes to the pathogenesis of micro-vascular diseases. Diabetes-related vascular damage can affect the heart (cardiomyopathy), kidneys (nephropathy), retina (retinopathy), and peripheral nervous system (neuropathy). In diabetic subjects, hyperglycemia alters the function of bone marrow-derived endothelial progenitor cells (EPC) that are critical for the growth of blood vessels (38). Interestingly, a higher daily intake of thiamin from the diet was correlated with more circulating EPC and with better vascular endothelial health in 88 individuals with type 2 diabetes (39). An inverse association has also been found between plasma concentrations of thiamin in diabetic patients and the presence of soluble vascular adhesion molecule-1 (sVCAM-1), a marker of vascular dysfunction (32, 40). Early markers of diabetic nephropathy include the presence of serum albumin in the urine, known as microalbuminuria. Administration of thiamin or benfotiamine (a thiamin derivative) prevented the development of renal complications in chemically-induced diabetic rats (41). A randomized, double-blind study conducted in 40 type 2 diabetic patients with microalbuminuria found that high-dose thiamin supplementation (300 mg/day) decreased excretion of urinary albumin compared to placebo over a three-month period (40). Since thiamin treatment has shown promising results in cultured cells and animal models (42-44), the effects of thiamin and its derivatives on vascular complications should be examined in diabetic patients.

I'd suggest exploring a high dose highly available (i.e. not generic) B vitamin supplement too, as a general starting point - i.e. the active form of all the B vitamins.

Bromelain, serrapeptase and nattokinase are useful for clearing up any potential blockages in the circulatory system (both from plaque and blood clots) - so far these have been most helpful for me, but I'm missing something is seems as they can make things worse too. My conclusion is I'm missing whatever is causing the vascular damage (and plaque/clotting as a result), so this is dealing more with a symptoms than the cause.

Having said all that, do check the protocols available as supplementing in isolation can throw other systems out of balance. *edit to add* one Very important thing noted in the protocols I've read is adequate potassium intake, the requirements of which may go up a lot as things start to work properly (especially when supplementing sublingual forms of B12).

Just reducing homocysteine level may or may not help vascular health (the research is mixed), so it appears to be only part of the problem (years of high homocysteine have probably unbalanced other system/resources). Elevated levels do seem to be good indicators of vascular disease though.

A mix/overview of this research can be found here (it appears to ignore genetic factors) _http://www.raysahelian.com/homocysteine.html
[..]
How to reduce high homocysteine level
Adequate intake of folic acid, B6, and B12 will assure that the blood homocysteine level is kept under control. Considering the possibility that there may be individuals, especially the elderly, who are deficient in B6, folic acid, and B12, an inexpensive and simple way to decrease the rate of damage to the brain from a high homocysteine level would be by supplementing with these vitamins. Keep dosages low.

Danger to the Brain?
In addition to potentially contributing to cardiovascular conditions, homocysteine may be detrimental to the brain since it can act as a toxin to brain cells. Dr. L. Parnetti and colleagues, from Perugia University in Italy published an article discussing its role in cognitive decline. They say, "Homocysteine may represent a metabolic link in the cause of atherosclerotic vascular diseases and old-age dementias. An excessive amount is an independent risk factor for coronary artery disease, peripheral vascular disease, and cerebrovascular disease. Homocysteine is a reliable marker of vitamin B12 deficiency, a common condition in the elderly, which is known to induce neurological deficits including cognitive impairment. A high prevalence of folate deficiency has been reported in geriatric patients suffering from depression and dementia. Both these vitamins occupy a key position in the remethylation and synthesis of S-adenosylmethionine (SAM-e), a major methyl donor in the central nervous system. Therefore, deficiencies in either of these vitamins leads to a decrease in SAM-e and an increase in homocysteine, which can be critical in the aging brain."
Nutritionists at Tufts University in Boston have also found a connection between B vitamins, homocysteine, and memory. They investigated the relations between blood concentrations of homocysteine and vitamins B-12, B-6 and folate, and scores from a battery of cognitive tests for seventy male subjects, aged 54-81 years. Lower concentrations of vitamin B-12 and folate and higher concentrations of homocysteine were associated with poorer memory. Furthermore, people with low levels of vitamin B12 or folic acid may have a higher risk of developing Alzheimer's disease.
In older people, higher blood levels of homocysteine are associated with lower mental functioning.
homocysteine, an amino acid that has been tied to heart disease and stroke, can be lowered with folate and vitamins B6 and B12. The latest finding suggests to researchers that B vitamin supplements may help prevent homocysteine related cognitive decline.

