B12/Folic Acid and D3/K2 Supplementation

[Arnie Pye]

The paper also includes iron deficiencies.

I'll check it out.

 

[Mij]

I do not appear to suffer from a B12 deficiency, at least taking more does not improve things, and I would appear to have too much iron (inferred from my ferritin level). It is something I considered a 'while' back.

I didn't have symptoms of B12 deficiency, but when I was tested years ago I was borderline low. I took B12 shots and methB12 tablets but didn't feel any difference. So who knows.

 

[Mij]

The funny thing is that my GP didn't feel I needed to supplement with B12 when it was borderline low, but a couple of years later after taking B12 tablets and retested, she had the receptionist call to tell me to immediately stop taking it b/c it was 'high!".

 

[Arnie Pye]

I've heard/read that many doctors think that B12 is toxic.

A quote from this link : https://stichtingb12tekort.nl/engli...been-shown-to-be-safe-for-more-than-50-years/

The safety of vitamin B12 treatment is further illustrated by the decennia long use of hydroxocobalamin as an antidote for cyanide poisoning, often caused by smoke inhalation. In the Netherlands ambulances, fire departments and emergency rooms have the Cyanokit at their disposal. In life threatening situations 5 g hydroxocobalamin is given intravenously within 15 minutes, an amount that corresponds with 5 000 injections of 1 mg B12.[10] Hydroxocobalamin reacts in the body with cyanide, and forms cyanocobalamin, which is excreted in urine.
The serum value of B12 can rise to an average of 560 000 000 pmol/L within 50 minutes.[11] If necessary this treatment is repeated within several hours, making the total dose 10 grams. The side effects that occur, like reddening of the skin and urine and changes in heart rate and blood pressure are temporary and harmless. In short: 10 000 injections a day are still not enough for an overdose of vitamin B12.

 

[Sly Saint]

A recent survey highlighted that increased dietary intake of folic acid causes adverse health effects by promoting angiogenesis, inflammation, and neurotoxicity.

Scientists have recently reviewed the existing literature to understand the effect of increased dietary intake of folic acid on human health.

This review, published in Nutrients, also summarizes the proposed mechanisms through which dietary folic acid interacts with hypoxia to influence health outcomes.

The role of folic acids in humans
Folates are B vitamins that play a critical role in cellular growth and development. During pregnancy, women are advised to consume adequate amounts of folic acid to help reduce the risk of neural tube defects (NTDs) in the developing fetus. While the protective effect of folic acid against NTDs is well-established, the exact biological mechanism behind it remains unclear.

Folic acid is a key player in one-carbon (1C) metabolism, which supports vital processes such as DNA repair, nucleotide synthesis, and lipid metabolism. It also contributes to the generation of methyl groups, which are essential for the remethylation of homocysteine—a process important for maintaining cellular health and function.

Increased and reduced intake of folic acid in adults
Studies in mouse models have shown that high daily intake of folic acid in adults can lead to adverse health effects. These negative outcomes may stem from disruptions in the one-carbon (1C) metabolic pathway, including impaired folic acid receptor function and altered enzyme expression. However, more comprehensive research is needed to fully understand how elevated folic acid levels affect human health.

On the other hand, insufficient folic acid intake can result in elevated homocysteine levels, as the body lacks enough methyl groups to convert homocysteine back to methionine. High homocysteine levels are associated with an increased risk of cardiovascular diseases, including ischemic stroke.

Some studies have indicated that higher folic acid levels may enhance endothelial cell function—a key marker of cardiovascular health. Experimental research suggests that folates support endothelial function by boosting antioxidant activity and facilitating direct interactions with endothelial nitric oxide synthase (NOS).

Vitamin B12 and folic acid actions
Vitamin B12 is involved with the recycling and regulation of 1C metabolism. This vitamin is necessary for various metabolic functions including red blood cell synthesis, macrocytic anemia, and reduction of the risk of neural tube defects.
Vitamin B12 deficiency can trap folic acid metabolites (e.g., 5-MTHF) and cause inhibition in the re-methylation of homocysteine.
A decrease in homocysteine remethylation may lead to neuropathy, megaloblastic anemia, and neuropsychiatric disorders. Individuals with normal B12 levels and high folic acid levels could be at a high risk of cognitive impairment through the accumulation of homocysteine.

