Folate

[Andypandy30]

Hi I would be interested to hear how other people raised their folate levels quickly by diet

[Technoid]

Whole grains, seeds, nuts, legumes, fruit and veggies. My tracker says I reach about 1mg of folate per day. (This is 2.5 times the RDA).

[Gambit62 Administrator]

Hi Andypandy30 - the mechanism for B12 absorption has some pecularities one of which is that the absorption from a meal in the ileum is very limited - to about 10mcg. I'm not aware of this sort of limitation applying to other vitamins so ensuring you have enough in your diet should be okay. You might need more than RDA if you have an absorption problem - very common for B12 and folate absorption problems to go together - but avoid really high doses of folate supplements as opposed to food.

[Bellabab in reply to Gambit62]

I have searched relentlessly for any harmful side effects from folic acid supplements & can find no scientifically valid studies. I have found suggestions that it causes cancer from USA sites yet no evidence to back it up. This response from USA is because Christian Fundamentalists oppose the supplementation of food with folic acid very strongly and crying cancer is a put off. If anyone can point me to good scientific evidence I would be grateful.

I take a 5mg folic acid tablet every other day and find this matches my B12 injection regime. At 81 I seem to be doing quite well.

[Technoid in reply to Bellabab]

After saying I wouldn't go on about the folic acid again I go back on my word 😆

As we discussed before, It is not clear that 5mg of folic acid (a dosage 25x the RDA) is necessary outside of correcting deficiency.

Since you have said previously that you do not eat a lot of folate-rich food it is not surprising that it would be necessary for you to supplement.

This is one example of a paper outlining some legitimate causes for concern:

Perspective: The High-Folate–Low-Vitamin B-12 Interaction Is a Novel Cause of Vitamin B-12 Depletion with a Specific Etiology—A Hypothesis

sciencedirect.com/science/a...

"We hypothesize that excessive intake of folic acid depletes serum holotranscobalamin (holoTC), thereby decreasing active vitamin B-12 in the circulation and limiting its availability for tissues."

"this hypothesis explains the findings from 2 large cross-sectional studies, NHANES and SALSA (40, 41), that show the classic association of vitamin B-12 biomarkers (tHcy and MMA) with vitamin B-12 status is paradoxical when a vitamin B-12 insufficiency state is accompanied by high folate (Figures 4 and 5).

Further support for the hypothesis comes from the study described above in which folic acid supplements were mistakenly prescribed to vitamin B-12–deficient patients"

[Technoid in reply to Technoid]

The full hypothesis is as follows:

"It is hypothesized that exposure to excess folic acid (via supplements and fortified foods) causes exacerbation of vitamin B-12 deficiency by binding to folic acid receptors (FR; red triangles) in the bone marrow and the renal proximal tubule cells. This leads to diversion of the limited supply of serum TC-B12 (depicted by thick black arrows) to the bone marrow to support folic acid–mediated hematopoiesis and reticulocyte formation, or into the urine by possibly interfering with TC-B12 uptake via the megalin/cubilin/amnionless receptor complex in the renal proximal tubule cells or by some other mechanism yet to be elucidated. The TC-B12 is diverted away from other tissues (e.g., liver and brain; depicted by thin dashed arrows). This leads to accentuated elevations in Hcy and MMA concentrations in serum (also depicted by thick black arrows) and exacerbation of neurodegeneration"

From the abstract:

"This hypothesis is drawn from evidence of observational and intervention studies of vitamin B-12–deficient patients and epidemiological cohorts. The evidence also suggests that, in a depleted state, vitamin B-12 is diverted to the hematopoietic system or the kidney."

[Technoid in reply to Technoid]

Additionally, there is this in-vitro study to consider:

"Excessive Folic Acid Mimics Folate Deficiency in Human Lymphocytes

mdpi.com/1467-3045/44/4/97

"In summary, our findings corroborate what others have uncovered in various models. Deficient and excessive levels of FA similarly impact global DNA methylation, cytome biomarkers, and DNA repair gene expression. While the specific mechanism underlying the observed effects requires additional research, the accumulation of evidence from recent reports warrants a fresh perspective on the role of folic acid fortification in health and disease."

and this one:

Folic acid depletion as well as oversupplementation helps in the progression of hepatocarcinogenesis in HepG2 cells

pubmed.ncbi.nlm.nih.gov/361...