S-adenosylhomocysteine, a better test for vascular disease than homocysteine?
Some studies indicate higher blood concentration of S-Adenosylhomocysteine appears to be a more sensitive indicator of vascular disease.

Phosphatidylcholine
A report in the 2005 issue of the American Journal of Clinical Nutrition, indicates that a high daily dose of choline, supplemented as phosphatidylcholine, lowers fasting as well as postmethionine-loading plasma homocysteine concentrations in healthy men with mildly elevated concentrations. If high homocysteine concentrations indeed cause cardiovascular disease, choline intake may reduce cardiovascular disease risk in humans.

Liver health
High homocysteine level is also associated with higher ALT levels when liver enzyme levels are checked.

Memory loss
A population-based, prospective study of elderly British individuals shows that risk of memory loss increases over time with increasing levels of total blood homocysteine and decreasing folate levels. Homocysteine is an amino acid in the blood. Too much of it ups the risk for coronary heart disease, stroke and fatty deposits in peripheral arteries. High circulating levels of homocysteine, especially with advancing age, have also been associated with cognitive impairment. Homocysteine levels in the blood are strongly influenced by diet and genetics. Folic acid and other B vitamins help break down homocysteine in the body. Annals of Neurology 2005.

Osteoporosis
Women who have high levels of the amino acid homocysteine in the blood are at increased risk for low bone mineral density (BMD). Using data from a population-based cohort of more than 5,300 middle-aged and elderly men and women, researchers observed that total homocysteine level was inversely related to hip BMD among middle-aged and elderly women, but not among men. Women with high levels were nearly two times more likely to have low BMD compared with women with low levels. Moreover, high homocysteine predicted osteoporosis among women after adjusting for confounding factors such as smoking, physical activity, intake of vitamin D and calcium, and use of estrogen.

[..]

_http://atvb.ahajournals.org/content/17/10/2074.long
Homocysteine as a Risk Factor for Vascular Disease

Enhanced Collagen Production and Accumulation by Smooth Muscle Cells

Alana Majors,
L. Allen Ehrhart,
Ewa H. Pezacka

Abstract

Abstract An increased plasma homocysteine level is an independent risk factor for vascular disease. However, the pathological mechanisms by which homocysteine promotes atherosclerosis are not yet clearly defined. Arterial smooth muscle cells cultured in the presence of homocysteine grew to a higher density and produced and accumulated collagen at levels significantly above control values. Homocysteine concentrations as low as 50 μmol/L significantly increased both cell density and collagen production. Cell density increased by as much as 43% in homocysteine-treated cultures. Homocysteine increased collagen production in a dose-dependent manner. Smooth muscle cells treated with homocysteine at concentrations observed in patients with hyperhomocysteinemia had collagen synthesis rates as high as 214% of control values. Likewise, collagen accumulation in the cell layer was nearly doubled in homocysteine-treated cultures. Addition of aquacobalamin to homocysteine-treated cultures controlled the increase in smooth muscle cell proliferation and collagen production. These results indicate a cellular mechanism for the atherogenicity of homocysteine and provide insight into a potential preventive treatment.

So the bromelain, serrapeptase and nattokinase may be helpful again here - as long as homocysteine levels are controlled and thiamine/choline levels are adequate.

Well that's the overview of some of the research I've done, I'll see if I can post more relevant stuff later.

RedFox, HUGE thank you for posting this! :) I need to set some time aside to read everything from above before fully responding but it is not surprising that these things are so closely related.

I started taking L-Arginine recently for vascular health as it had been causing me weakness, fatigue and overall impacting health. It has conferred an amazing amount of energy back to my daily life. Greater or more efficient production of vasopressin perhaps has made a difference.

As for methylation and MTHFR gene mutilation - this, from what I have read, is maybe an underestimated occurrence genetically speaking. I don't know, nothing was conclusive but it has been associated with fibromyalgia, chronic fatigue etc. Methylated/co-enzymated/sublingual B vitamins seems to be crucial with this condition. Particularly B3, B6, B9 and B12. Trimethylglycine [TMG], L-methionine, glycine, choline are helpful so methylcobalamin, metafolin [methylfolate], non-flush niacinimide, P-5-P etc.

Thank you Shijing for starting this thread.
 

shijing

The Living Force
Re: Re: Endothelial dysfunction

LQB said:
I don't think the keto diet (as we refer to it) is high protein - protein should be restricted.

You're right -- corrected above.

