This amino acid can help with insomnia, anxiety and depression. Dr. Wright has good info on tryptophan. Ray peat warns against tryptophan because it is converted into serotonin which causes inflammation at high dosages.
2014-06-01. From the books of dr. Wright I learned about tryptophan as an anti depressant, anti anxiety substance and sleep aid. I’ve been using it for about two years now and it has always helped me greatly and fast. Then I read Ray Peat about tryptophan.
Both tryptophan and cysteine inhibit thyroid function and mitochondrial energy production, and have other effects that decrease the ability to withstand stress. Tryptophan is the precursor to serotonin, which causes inflammation, immunodepression, and generally the same changes seen in aging. Histidine is another amino acid precursor to a mediator of inflammation, histamine; would the restriction of histidine in the diet have a longevity promoting effect, too?
I do suffer from inflammation a lot and always. So I thought: maybe that’s the tryptophan and muscle meats I’m eating? So I started supplementing with gelatin some weeks ago. I take two tablespoons daily: one the morning and one right before bed. It really didn’t make me feel any different. Although it is true: I am needing less thyroid hormone (I was still on 1 grain Thiroyd daily): I hadn’t been taking mine in a few days already. But then, it’s getting to be summer, so that might have something to do with needing less thyroid also.
Then, about two weeks ago, I started getting weepy. Little things just set me off. I thought I was just tired: it was a busy time at work and I wasn’t sleeping too well either (hyperthyroid). This weekend though, it got full blown anxiety, depression and insomnia. So I got to thinking what was going on. As I was cleaning I saw the container with tryptophan and was about to stow that away because Ray Peat really makes such a convincing argument. But then I thought: I’d rather have inflammation than this lousy feeling, so I took some (together with niacinamide and some carbs). After one hour the depression and anxiety just lifted. Also I slept like a baby last night.
So, what’s the deal here?
If I had to choose between low tryptophan with better thyroid function and energy production on the one hand OR taking tryptophan and being happy and having to take 1 grain of Thiroyd and cranking my energy production up some other way on the other, the choice would be easy: I want to be happy. To me, there’s nothing worse than feeling like crap. I can tolerate a lot of fatigue or pain, but depression and anxiety just make life unlivable for me.
I took quite a bit of tryptophan yesterday and this morning woke early with massive inflammation: jaw behind left upper molar was inflamed, lymph under lower jaw on left side was full of puss, my wrists and ankles throbbed and were warm, everything seemed to hurt. So I probably overdid it a little 🙂 (I always do that, I can’t help myself).
I is kind of nice to know though that I can tweak this myself: I can choose between high or low tryptophan by either tryptophan or gelatin supplementation. The gelatin will (relatively) lower the tryptophan and also, because it holds the large amino acids, will impede its progress.
Needless to say I took gelatin and no tryptophan this morning. Hope that I feel better later in the day…
At the end of the spring of this year I developed severe depression. This turned out be caused by a zinc deficiency. My B6 was low too. So I started taking both in large dosages to get out from that depression. Fortunately, it did get better. Later though, about a week ago, depression again started. This time B3 as niacinamide, coupled with tryptophan helped really well. Turns out that large dosages of B6, unaposed by niacinamide, convert tryptophan really fast so that it is depleted, leading to depression.
Then, read (the point is being made on this 2nd page) Part II: http://m.lef.org/magazine/mag2008/apr2008_Why-Aging-People-Become-Depressed-Fatigued-And-Overweight_02.htm
There are two enzymes that lower tryptophan: TDO and IDO. TDO rises as tryptophan rises above the level needed by the body (a good thing). IDO is always there and rises as inflammation rises (not a good thing).
Giving tryptophan with an inhibitor of the TDO enzyme would enable lower doses of tryptophan to be used. B6 is mentioned as a possible inhibitor.
Inflammation raises IDO levels. This in turn lowers tryptophan levels.
You can’t compensate by eating more tryptophan, because that will trigger the release of more TDO.
Niacinamide can stop the degredation of tryptophan. Lysine helps prevent oxidation of tryptophan. Curcumin inhibits inflammation and by doing so may inhibit IDO. Anything that brings down inflammation will in this sense lower IDO.
Cofactors that facilitate the conversion of tryptophan to serotonin in the brain are vitamin B6, magnesium, and vitamin C.
He talks about excess tryptophan. Well, that’s the whole issue here, isn’t it? What is too much? For me, apparently, taking gelatin lowers tryptophan too much.
From part I: More clinically relevant, however, is that serotonin levels are enhanced by carbohydrate ingestion. The reason is that the high amount of insulin released in response to carbohydrate ingestion accelerates the serum removal of valine, leucine, and isoleucine that compete against tryptophan for transport into the brain. Similarly, a higher percentage of protein in the diet slows serotonin elevation (by providing competing amino acids for the blood-brain barrier).34,35
B6 as p5p helps tryptophan from being broken down and removes metabolites that block entry into the brain.
From part I: Giving tryptophan with an inhibitor of the TDO enzyme would enable lower doses of tryptophan to be used. In the rat, high doses of pyridoxine (vitamin B6) can inhibit tryptophan catabolism in the liver and increase uptake of tryptophan into the brain. While the effect of high doses of pyridoxine on plasma tryptophan has not been studied in humans, pyridoxine should be given with tryptophan for another reason. When tryptophan was given to normal subjects for a week, levels of tryptophan metabolites in the plasma increased indicating that tryptophan was being broken down. This effect could be attenuated by pyridoxine (pyridoxine assists the breakdown of the tryptophan metabolite kynurenine, which can compete with tryptophan for uptake into the brain), suggesting that chronic tryptophan treatment increases pyridoxine requirements.
