Folic Acid – Appetite Stimulant & Hunger Dysregulator. The nutrient with a double-edged sword.

Have you ever woken up in the middle of the night, REALLY hungry?

I mean SO hungry you’d eat anything in sight to quell the hunger? And thought, why I am so hungry!?!? What's going on? I don't get it. I ate well during the day, so this doesn't make sense.

Or perhaps experienced unrelenting hunger during the day that resumes itself shortly after eating?

Well, I have – and this sort of thing went on for years. Even when I ate well during the day, I would wake up, and be in this unexplainable state of intense, and what felt like “uncontrollable hunger.” Rather disconcerting to say the least.

It was really puzzling to me because when I went to bed, my intent was to sleep uninterrupted for a solid 6-8 hours – and the kind of hunger I was experiencing transcended all logic and reason. As someone who has spent the greater part of my life studying biochemistry and nutrition, it just didn't make "sense – and seemed to be in the “hormonal” realm of hunger – which really turns things up a notch as I will reveal in a second.

So, let’s proceed.

Some people would say, oh, you just have a fast metabolism – which, I did, but I hadn’t experienced anything like this in the decade or so before, so that wasn’t it. Or, maybe you’re just not eating enough during the day, which is why you’re waking up hungry? That wasn't it either. Something wasn't right (biochemically speaking), and I knew it.

What I didn’t know at the time – was that the vitamin supplements I was taking were the culprit. More specifically, the high amounts of synthetic folic acid they contained.

I was getting sometimes several times the RDA of 400 mcg in folic acid every day (from my multi-vitamin, breakfast and protein bars), and unbeknownst to me, this was having a HUGE effect on my appetite, hunger, and sleep.

The Truth About Folic Acid

Almost 20 years later, what I now know is this:

Folic acid is a powerful appetite stimulant, especially in higher doses (>400-600 mcg/day). If an individual is deficient in folic acid, the first thing that goes is their appetite. Here’s the thing, we do need folic acid, but for most people only in very small amounts for optimal functioning.

The amounts found in nature are nowhere close to those seen in multi-vitamins and processed foods. It is my belief – from hundreds of hours of research on this topic, and my own experience with folic acid though the years – as a nation we are overdosing on folic acid.

And the result is, a constantly hungry nation of people, looking to relieve their hunger in whatever sources are conveniently available to them, which often means fast-food or processed foods for millions of Americans – often “fortified” with additional synthetic folic acid – to further fan the flame of hunger. For many, it’s a vicious cycle that will not stop until you significantly reduce your intake of this synthetic nutrient.

If your brain tells you that you are starving, and your normal hunger mechanism has in effect – been “derailed” or dysregulated, you’ll darn near eat just about anything to relieve that hunger.

And, that is EXACTLY what many people do when experiencing “hormonal hunger” (more about that below).

Am I saying, this is the reason for the obesity epidemic in our nation? NO, but I do believe it could be a VERY strong contributing factor to what is simply regarded as “uncontrollable hunger” or “compulsive eating” – and why many people may feel a “compulsion” to eat foods that are not the best for them.

Folic acid and the Hunger Regulating Hormone Ghrelin

In the last decade, there has been a wealth of information published on this subject. Two of the most studied neuro-regulatory hormones are leptin and ghrelin, which have opposing effects on hunger and satiation.

It is well-documented that vitamins, as “metabolic activators”, influence the neurochemicals and hormones produced in our brain and nervous system. I’ve known for some time that folic acid is an appetite stimulant and activates our “hunger mechanism” – the question I had was, HOW did such small amounts of this seemingly innocuous and beneficial nutrient accomplish this?

What was the mechanism? …or downstream mediators (e.g. hormones, neurotransmitters, etc) that were facilitating folic acid’s powerful effects?

What Scientific Research Has Revealed

In a paper published in the journal, Endocrinology (2000), British Researcher, AM Wren found that the hormone “ghrelin stimulates food intake and growth hormone secretion” in subjects tested [1].