LQB said:
Looks like there is a bazillion methylation support protocols out there - this blog post might help a bit: http://cfsmethylation.blogspot.com/2012/04/bumbling-around-methylation.html

Yes it does -- it also has some good links, so thank you.

LQB said:
In a recent WAPF article (http://www.westonaprice.org/cancer/cancer-to-the-rescue), Stephanie Seneff suggests the importance of sulfate in the body (and its transport) in relation to cancer. She suggests that an unacknowledged benefit of epsom salts is the sulfate (as opposed to the Mg), and that curcumin/turmeric are good sulfate transporters (besides anti-inflammatory/anti-oxidant). She doesn't mention methylation but there may be a connection considering how many pathways are involved.

It's a fascinating article, and would also be a good addition to the Cancer thread. Thanks again!

Redfox said:
Some things I've picked up along the way [...] Well that's the overview of some of the research I've done, I'll see if I can post more relevant stuff later.

This is all good information, and I appreciate you posting it. This video was good, and I sent it out to my extended family today:

RedFox said:

I also posted it to FB along with this video:


https://youtu.be/ZA8GUIRqIkE

These are the recommendations I pulled from it as I was taking notes:

  • Methylfolate (Deplin)
  • Methyl B-12 (absorbed under tongue: Jarrow)
  • Tetrahydrobiopterin BH4 (Nutrimedical.com – search for BH4 or mood balance)
  • NAC
  • Full spectrum minerals
  • Epsom salts
  • Vitamin B6 (P5P)
  • Vitamin C
  • DMG-Dimethylglycine or TMG
  • Zinc
  • Omega 3 fish oil
  • Vitamin E
  • Silymarin
  • Glutathione SR
  • Filtered water (reverse osmosis)
  • Vegetables and fruits
  • Heavy metal test

He also mentions how PCBs from plastic can contribute to the slowing of the methylation pathways -- I learned last weak that dental sealants can leach PCBs into the body, just like amalgams do with mercury :mad:

RedFox said:
Finally (for a wider scope on the MTHFR problem) Doctor Amy seems to have done some excellent research.
_http://www.dramyyasko.com/our-unique-approach/methylation-cycle/

I agree -- it looks like she also has a new book available here:

http://www.holisticheal.com/feel-good-nutrigenomics-your-roadmap-to-health-book.html

And here are a couple of MTHFR support and research sites:

http://mthfr.net/
http://mthfrsupport.weebly.com/index.html

There are also a number of books relevant to this topic -- some of them are pretty pricey, but here are the titles if anyone wants to look them up on Amazon:

Nutrigenetics: Applying the Science of Personal Nutrition
Nutrigenomics and Nutrigenetics in Functional Foods and Personalized Nutrition
Recent Advances in Nutrigenetics and Nutrigenomics, Volume 108
Nutrigenetics And Nutrigenomics (World Review of Nutrition and Dietetics)
Nutrigenetics
Impact of Nutritional Epigenomics on Disease Risk and Prevention: Special Topic Issue: 'Journal of Nutrigenetics and Nutrigenomics'
Nutritional Genomics: Discovering the Path to Personalized Nutrition
Genetic Bypass: Using Nutrition To Bypass Genetic Mutations (by Amy Yasko)
Methyl Magic: Maximum Health Through Methylation
The Methylation Miracle: Unleashing Your Body's Natural Source of SAM-e
The Homocysteine Revolution
The H* Factor Solution: *(Homocysteine​, the Best Single Indicator of Whether You are Likely to Live Long or Die Young)
Could It Be B12?: An Epidemic of Misdiagnoses
The Dynamic Genome and Mental Health: The Role of Genes and Environments in Youth Development
Nutritional Genomics: Impact on Health and Disease

Two books which I already have that have some information about this are Nutrient Power and Feed Your Genes Right. The former doesn't have an index for some reason, so I'm having to hunt through it linearly, but here are some sections from the latter on MTHFR:

p. 15 said:
How Jerry Saved His Heart

Jerry, now age fifty-six, is alive and well and in exceptionally good health – thanks to the fact that he has used nutrition to offset a potentially fatal defect.

Nearly all of the men in Jerry’s family have died at relatively young ages. His paternal grandfather died of a heart attack at forty-six. Jerry’s father died after suffering his second heart attack at age thirty-eight. And Jerry’s older brother died after a stroke at age forty-two.

Several years ago genetic testing found that Jerry carried a subtle defect in the gene programming the construction of methylenetetrahydrofolate reductase (MTHFR), an enzyme needed for normal utilization of the b vitamin folic acid. Because of this defect, Jerry did not efficiently use the modest levels of folic acid found in his diet. As a result his blood levels of homocysteine, a major risk factor for heart disease, were extremely high – 34 micromoles per liter of blood. It is very likely that other men in Jerry’s family carried the same MTHFR polymorphism.

