Reduced folate intake may extend lifespan, by restoring metabolic flexibility
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Ever since we launched our B-complex product Energin almost 10 years ago, we have been getting emails about why the product does not contain folic acid and vitamin B12. I keep answering by saying that both of those vitamins have been linked to higher risk of cancer, and as such have stubbornly resisted demands to add those 2 vitamins to the product. Now, the study below adds another good reason to not take folate supplement in adulthood – reduced folate intake may increase lifespan. Interestingly, the mechanism of action for lifespan extension by folate restriction is that dietary folate deficiency seems to restore metabolic flexibility – a hallmark of youth. While we easily switch between burning carbs and fat in our childhood and early adulthood, that flexibility declines as we age. Very old (or sick) people burn predominantly fat, even in the presence of sufficient glucose intake. This lack of metabolic flexibility is likely driven by a steady decline in thyroid function as we age, which results in compensatory increase in adrenal activity, with the end result being that older people are in a state of chronic stress even when undisturbed, which results in excessive lipolysis and thus dominance of fat oxidation as per the Randle Cycle. Whether restricting dietary folate results in increased thyroid function, reduced adrenal hyperactivity, or both remains to be discovered. Be that as it may, the main (indirect) finding of the study seems to be that lifespan is metabolically controlled, and restoring youthful metabolic profile can extend lifespan.
https://pubmed.ncbi.nlm.nih.gov/38260683/
“…Folate is a vitamin required for cell growth and is present in fortified foods in the form of folic acid to prevent congenital abnormalities. The impact of low folate status on life-long health is poorly understood. We found that limiting folate levels with the folate antagonist methotrexate increased the lifespan of yeast and worms. We then restricted folate intake in aged mice and measured various health metrics, metabolites, and gene expression signatures. Limiting folate intake decreased anabolic biosynthetic processes in mice and enhanced metabolic plasticity. Despite reduced serum folate levels in mice with limited folic acid intake, these animals maintained their weight and adiposity late in life, and we did not observe adverse health outcomes. These results argue that the effectiveness of folate dietary interventions may vary depending on an individual’s age and sex. A higher folate intake is advantageous during the early stages of life to support cell divisions needed for proper development. However, a lower folate intake later in life may result in healthier aging.”
“…A new study suggests that while consuming folates is considered healthy for everyone — and it clearly benefits the young — it may result in metabolic issues for older individuals. The study of mice from Texas A&M University’s AgriLife Research found that lower levels of folates, the naturally occurring form of vitamin B9, facilitated the transition from sleep metabolism to waking metabolism…The study’s senior author, Michael Polymenis, PharmD, PhD, who teaches biochemistry and biophysics at Texas A&M, told Medical News Today, “As we age, we cannot switch quickly from one mode of metabolism (e.g., burning fat while we sleep) to another (e.g., burning carbs when we wake up). Quick transitions are necessary to meet our body’s on-demand needs.” Michelle Routhenstein, MS, RD, CDCES, preventive cardiology dietitian at EntirelyNourished.com, who was not involved in the study, explained, “During the day when active, the body primarily uses carbohydrates for energy, with higher insulin levels facilitating glucose uptake. At night, insulin sensitivity decreases, shifting metabolism toward using stored fat, as the body’s energy needs are lower, and growth hormone levels increase.” “As we age,” said Polymenis, “our bodies become less adept at adjusting their fuel source in response to changing needs, which can affect overall health and energy levels.”
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im too lazy to read the article but is this something to do with the form of folate they are giving (folic acid), or are they measuring food folate? aren't there issues with folic acid supplements building up in the blood and not being absorbed properly? because there are studies also showing in certain people with a gene type that cant metabolize the synthetic folic acid properly that it actually harms them to supplement it. and that if they take other forms like they methyl folate or folinic acid it doesnt seem to harm them.
anyways, whenever i eat cooked greens after awhile of not having them my hair gets extremely nice.
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I knew when they wanted to mandate supplemental folic acid in flour in the UK that it was potentially harmful and that I should be wary.
Governments are not very good at concealing their hands, are they?
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@Bling5
Yes me too, it seems to make my skin and hair shine
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@haidut A lot of folate in fruit though? If we accept the premise that fruit is the holy grail of food, what do we make of folate being anti-metabolic?
What if folate interacts with lifestyle, meaning you must be performing pro-anabolic and pro-synaptic activities to utilize it properly for cell formation?
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Hello, Jorge (or your bot).
That these vitamins increase the risk of cancer complications is not a reason to avoid supplementation, but to be more cautious with them.
One suggestion was to offer B-vitamins in separate products, something like:
- Mitochondrial function and toxicity: role of the B vitamin family on mitochondrial energy metabolism
- Mitochondrial function and toxicity: role of B vitamins on the one-carbon transfer pathways
But it's challenging to have a clear separation of vitamins because of interrelationships. Pyridoxin was excluded from their 'energy metabolism' group, but it's directly involved in glycogen use and the transaminases to prepare amino acids for oxidation. Biotin was included, but associated with anabolic functions, and one of the catabolic pathways would be dependent on the vilified (adenosyl)cobalamin. If all came down to an energy problem, the nucleotides of the energy-releasing coenzymes involve folate in their syntheses.
Cancer Cells Tune the Signaling Pathways to Empower de Novo Synthesis of Nucleotides
Growth-promoting substances don't just fuel cancer, they're also needed for cell and tissue regeneration.
Supplementation is discouraged for folate, cobalamin, and choline (or betaine). We know that the message is reaching a community that doesn't consume a lot of leaves (foliage→folate), nor legumes. The availability of folate in oranges is arguably lower than expected.
Tipping the reliance in favor of folate-cobalamin over choline might yield extra glycine, that can be formed for every folate cycled. The simultaneous restriction of these vitamins, along with a predisposition to their insufficiency, malabsorption syndromes, and the adoption of a diet low in methionine doesn't seem promising.
Do we have indications that the population is adequate in the anabolic vitamins and can afford a restriction? Because the typical consumption and positive reactions to supplementation suggest otherwise.
Not only a deficiency of any vitamin tends to predispose to cancer, but cancer is not the only disease to worry about. Cardiovascular problems and infections are major threats.
Digestion weakens in advanced age and disease, making it helpful to have available these vitamins in purified form. The issue here is that you're leaving for other vendors to do the dirty job of guaranteeing adequacy in a considerable number of people that would benefit from the carcinogenic nutrients.
