Folic Acid, Insulin Resistance, ED, CKD

redsun

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Dec 17, 2018
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I put together some studies on folic acid(folate) here seeing as there isn't much on it on this forum. I'd thought I'd do my part in adding something useful here.

Chronic folate deficiency induces glucose and lipid metabolism disorders and subsequent cognitive dysfunction in mice. - PubMed - NCBI

"Previous studies have shown that folate levels were decreased in patients with type 2 diabetes (T2D) and further lowered in T2D patients with cognitive impairment."

"Seven-week-old mice were fed with either a CFD or control diet for 25 weeks. Serum folate was significantly reduced, whereas serum total homocysteine was significantly increased in the CFD group. Moreover, CFD induced obesity after a 6-week diet treatment, glucose intolerance and insulin resistance after a 16-week-diet treatment."

"After a 24-week diet treatment, CFD induced anxiety-related activities and impairment of spatial learning and memory performance."

Association of low dietary folate intake with lower CAMKK2 gene methylation, adiposity, and insulin resistance in obese subjects. - PubMed - NCBI

"Subjects with total folate intake lower than 300μg/d showed more fat mass (especially trunk fat), as well as statistically higher levels of glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR) index, cortisol, and plasminogen activator inhibitor-1 than those consuming at least or more than 300μg/d."

Folic acid supplementation alters the DNA methylation profile and improves insulin resistance in high-fat-diet-fed mice. - PubMed - NCBI

"Mice were fed a high-fat diet (HFD), normal diet (ND) or an HFD supplemented with folic acid (20 μg/ml in drinking water) for 10 weeks..."

"FA supplementation reduced the fat mass and serum glucose levels and improved insulin resistance in HFD-fed mice. "

"Pathway analyses showed novel DNA methylation changes in adipose genes associated with insulin secretion, pancreatic secretion and type 2 diabetes. "

"FA supplementation improved insulin resistance, decreased the fat mass, and induced DNA methylation and gene expression changes in genes associated with obesity and insulin secretion in obese mice fed a HFD."

Low serum folic acid can be a potential independent risk factor for erectile dysfunction: a prospective case-control study. - PubMed - NCBI

"The purpose of the study was to compare serum level of folic acid (FA) in patients with erectile dysfunction (ED) versus healthy controls and to assess its correlation with other well-known confounders for ED."

"Our study revealed that the median FA of the cases and the controls were 7.1 ng/mL and 13.4 ng/mL, respectively, and this difference was of high statistical significance (p < 0.001)."

"Serum FA level decreased as the severity of ED increased even after adjustment of age, serum testosterone, DM, HTN, and smoking. FA deficiency might be an independent risk factor of ED."

Effect of chronic kidney disease on the expression of thiamin and folic acid transporters. - PubMed - NCBI

"While plasma folate and thiamin levels are generally normal in patients with CKD, they commonly exhibit features resembling vitamin deficiency states. Earlier studies have documented impaired intestinal absorption of several B vitamins in experimental CKD. In this study, we explored the effect of CKD on expression of folate and thiamin transporters in the key organs and tissues."

"Plasma folate and thiamin levels were similar between the CKD and the control groups. However, expressions of both folate (RFC and PCFT) and thiamin (THTR-1, THTR-2) transporters were markedly reduced in the small intestine, heart, liver and brain of the CKD animals. Liver protein abundance of folate and thiamin transporters was significantly reduced in the CKD animals when compared with the sham-operated controls. Furthermore, we found a significant reduction in mitochondrial folate and thiamin transporters in the CKD animals."

I plan to add more studies regularly as I find them.
 

Cirion

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Probably one of the reasons OJ is a common recommendation of Peat, it's pretty rich in folate, especially if you drink several cups a day. I did realize a couple of weeks ago I was a little low on folate, but increasing OJ has brought my intake into the green (more than the 300 microgram threshold noted here).
 

BigChad

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Jun 28, 2019
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I put together some studies on folic acid(folate) here seeing as there isn't much on it on this forum. I'd thought I'd do my part in adding something useful here.

Chronic folate deficiency induces glucose and lipid metabolism disorders and subsequent cognitive dysfunction in mice. - PubMed - NCBI

"Previous studies have shown that folate levels were decreased in patients with type 2 diabetes (T2D) and further lowered in T2D patients with cognitive impairment."

"Seven-week-old mice were fed with either a CFD or control diet for 25 weeks. Serum folate was significantly reduced, whereas serum total homocysteine was significantly increased in the CFD group. Moreover, CFD induced obesity after a 6-week diet treatment, glucose intolerance and insulin resistance after a 16-week-diet treatment."

"After a 24-week diet treatment, CFD induced anxiety-related activities and impairment of spatial learning and memory performance."

Association of low dietary folate intake with lower CAMKK2 gene methylation, adiposity, and insulin resistance in obese subjects. - PubMed - NCBI

"Subjects with total folate intake lower than 300μg/d showed more fat mass (especially trunk fat), as well as statistically higher levels of glucose, insulin, homeostatic model assessment-insulin resistance (HOMA-IR) index, cortisol, and plasminogen activator inhibitor-1 than those consuming at least or more than 300μg/d."