To offset the sluggish MTHFR enzyme created by the gene, a nutritionally oriented physician recommended that Jerry take a daily high-potency B-complex vitamin supplement containing 800 mcg of folic acid. She also suggested that Jerry eat more vegetables and fewer high-carb and high-fat fast foods. Literally fearing for his life, Jerry also began exercising regularly and adopted stress-reduction habits, such as meditation, to deal with work-related pressures.

Today Jerry is a paragon of cardiovascular fitness. His homocysteine and blood-fat levels are normal, about 7 micromoles per liter of blood. In addition, his blood pressure is normal, and a treadmill test recently found him to be exceptionally fit.

p. 60 said:
Vitamins Help Crystal Have a Healthy Baby

Crystal, age thirty-three, had experienced more than her share of difficulties on the road to motherhood. During her twenties she miscarried once, gave birth to a stillborn baby, and delivered a son with spina bifida, a serious birth defect that led to his death several months later.

A new physician, looking at Crystal’s medical history, recommended that she undergo genetic testing for a subtle defect in the gene coding for methylenetetrahydrofolate reductase (MTHFR). MTHFR is an enzyme needed for the normal utilization of folic acid, and both the genetic defect and low folic acid intake have been associated with a higher risk of birth defects.

It turned out that Crystal did have that genetic defect, and a simple blood test also revealed that she had elevated levels of homocysteine, a sign of inadequate folic acid intake. Following her physician’s recommendation, Crystal began eating more spinach and dark green lettuces, good sources of folic acid, and taking a B-complex supplement plus 1,000 mcg of extra folic acid. Her doctor also recommended that she eat fewer sweets, because diets high in sugar have also been linked to a greater risk of birth defects.

Last year Crystal gave birth to a healthy eight-pound girl, and she and her husband are planning to have another baby in the next couple of years. Crystal’s improved eating habits and the B-vitamin supplements she now takes successfully counteracted an inborn genetic weakness.

p. 63 said:
Methylation Reactions and Molecule-Building Processes

[…] When methylation becomes sluggish, all of the subsequent molecule- and cell-building reactions begin to stall. One sign of sluggish or defective methylation is an elevation in the blood levels of homocysteine. Homocysteine is highly toxic and damages blood vessel walls, leading to the subsequent deposition of cholesterol, the body’s attempt to deal with the damage.

Elevated homocysteine levels were first proposed as a risk factor for coronary heart disease by Dr. Kilmer McCully in 1969, at a time when medicine was committed to the idea that excess cholesterol was a leading cause of heart disease. Since the early 1990s, hundreds of studies have confirmed homocysteine as a leading risk factor for heart disease, stroke, Alzheimer’s disease, and many other diseases.

Today many physicians routinely measure their patients’ levels of homocysteine to assess their risk of heart disease. (Ideal homocysteine levels are less than 6 micromoles per liter of blood, and levels above 13 micromoles per liter are a serious risk factor.) No drug will lower homocysteine levels; only folic acid, vitamins B6 and B12, choline, and betaine can. But despite considerable attention to homocysteine in the medical journals, most physicians see it only as a risk factor for heart disease, not as a sign of seriously impaired methylation and chemical reactions throughout the body. Furthermore, excess homocysteine is also toxic to the methylation process and to many different types of cells in the body, likely damaging brain cells and creating mutations that give rise to some cancer cells.

Some population groups, ranging from about 7 percent of Irish to perhaps as much as 42 percent of French Canadians, carry a subtle genetic defect (technically known as a polymorphism) that reduces their bodies’ ability to use folic acid efficiently. This genetic polymorphism produces an inefficient form of methylenetetrahydrofolate reductase (MTHFR), a key enzyme involved in using folic acid. Either a diet high in folic acid (found in dark leafy green vegetables) or folic acid supplements can offset this polymorphism, improve methylation, and lower homocysteine levels. The effect is comparable to “loading,” or saturating, MTHFR’s cellular environment with folic acid to improve its activity […]

There are also MTHFR-related sections on depression (p. 142-3), birth defects (p. 163-4), heart attack and stroke (p. 174), and neurotransmitters (p. 183-4).

Finally, the combination of genetic mutation and repeated reference to vegetables in regard to folic acid has me thinking about some topics in the transcripts (caveat: the following are condensed notes from my health file, not meant to replace the original transcripts -- if you want to look up the context, do a keyword search and it should get you there).