Sleep apnea and folic acid metabolism
Obstructive sleep apnea (OSA) is a breathing disorder that may lead to cognitive deficits and cardiovascular diseases via hypoxia. Folic acid is associated with antioxidant pathways that help prevent cognitive decline and cardiovascular diseases linked to OSA.

Previous studies have indicated that increased folic acid intake triggers OSA development due to A methylation discrepancies associated with improper responses to hypoxia.

What happens if you significantly increase dietary folic acid intake?

Journal reference:

• Gunnala, S. et al. (2025) How Increased Dietary Folic Acid Intake Impacts Health Outcomes Through Changes in Inflammation, Angiogenesis, and Neurotoxicity. Nutrients. 17(7), 1286. doi: https://doi.org/10.3390/nu17071286
  

 

[Arnie Pye]

If folate levels are low then someone improves their level it can have positive effects :

Title : Folic Acid Treatment Is Associated With Decreased Risk of Suicide Attempts

Link : https://neurosciencenews.com/folic-acid-suicide-21568/

.

But taking the level too high can have adverse effects in some groups of patients :

Title : High serum folate is associated with brain atrophy in older diabetic people with vitamin B12 deficiency

Link : https://link.springer.com/article/10.1007/s12603-017-0979-z

.

More evidence of adverse outcomes with excessive folic acid :

Title : Excessive folic acid intake and relation to adverse health outcome

Link : https://www.sciencedirect.com/science/article/abs/pii/S0300908416300530

.

Title : The Methylene Tetrahydrofolate Reductase (MTHFR) isoform challenge. High doses of folic acid are not a suitable option compared to 5 Methyltetrahydrofolate treatment

Link : https://www.semanticscholar.org/paper/The-Methylene-Tetrahydrofolate-Reductase-(MTHFR)-of-Servy-Menezo/1a92716f3f0b38334b48a4c787ba8b966e3f97b9?p2df

The above link is useful for having quite a lot of citations and references relating to folic acid, folate and MTHFR.

.

Title : Active Folate Versus Folic Acid: The Role of 5-MTHF (Methylfolate) in Human Health

Link : https://pmc.ncbi.nlm.nih.gov/articles/PMC9380836/

.

 

[Murph]

I started taking some fizzy b-vitamins a while ago. I perceive a benefit over a short-tun time horizon, perhaps 1-4 hours.

I've recently tried to be a lot more skeptical about what it is in any product that might be delivering the benefit. I had a good look at what they put in these tablets. The 'non-active' ingredients are not listed but from my reading on similar products, one of the ingredients is likely to be sodium bicarbonate. I remember seeing threads suggesting that compound helped some people a long time ago; it sounds like a home remedy for sure but there's papers suggesting it improves athletic performance.

Mechanistic Insights into the Efficacy of Sodium Bicarbonate Supplementation to Improve Athletic Performance - PubMed

A large proportion of empirical research and reviews investigating the ergogenic potential of sodium bicarbonate (NaHCO₃) supplementation have focused predominately on performance outcomes and only speculate about underlying mechanisms responsible for any benefit. The aim of this...

pubmed.ncbi.nlm.nih.gov

I don't seem to get any benefit from taking b-vitamins in a non-fizzy format. (The ones I use are the aldi dissolving brand).

So I am about to dissolve some bicarb soda in a glass of water and see if I notice anything! This is not a blinded test but it is science of a sort, trying to isolate ingredients and gather data on perceived effects.

 

[Arnie Pye]

I don't seem to get any benefit from taking b-vitamins in a non-fizzy format

Have you tried B vitamins in different formats? For example :

Methylfolate instead of folic acid

Methylcobalamin instead of cyanocobalamin, hydroxocobalamin, or adenosylcobalamin

Pyridoxal-5-Phosphate instead of Pyridoxine Hydrochloride

etc...

 

[PrairieLights]

I also have hypothyroidism and as a result my vitamins were low. As the doctor was uninterested, I have worked on all my levels myself and have monitored them via private blood tests to maintain safe levels accordingly.

Serum b12 is the only one that refuses to be raised though the active b12 range is lerfect. I have been tested for b12 mma which came back negative. I do understand the tests are difficult and often inaccurate.

From the start to now, I am unaware of feeling an improvement from improving my vitamin levels. I was wondering if that was another sign of me/cfs as others I know feel a huge boost after a month whereas I have worked on building and maintaining for well over a year and feel the same.