Folic acid supplementation alters the DNA methylation profile and improves insulin resistance in high-fat-diet-fed mice. - PubMed - NCBI

"Mice were fed a high-fat diet (HFD), normal diet (ND) or an HFD supplemented with folic acid (20 μg/ml in drinking water) for 10 weeks..."

"FA supplementation reduced the fat mass and serum glucose levels and improved insulin resistance in HFD-fed mice. "

"Pathway analyses showed novel DNA methylation changes in adipose genes associated with insulin secretion, pancreatic secretion and type 2 diabetes. "

"FA supplementation improved insulin resistance, decreased the fat mass, and induced DNA methylation and gene expression changes in genes associated with obesity and insulin secretion in obese mice fed a HFD."

Low serum folic acid can be a potential independent risk factor for erectile dysfunction: a prospective case-control study. - PubMed - NCBI

"The purpose of the study was to compare serum level of folic acid (FA) in patients with erectile dysfunction (ED) versus healthy controls and to assess its correlation with other well-known confounders for ED."

"Our study revealed that the median FA of the cases and the controls were 7.1 ng/mL and 13.4 ng/mL, respectively, and this difference was of high statistical significance (p < 0.001)."

"Serum FA level decreased as the severity of ED increased even after adjustment of age, serum testosterone, DM, HTN, and smoking. FA deficiency might be an independent risk factor of ED."

Effect of chronic kidney disease on the expression of thiamin and folic acid transporters. - PubMed - NCBI

"While plasma folate and thiamin levels are generally normal in patients with CKD, they commonly exhibit features resembling vitamin deficiency states. Earlier studies have documented impaired intestinal absorption of several B vitamins in experimental CKD. In this study, we explored the effect of CKD on expression of folate and thiamin transporters in the key organs and tissues."

"Plasma folate and thiamin levels were similar between the CKD and the control groups. However, expressions of both folate (RFC and PCFT) and thiamin (THTR-1, THTR-2) transporters were markedly reduced in the small intestine, heart, liver and brain of the CKD animals. Liver protein abundance of folate and thiamin transporters was significantly reduced in the CKD animals when compared with the sham-operated controls. Furthermore, we found a significant reduction in mitochondrial folate and thiamin transporters in the CKD animals."

I plan to add more studies regularly as I find them.

Is synthetic folic acid fine to use though or do these benefits only apply to folate in foods and methylfolate supps
 
OP
redsun

redsun

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Probably one of the reasons OJ is a common recommendation of Peat, it's pretty rich in folate, especially if you drink several cups a day. I did realize a couple of weeks ago I was a little low on folate, but increasing OJ has brought my intake into the green (more than the 300 microgram threshold noted here).

Probably not a good idea to just slide near the bare minimum of 400mcg. It would likely be wise to go higher. I dont know how long your folate intake has been low, but if it has been low for quite a while(weeks or longer) that is likely going to exacerbate insulin resistance and glucose intolerance just like going low on any B vitamin will and it doesn't take long to cause problems. I remember awhile ago reading you can show signs of B2 deficiency in days for example.

If you were to think on a whole foods based diet what your intake of B9 would be, assuming it was diverse(starches, vegetables, fruits, and animal products) you easily reach 400mcg and usually end up with much more depending on what you eat.

Is synthetic folic acid fine to use though or do these benefits only apply to folate in foods and methylfolate supps

The studies likely used folic acid as that's what they state. Some are fearful of it but I am not convinced. Its a good idea to get folate from foods regardless whether you decide to take it along with a B complex or on it's own.
 

BigChad

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Jun 28, 2019
Messages
747
Probably not a good idea to just slide near the bare minimum of 400mcg. It would likely be wise to go higher. I dont know how long your folate intake has been low, but if it has been low for quite a while(weeks or longer) that is likely going to exacerbate insulin resistance and glucose intolerance just like going low on any B vitamin will and it doesn't take long to cause problems. I remember awhile ago reading you can show signs of B2 deficiency in days for example.

If you were to think on a whole foods based diet what your intake of B9 would be, assuming it was diverse(starches, vegetables, fruits, and animal products) you easily reach 400mcg and usually end up with much more depending on what you eat.



The studies likely used folic acid as that's what they state. Some are fearful of it but I am not convinced. Its a good idea to get folate from foods regardless whether you decide to take it along with a B complex or on it's own.

I heard most risks of folic acid are from not metabolising it properly. If you take creatine that should make it easier to handle supplemental folic acid due to the decreased load on the methylation cycle?
 
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redsun

redsun

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I heard most risks of folic acid are from not metabolising it properly. If you take creatine that should make it easier to handle supplemental folic acid due to the decreased load on the methylation cycle?

I've heard of that. That's up to you if you want to. Though in general Bs should be taken as a whole(B-complex) as its hard to know what can happen with extended periods of single vitamin supplementation.
 

cihans

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Aug 1, 2017
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I've heard of that. That's up to you if you want to. Though in general Bs should be taken as a whole(B-complex) as its hard to know what can happen with extended periods of single vitamin supplementation.
Hi do you have specific brand to suggest FA supplementation?
 
EMF Mitigation - Flush Niacin - Big 5 Minerals

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