First, there is this part that was asked in relation to D'Adamo's books either directly or indirectly:

The Atkins diet for waistline okay, heart smart?! Naah! Atkins plan is good with two exceptions: suggest inclusion of bran fiber and liquid dairy, due to blood type, and need for elimination. This is greatly inhibited by “Atkins” plan, which is a fundamental flaw therein.

Regarding the diet you’re eating now: mostly fruits and vegetables and a little bit of meat. More protein needed for amino acids of a natural and balanced type. Stop amino acid supplements and eat meat. Your type needs the highest level and quality of protein.

The author of this blood type diet didn’t really just invent stuff out of his head, but the RH factor hones it in better. The RH factor will refine what this guy says exactly. It matters what type you are, and find out. The genotype diet is a very good start. It and the blood type diet have different goals. The genotype diet is more complete in a sense because it covers more genes and the blood type does just one.

What happened last time you had kogel mogel? This means that as a general rule, in terms of establishing brain chemistry generally speaking, it's good for everyone to stick to the blood type diet (closer), but don't obsess...

You should investigate blood type diet differentials, there is validity there.

The solution to hyperinsulism is more complicated than what you have read so far, but your RH factor is the key. There is more, but remember it is a mosaic. {I don't think this was in relation to D'Adamo, but I include it because it mentions RH factor}

Then possibly this (not sure):

You have this question from {XXXXX}: "It's about my difficulty with mammalian meat. Is there some reason besides leaky gut?" Incorrect formulation of the question. She does have a problem with mammalian meat, but that is not a feature of leaky gut. It is a feature of multiple system breakdown. Epigenetics mainly, but also specific genetic line problems. First, the gene expression has been altered after many years of abuse of the system design. This is something like what Gedgaudas writes about that once you’ve been eating carbs and grains and things for so many years, your body gets conditioned to it and it's very very difficult to switch over, and more. It is mostly reversible for {XXXXX}, but more difficult for her child who is third generation. Her mother has also put her system through improper use of the natural genetic profile.

Full siblings of schizophrenics are nine times more likely than the general population to have schizophrenia, and four times more likely to have bipolar disorder. XXXXX is affected by this genetic tendency -- oh indeed! However this requires explanation. First of all, the genetics that are associated with schizophrenia can be either a doorway or a barrier. Second, the manifestation of schizophrenia can take non-ordinary pathways. That is to say that diet can activate the pathway without the concomitant benefits. Primitive societies that eat according to the normal diet for human beings do not have "schizophrenics", but they do have shamans who can "see". When these genetic pathways are activated through wrong diet, it screws up the shamanic capacity. So, schizophrenia as you understand it or have witnessed it is a screw-up of something that could or might manifest in a completely different way on a different diet.

This seems directly relevant:

The cause of alzheimer’s disease is genetic. Biogenetic engineering can prevent it or lessen its effects, but will resolve anyway in the near future. And much other as well.

And there's always this to keep in the back of our minds:

The bloodlines that converge in the Percys and the Mortimers are incredible! You should know that these bloodlines become parasitically infected, harassed and tinkered with whenever a quantum leap of awareness is imminent. Such as “now.” We are talking about bloodlines becoming parasitically infested and harassed at times of quantum leaps such as now, when you were reading back over this, it seems that this is a repeating cycle, this parasitic infestation; and then reading the history of Gregory of Tours, and all of these truly amazing things - lights in the sky, plagues, repeated incidents of aerial phenomena... a ‘light like a serpent’ in the sky... a bright light and ‘snakes fell from the clouds...’ in 590, fiery globes traversed the heavens and then an eclipse of the sun. These astronomical phenomena were usually followed by inclement weather which, in its turn, brought plague... this may be the kind of parasitical infestation, harassment and so forth that we are talking about, look for more clues. Undulating matrix/mosaic. Wait for more... and good night.

In doing research earlier last and this year on pleomorphism and cancer (specifically the connection to molds and yeasts), there seemed to be a possible connection to 'parasitic infestation', possibly designed to respond to electrophonic effects. Now, this thing about MTHFR polymorphisms seems like it could fit the description of 'tinkering'. They seem common enough in the population, and are connected to so many autoimmune and psychological disorders and "diseases of modern civilization" which are connected to MTHFR when you watch the above videos, that it seems a little suspicious.
 