Seven years later, medical researcher M.D. Klok at VU University Medical Center in Amsterdam, published a 2007 paper looking at the role of “leptin and ghrelin in the regulation of food intake and body weight in humans”, and wrote the following:

Leptin is a mediator of long-term regulation of energy balance, suppressing food intake and thereby inducing weight loss. Ghrelin on the other hand is a fast-acting hormone, seemingly playing a role in meal initiation. As a growing number of people suffer from obesity, understanding the mechanisms by which various hormones and neurotransmitters have influence on energy balance has been a subject of intensive research. It is now established that obese patients are leptin-resistant" [2].

We know that hormones can have a powerful effect on our entire biology – including our mood, emotional state, strength, confidence, libido, and now appetite.

And guess what influences the production and release of these hormones?

That’s right, nutrients such as folic acid! So, on a hormonal level, is there a link between the appetite stimulating hormone, ghrelin – and folic acid?

Most definitely.

In fact, in a 2007 paper published in the FASEB Journal, Yuzuriha states, “Here we demonstrate that two principal GI hormones, PYY and orexigenic ghrelin, affect neural tube development” [3].

It is well-known that folic acid also has a powerful effect on neural tube development, and now we know, ghrelin – a hormone better known for its appetite stimulating effects, does as well.

Very interesting, to say the least.

So, what’s the relationship between folic acid (a vitamin) and ghrelin (a neurohormone)?

What I’ve discovered is – that folic acid and ghrelin are intimately related.

It’s not much of a leap to postulate that folic acid (as a metabolic activator, methyl donor) may promote ghrelin activity and release, which is perhaps why they BOTH function as appetite-stimulants and BOTH have a powerful influence on neural tube development and neuronal function.

In 2010, in the American Journal of Pathology, the authors found just that - that a methyl donor deficiency (folic acid is a methyl donor) resulted in “ghrelin dysfunction” and reduced ghrelin release [4]. This study offers strong supportive evidence that folic acid has a stimulatory effect on ghrelin activity, and that the two are directly related, and parallel one another.

To me, this explains why, on a very fundamental level, how folic acid acts as an appetite stimulant.

Folic acid ----> ↑ Ghrelin (neurohormone) ----> ↑ appetite

The Bottom-line

Ghrelin is a powerful hormone that increases appetite and feeding in both animals and humans, and methyl donors such as folic acid modulate and promote its activity.

So, if you’re eating a lot of processed foods on a regular basis – deficient in a variety of trace nutrients that your body is literally starving for – but ALSO fortified with high amounts of synthetic folic acid (which stimulates ghrelin activity) – it’s TRULY a double-whammy. It’s no wonder that you’re still hungry 30 minutes after you’ve just eaten. From a biochemical standpoint, it makes perfect sense.

Now, the answer is not avoiding all folate or folic acid. It’s avoiding high amounts of “synthetic” folic acid. Depending on your sensitivity that could mean anything over 400 mcg per day could be problematic, or if you're more sensitive, as little as 100-200 mcg could be enough to significantly effect your ghrelin-hunger mechanism – and promote night-time eating (waking up "starving" for food) and other compulsive eating behaviors.

For most people eating a diet rich in organic fruits, vegetables, organic eggs, grass-fed meats, fish, and leafy greens will provide all of this nutrient that your body needs to stay strong and healthy.

Folate vs Folic Acid

Folate is found naturally in plants and animal products, and is the “electron-rich”, active, reduced form of the vitamin.

Folic acid is not found in nature, and is the “electron-deficient”, inactive, synthetic form of the nutrient.

Synthetic folic acid is something I now personally minimize.

When I say “minimize”, I mean not going above 400 mcg per day of folic acid in all my supplements and food sources.

This level will vary with the individual, and some people are simply more sensitive to certain things than others due to differences in biochemistry, body weight, and metabolism. For example, women of low body weight (110 lbs or less) – may find that even 400 mcg per day, say in a multivitamin could be too much for them, and produce a significant or uncomfortable increase in hunger.

I prefer not to be hungry all the time, and it’s just something you want to be aware of, especially if you’re trying to lose weight – or like me, simply desire an appetite more in sync with nature and one’s natural biorhythms.