 

[Mij]

So I am about to dissolve some bicarb soda in a glass of water and see if I notice anything! This is not a blinded test but it is science of a sort, trying to isolate ingredients and gather data on perceived effects.

There are studies with mixed results but it's worth a try.

One here that mixes caffeine and SB.

Abstract​

Caffeine and sodium bicarbonate are extensively researched ergogenic aids known for their potential to enhance exercise performance. The stimulant properties of caffeine on the central nervous system, coupled with the buffering capacity of sodium bicarbonate, have been associated with improved athletic performance. This has led to investigations of their combined effects on strength.

The aim of the present study is to investigate the effect of isolated and combined caffeine and sodium bicarbonate consumption on strength using the isometric mid-thigh pull test (IMTP). Nineteen male college students (age 23.6 ± 1.6 years) participated in this crossover, double-blind, placebo-controlled study. They were exposed to the following conditions: control (no supplement), placebo (20 g maltodextrin), caffeine (6 mg/kg), sodium bicarbonate (0.3 g/kg), and a combination of caffeine and sodium bicarbonate.

Supplements and placebo were diluted in water and consumed 60 min prior to the IMTP tests. Two 5 s IMTP trials were performed at 40–60% and 60–80% of One Repetition of Maximum (1RM) with a 60 s rest between. Consumption of caffeine or Caf + NaHCO3 did not significantly change peak IMTP strength values at any intensity (p = 0.110). The peak IMTP values did not show significant differences between conditions or from control condition values (1091 ± 100 N) to Caf (1224 ± 92 N), NaHCO3 (1222 ± 74 N), and Caf ± NaHCO3 (1152 ± 109 N).

However, the test of the results of the ANOVA analysis of repeated measures of effect within the caffeine condition was significant for the increase in IMTP relative strength compared to control (p < 0.05). Thus, the IMTP force values increased significantly from control to Caf (p = 0.016) and from Pla to Caf (p = 0.008), but not for other comparisons (p > 0.05). In summary, caffeine supplementation alone, taken 60 min before exercise, positively affects submaximal strength performance. In contrast, sodium bicarbonate, whether taken alone or in combination with caffeine, does not enhance submaximal strength in the IMTP tests.

Link

 

[Mij]

Caffeine boosts my energy for an hour, but totally exhausts it for the remainder of the day. I tried SB pre exercise but I can't say it helped in any way.

 

[Mij]

From the start to now, I am unaware of feeling an improvement from improving my vitamin levels. I was wondering if that was another sign of me/cfs as others I know feel a huge boost after a month whereas I have worked on building and maintaining for well over a year and feel the same.

I had a whole panel of tests done over 20yrs ago and was given a 'custom formula' that cost $$$ and it did squat for me. The only supplement that improved my energy was mg/taurine injections, the effects were immediate (within a day). Also taking fish oils was good.

 

[Arnie Pye]

I also have hypothyroidism and as a result my vitamins were low. As the doctor was uninterested, I have worked on all my levels myself and have monitored them via private blood tests to maintain safe levels accordingly.

Serum b12 is the only one that refuses to be raised though the active b12 range is lerfect. I have been tested for b12 mma which came back negative. I do understand the tests are difficult and often inaccurate.

From the start to now, I am unaware of feeling an improvement from improving my vitamin levels. I was wondering if that was another sign of me/cfs as others I know feel a huge boost after a month whereas I have worked on building and maintaining for well over a year and feel the same.

Perhaps you should be tested for Pernicious Anaemia (PA)? Apart from having read that PA testing is unreliable I don't know much about it.

 

[PrairieLights]

Perhaps you should be tested for Pernicious Anaemia (PA)? Apart from having read that PA testing is unreliable I don't know much about it.

Yes. I was tested for the MMA which I think might be an enzyme or something and my test was negative... which is apparently common and unreliable like you say.

My GP thinks that's that but my endo flagged my b12 serum as low but didn't recommend treatment. I do take high dose supplements daily to maintain at least.

Edited to add: I definitely had malabsorption to start but I have signs that this has improved as my thyroid treatment has improved. Only b12 serum and calcium remains an issue. Calcium is being retested off supplements, did it last week but the nurse contaminated the specimen so redoing tomorrow. I have been self treating calcium for many years.