LQB

The Living Force
FOTCM Member
Re: Re: Endothelial dysfunction

Shijing said:
LQB said:
In a recent WAPF article (http://www.westonaprice.org/cancer/cancer-to-the-rescue), Stephanie Seneff suggests the importance of sulfate in the body (and its transport) in relation to cancer. She suggests that an unacknowledged benefit of epsom salts is the sulfate (as opposed to the Mg), and that curcumin/turmeric are good sulfate transporters (besides anti-inflammatory/anti-oxidant). She doesn't mention methylation but there may be a connection considering how many pathways are involved.

It's a fascinating article, and would also be a good addition to the Cancer thread. Thanks again!

Interesting - the Doc in the video you posted mentions epsom salts for the sulfate benefits.
 

shijing

The Living Force
Re: Re: Endothelial dysfunction

LQB said:
Interesting - the Doc in the video you posted mentions epsom salts for the sulfate benefits.

Yes, I noticed it was mentioned in both places too -- looks like I'll be picking up some epsom salts today. Oh, and thanks also for the coffee video you posted yesterday -- that was pretty interesting too!
 

Lilou

Ambassador
Ambassador
FOTCM Member
Re: Re: Endothelial dysfunction

I stopped using Epsom Salt sold locally. It is my understanding that it has not been purified and may contain contaminants such as lead, mercury, etc...If you soak in a hot tub with this, the contaminants are readly absorbed too.

I had always used regular ol' Epsom Salt, until one evening, following a soak in the tub, I just felt awful. Achy, lethargic, brain fog. Then I read up on it and was horrified to find it may or may not be pure. Now I order Magnesium Flakes, guaranteed pure from the Zechstein Mine in Holland. They are sold at Swanson Vitamins for $15/kilo. I highly recommend buying from a good source.
 

Gaby

SuperModerator
Moderator
FOTCM Member
Re: Re: Endothelial dysfunction

Speaking of mutations affecting MTHFR...

The SSRI/Folate Connection: Why Big Pharma May Want to Monopolize the B Vitamin You Can’t Live Without

_http://www.anh-usa.org/ssrifolate-connection/

If you missed our urgent Action Alert on the attempt to ban folate from dietary supplements, please take action now!

Last week we told you about FDA’s sneak attack on folate, the B9 vitamin essential to human life. This week, we tell you why the drug industry may want folate all to itself: it could be a ploy to make billions on a new, patented SSRI/folate combo drug.

Under the FDA’s new rules, Supplement Fact labels would only be allowed to list the term “folic acid” as an ingredient; the word “folate” would not be permitted. Oddly, this contradicts another FDA regulation that allows supplement producers to list sourcing ingredients next to nutrient names—for example, “Folic Acid (Folate).” Is the FDA attempting to overrule this old regulation via the new labeling rules?

This wouldn’t be a small labeling tweak: banning folate from the label is a sneaky way of banning it in the bottle, as it would be completely inaccurate and misleading to refer to dietary folates like folinic acid (5-FTHF), calcium methylfolate, various tetrahydrofolates, and other “whole food” folates as synthetic folic acid.

Why ban folate? Well, according to FDA “logic,” if dietary supplements can’t contain any folates except folic acid, all other folates would only be available from whole foods—or drugs. As clinicians learn more about genetic defects in the genes responsible for the fifteen or so enzymes needed to convert folic acid to the reduced forms of folate the body can use, drug companies have been dreaming of the billions they’d make by turning folate into an expensive patented drug. Now it looks like the FDA is trying to hand it to them on a silver platter.

Much of the population benefits from taking folate—as distinguished from folic acid—in dietary supplements. There are two key things to bear in mind: how much dietary folate you consume, and how much active folate you have available.

If most of your folate is coming from folic acid supplements rather than from food, you may still be gravely folate deficient because of the big variations in how efficiently folic acid is converted to the bioactive form in different people. Even if you got your folate from foods, it will depend not only on what leafy greens, beans, oranges, and other folate-rich sources you eat, but also on how you prepare your foods. Dietary folates are very sensitive to heat, so a lot is destroyed by cooking.

These days, many of us get most of our folate from supplements or fortified foods. We know a lot now about defects in two DNA sequences responsible for producing enzymes needed for the final stage of conversion of food folates and folic acid into the active form your body needs. These defects relate to an enzyme called MTHFR and are very common, though they vary enormously between ethnic groups and regions. The defects can be found in as many as 44% of North American Caucasians and over 50% of Italians. They are also more common among those predisposed to diseases such as cancer, heart disease, and autism, where the mutation frequency can exceed 90% of these populations. And that’s before you’ve even looked at mutations in other genes involved in folate metabolism such as DHFR, data for which has only been emerging recently.