"Folate ingestion below and above the physiologic dose has been shown to play a tumorigenic role in certain cancers. Also, excessive folate supplementation after establishment of pre-established lesions led to an advancement in the growth of a few tumors."

and this mouse-model study:

Excess folic acid intake increases DNA de novo point mutations

"Our data indicate that FA supplementation should be restricted to an ideal benefit range. Both insufficient folate and excess FA intake are risk factors for genome and epigenome instability. The genome and epigenome impairment induced by either high FA or low FA diets should be further confirmed in human population in future studies."

this workshop outcome:

Knowledge gaps in understanding the metabolic and clinical effects of excess folates/folic acid: a summary, and perspectives, from an NIH workshop (2020)

ncbi.nlm.nih.gov/pmc/articl...

"At present, there is an insufficient body of evidence to support human adverse health outcomes that are a result of high amounts of folate or folic acid intake. However, owing to a provocative body of observations and the potential public health ramifications of these observations, a comprehensive and rigorous body of future investigations is warranted to determine if there is a causal relation. "

this review:

Safety Of Folic Acid (2018)

ncbi.nlm.nih.gov/pmc/articl...

"Additional research is needed to assess the health effects of folic acid supplement use when the current UL for folic acid is exceeded"

and this review:

Uncovering the Hidden Dangers and Molecular Mechanisms of Excess Folate: A Narrative Review (2023)

ncbi.nlm.nih.gov/pmc/articl...

"The literature presents compelling evidence that excess folate disrupts one-carbon metabolism, significantly impacting methylation reactions. It remains unclear whether the resulting epigenetic changes are caused solely by the direct disruption of one-carbon metabolism by excess FA or if other unidentified pathways are involved."

The 2023 EFSA scientific opinion on the tolerable upper intake level for folate called for further research in many areas relating to excess folate:

• "Further research is required regarding all groups of the population to characterise potential critical effects of excess folate intake. This should address potential differences in the toxicity profile of the various forms of folate added to foods and used in food supplements. Also, investigations of the potential vulnerability of specific subgroups of the population, such as infants and children, pregnant women and older adults, is needed, taking into account specific issues in terms of absorption, metabolism, distribution and excretion of various folate forms in these groups.

• Further investigation of the relationship between high folate intake and the risk of cancer is needed, including colorectal and prostate cancer. Additional research is needed on the relationship between high folate intake and the risk of SSA/Ps.

• Further research is required to clarify the impact of high doses of folic acid and 5‐MTHF on brain structures and functions.

• Research is needed to investigate whether the epigenetic changes found in interventions with high doses of folic acid in some populations are causally related to alterations in any phenotypic characteristics. Research is also needed in that respect on the other forms of folate.

• Additional research on UFA is required, in particular whether UFA can specifically affect biological pathways leading to adverse health effects.

• Data on the consumption of fortified foods and food supplements containing folic acid and/or 5‐MTHF salts in EU populations are scarce. For the risk characterisation, there is a need to generate more and harmonised data on folate intake in its different forms from food supplements and fortified foods among users of those products."

ncbi.nlm.nih.gov/pmc/articl...

There is not enough evidence to say with certainty that intakes of 5mg of folic acid are safe long-term, and there is almost nothing that would suggest that they are necessary outside of quickly correcting a severe folate deficiency. Insufficient evidence of harm is not evidence of safety.

There is emerging evidence and physiological plausability that points to very high folic acid intakes possibly having a negative effect on B12 availability and function and potentially other negative health effects too.

Although this is somewhat of an appeal to history, it can also be noted that prior to the formulation of folic acid in 1946, the normal intake of dietary folic acid would have been 0mcg. This doesn't automatically imply that it is a bad thing to consume per se, but its certainly a new substance to our bodies and in my mind, supplementing it is much more comparable to taking a medication than to supplementing a common food ingredient or food component. The application of the precautionary principle to such a substance, is I think, quite warranted.

Conversely, there is good evidence that 400mcg or less of folic acid is a safe dosage, for those that need it. Certain groups may benefit from up to 800mcg in forms such as methylfolate or folinic acid, which are safe and more closely comparable to the folates provided in food sources.

In summary, I think the current body of evidence warrants being somewhat cautious about very high levels of folic acid supplementation, especially those which are far in excess of the tolerable upper limit (1mg).

[Corney23uk]

I am doing exactly this at the moment and seeing really positive results - I can't seem to absorb any kind of folate from tablets and have had low folate for over 14 years. So what I am doing is- I have a smoothie every morning (it is a frozen Pret one) with spinach, kale, and avocado and you add apple juice so it doesn't taste too bad. For a snack I am having avocado and prawns, sometimes twice a day - then I am doing things like have cauliflower cheese with broccoli instead of cauliflower and also liver etc. I have had my first positive folate blood test but I am having to eat 3 to 4 times the RDA.