Individuals with mutations affecting MTHFR or other genes relating to folate metabolism could suffer from an unhealthy buildup of unmetabolized folic acid if they have inadvertently taken too much folic acid for their own metabolism. Unmetabolized folic acid, as it turns out, is an emerging risk factor linked to increased risk of cancer, heart disease and stroke.

Researchers have also found a strong link between folate deficiency and depression. This is particularly interesting when you consider research showing that 70% of patients with major depressive disorder (MDD) carry the MTHFR mutation. Importantly, L-methylfolate, which completely bypasses the “damaged” MTHFR conversion step and delivers a “finished” folate the body can immediately use, has been proven to safely treat major depressive disorders with few to no side effects. L-methylfolate is readily available in some dietary supplements especially those supplied by practitioners—at least for the time being.

Of course, a gentle, natural, and cost-effective vitamin isn’t safe from drug companies: Merck, a Big Pharma heavyweight, holds the patents to Metafolin®, the “finished” and stabilized form of L-methylfolate. In addition to licensing Metafolin® to dietary supplement companies, Merck has worked with a Nestlé subsidiary to create Deplin®, a Metafolin® pill marketed as a medical food. Deplin® is designed to be taken in conjunction with SSRIs—a risky class of antidepressants linked to suicidal and violent behavior—for the treatment of depression.

With folate dietary supplements out of the way, Deplin®—which, as a medical food, is exempt from the FDA’s looming folate ban—could be in high demand, especially while folate based drugs are in the FDA pipeline. Merck clearly sees that it has something very valuable in its form of folate, as evidenced by their lawsuits to stop perceived patent infringement on Metafolin®. Additionally, Merck may see a Metafolin®/SSRI drug as a ticket to the golden days of blockbuster SSRI drugs like Prozac, Zoloft, and Paxil, all of which recently sailed off the so-called patent cliff.

Taking an old drug, combining it with another ingredient, and convincing the FDA to grant a monopoly on the “new” combo drug is a well-known Pharma trick: in 2013, Merck combined Zetia, its LDL-cholesterol lowering drug, with the generic version of Lipitor. Despite the fact that this drug did not reduce patients’ chances of developing heart disease, it was granted market exclusivity by the FDA.

What’s in it for the FDA? Thanks to user fees, much of the FDA is funded by Big Pharma—so when the drug industry’s coffers are threatened, so are the FDA’s.

URGENT Action Alert! The FDA must not be allowed to implement this change in its Supplement Facts rules. It will in effect ban the natural B vitamin folate and require supplement producers to use only the synthetic, oxidized form of folate, folic acid. Consumers who are less able to convert folic acid to the safe, reduced forms including the bioactive folate (5-MTHF) our bodies so badly need will have no choice but to use the drug version or die. Send your message to the FDA today, and tell them not to turn a critical, natural B vitamin into a drug through bureaucratic labeling sleight-of-hand!
 

H-KQGE

Dagobah Resident
Re: Re: Endothelial dysfunction

SMM said:
This video goes through some of the physical signs of methylation defects.

Thanks SMM. Some useful information there. I recognise the epicanthal folds & tongue tie in myself. I've been upping my B-vitamin intake for a little while now but I'll need to do more. Judging by those pictures, most people have at least one of those physical indicators, if not more. It's really sad how much we don't know about these things (and a great deal of doctors) & yet people are living their lives so far out of balance & passing these dysfunctions to the next generation. :(
 

shijing

The Living Force
Re: Re: Endothelial dysfunction

Lilou said:
I stopped using Epsom Salt sold locally. It is my understanding that it has not been purified and may contain contaminants such as lead, mercury, etc...If you soak in a hot tub with this, the contaminants are readly absorbed too.

I had always used regular ol' Epsom Salt, until one evening, following a soak in the tub, I just felt awful. Achy, lethargic, brain fog. Then I read up on it and was horrified to find it may or may not be pure. Now I order Magnesium Flakes, guaranteed pure from the Zechstein Mine in Holland. They are sold at Swanson Vitamins for $15/kilo. I highly recommend buying from a good source.

Thanks Lilou -- I also changed my mind about the Epsom Salts yesterday after talking with my doctor. Besides the contamination issue you mention, they're also contraindicated for people with certain polymorphisms (if I remember correctly, the CBS polymorphism is one to be concerned about). That means that if you have a particular polymorphism which you aren't aware of, you could use Epsom Salts and actually do more harm than good because it will interfere with your methylation train. He recommended magnesium chloride bath crystals from oceanmagnesium.com.

SMM said:
This video goes through some of the physical signs of methylation defects.

Thanks SMM -- it seems that body asymmetries in general are a good indicator that something might be amiss genetically (the internal ones are unfortunately hidden unless you use some sort of body imaging). Something else that seems to run in my family.

H-kqge said:
I recognise the epicanthal folds & tongue tie in myself. I've been upping my B-vitamin intake for a little while now but I'll need to do more. Judging by those pictures, most people have at least one of those physical indicators, if not more. It's really sad how much we don't know about these things (and a great deal of doctors) & yet people are living their lives so far out of balance & passing these dysfunctions to the next generation. :(

I'm really beginning to think that if it's within your means, it's a good idea for everyone to get tested for these things. They are much more common that I realized when I first started looking into this, and if you have one or more of them, then all of your best efforts spent toward adhering to the ketogenic diet, using supplements, and so forth may be for nought to a greater or lesser extent because your body isn't in a position to implement the changes (you'll still derive some benefits, but not all of the ones you should). This will be due to the body's inability to unload heavy metals and other toxins, which will then block the healing of the gut and balancing of the endocrine system among other things. A specific strategy seems to be necessary in order to detoxify (beyond what would be appropriate for "normal" people), but you won't know what it is unless you find out which polymorphisms you're carrying and what's required to compensate for them. Getting tested will also help you avoid generating some very expensive urine.

A good site to order a kit from, which some members seem to have already used successfully, is 23andme. I'm going to be ordering kits for my family later today.

Gaby said:
Speaking of mutations affecting MTHFR...

#Hating Big Pharma :rolleyes:
 

H-KQGE

Dagobah Resident
Re: Re: Endothelial dysfunction

Shijing said:
I'm really beginning to think that if it's within your means, it's a good idea for everyone to get tested for these things. They are much more common that I realized when I first started looking into this, and if you have one or more of them, then all of your best efforts spent toward adhering to the ketogenic diet, using supplements, and so forth may be for nought to a greater or lesser extent because your body isn't in a position to implement the changes (you'll still derive some benefits, but not all of the ones you should). This will be due to the body's inability to unload heavy metals and other toxins, which will then block the healing of the gut and balancing of the endocrine system among other things. A specific strategy seems to be necessary in order to detoxify (beyond what would be appropriate for "normal" people), but you won't know what it is unless you find out which polymorphisms you're carrying and what's required to compensate for them. Getting tested will also help you avoid generating some very expensive urine.

I was dreading the thought that all of the efforts spent on supplemental supports would be virtually useless. When I first started out reading the literature on genetics & such, I just focused on the diet & tried to get a handle on that, which is paying off now. Only since December have I really implemented supplements (wasted time buying stuff with fillers & undesirables - a necessary lesson learned there) & they are now having an effect, but nothing spectacular; this thread has given me the kick up the backside to get deeper into the research. I think I was just overwhelmed with all the dietary & psychology stuff (specifically psychopathy genes & autism) which hit me hard long after consciously processing the information.

Anyway, perhaps not new to you or any others currently looking into this but I thought it worthwhile to still post a video or two on MTHFR & the four-pronged (interrupted) methylation cycle. Both are from Benjamin Lynch (MTHFR.net link you provided) & go with the other videos provided by the others on this thread. First: https://m.youtube.com/watch?v=Mwn7RjSx3zM - Folate Metabolism and MTHFR: An Introduction - secondly:
https://m.youtube.com/watch?v=-lCQp0KkSB4 -Folate and Methylation Defects and Metabolism in 2013: Clinical Breakthroughs and Updates

The last one is pretty complex (to me at least) & he kind of whizzes through the presentation. It's a bit daunting to wrap my head around the small parts that I think I understand, the larger parts... well, like LQB said "Looks like there is a bazillion methylation support protocols out there."
 

LQB

The Living Force
FOTCM Member
Re: Re: Endothelial dysfunction

H-kqge said:
The last one is pretty complex (to me at least) & he kind of whizzes through the presentation. It's a bit daunting to wrap my head around the small parts that I think I understand, the larger parts... well, like LQB said "Looks like there is a bazillion methylation support protocols out there."

Yes, for example, Yasko's methylation protocol for autistic children is as complex as anything I've ever seen [her Step 3 is remyelination of the nerves - parts of which we could all probably use - http://www.dramyyasko.com/resources/autism-pathways-to-recovery/chapter-8/]

Here is a source for L-methylfolate mixed with B12/B6: http://hsfighters.bioactivhealth.com/ingredients.htm.
 
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