Read the whole article, it’s very good!
you should have been prescribed the pyridoxal 5 phosphate with the tryptophan from day one. All amino acids should be accompanied by p5p. Tryptophan is used for someone with depression because it increases serotonin levels. Serotonin is a neurotransmitter in the brain that is responsible for regulating our mood states and is often depleted in people with depression. However, tryptophan cannot be converted to serotonin without sufficient levels of p5p, and many people are deficient in p5p. So that could be another reason you had the response you had. So, adding the p5p to your regimen may solve your problem.
See Ray Peat for reasons not to overdo the tryptophan. Take as much as you need to feel calm and collected and have a good nights sleep. Just don’t overdo it.
If you need much, spread it throughout the day. Take one dose before going to bed, because it will make you sleep like a baby.
Take your tryptophan away from other amino acids. Especially tyrosine + phenylalanine + leucine + isoleucine + valine.
Make sure to get enough lysine (an amino acid), you can take lysine with the tryptophan, I do so and I have no problems with it.
Eat some carbohydrates with your tryptophan. See absorption.
Take B6 (as p5p), magnesium, vitamin C and niacinamide (this is a specific form of B3). Niacinamide will lower your need for tryptophan.
Try to reduce inflammation in your body, by:
- keeping your glutathione levels up
- taking curcumin
- taking vitamin C
- taking iodine
- eating coconut oil
- giving the body all the nutrients it needs
- NOT eating anything that induces inflammation:
- white flour
- muscle meat without fat and without vitamin A
- anything without (hardly) any nutritional value
- unsaturated oils
From part I:
There are three potential fates for L-tryptophan once ingested:
- Incorporation into body tissue proteins.
- Conversion into serotonin (and melatonin).
- Conversion into indoleamines, carbon dioxide, water, adenosine triphosphate (ATP), and niacin.21
There are two specific enzymes that can deprive the body of sufficient amounts of tryptophan. These enzymes are called L-tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO).
The liver enzyme TDO is induced when plasma concentrations of L-tryptophan exceed those needed for conversion into serotonin and/or protein. This enzyme oxidizes surplus L-tryptophan into carbon dioxide, water, and ATP.22,23
The other tryptophan-degrading enzyme IDO is more insidious because it can degrade L-tryptophan even when circulating levels of L-tryptophan are low.23,24
This enzyme has been found outside the liver on macrophages and dendritic cells and is increased in pro-inflammatory states, HIV infection, and normal aging.25-30
Once the TDO or IDO enzymes act on tryptophan, it is no longer available for conversion to serotonin or incorporation into protein. Consuming large amounts of oral L-tryptophan will not generate more serotonin because more TDO will be induced to deplete the tryptophan.
Tryptophan and its metabolite 5-hydroxytryptophan (5-HTP) are taken up into the brain across the blood-brain barrier by a transport system that is active towards all the large neutral amino acids.31 The affinity of the various amino acids for the carrier is such that there is competition between the large neutral amino acids for entry into brain. In fact, the best predictor of a given meal’s effect on brain tryptophan-serotonin levels is the serum ratio of tryptophan to the pool of large neutral amino acids.32
From part II:
How Aging Reduces Tryptophan-Serotonin Levels
As a result of normal aging, inflammatory cytokine levels increase. A little-known adverse effect is that inflammatory cytokines (such as tumor necrosis factor alpha and interferon alpha) cause induction of the tryptophan-degrading enzyme IDO (indoleamine 2,3-dioxygenase).
You might think that aging people could compensate for the tryptophan-degrading effects of IDO by consuming higher doses of tryptophan supplements. The problem is that in the presence of high blood levels of tryptophan, the other tryptophan-degrading enzyme TDO is also elevated.
So consuming large amounts of L-tryptophan (oral doses of 4,000 mg and greater) will not generate more serotonin because TDO will be induced. Yet if aging people fail to get more tryptophan into their bodies, brain serotonin levels will plummet because the higher IDO enzyme activity will degrade what little tryptophan remains in the blood.
Engineering Around This Problem
Fortunately, the new understanding of how tryptophan is degraded in aging humans provides a basis for engineering a natural solution around this epidemic problem.
First of all, we know from studies in patients with high levels of systemic inflammation that if sufficient niacinamide is given, the degradation of tryptophan in the body is significantly reduced.57,58 We also know that the amino acid lysine competes with tryptophan in the same oxidative degradation pathway. This means that in the presence of lysine, less tryptophan is oxidized.59
Tryptophan, however, can still be degraded by the IDO enzyme that increases as humans age. Nutrients such as curcumin inhibit interferon-induced nuclear factor-kappa-B and COX-2 expression and may limit the induction of IDO, thus making more tryptophan available for conversion to serotonin in the brain.60
It is thus possible for aging people to supplement with a modest dose of tryptophan (1,000-1,500 mg per day) and significantly decrease tryptophan oxidation/degradation, as long as lysine, niacinamide, and the proper cytokine-suppressing nutrients are taken with it to neutralize the effects of the IDO enzyme.
Cofactors that facilitate the conversion of tryptophan to serotonin in the brain are vitamin B6, magnesium, and vitamin C.60-62 These nutrients are already taken by most health-conscious people.
An important factor in the decision to supplement with L-tryptophan is its excellent tolerability and the lack of development of tolerance during long-term use. Furthermore, L-tryptophan does not cause difficulties when trying to wake up the next morning.63
The minimal dose of L-tryptophan for effective treatment of insomnia may be at least 1,000 mg, and repeat administration of L-tryptophan may be required for improvement in chronic, well-established, sleep-onset insomnia or insomnia characterized by both sleep-onset and sleep-maintenance abnormalities.63 Low doses of L-tryptophan (250 to 500 mg) may not offer a significant benefit on sleep latency.64 For those with insomnia who wish to try L-tryptophan, a strong initial dose (1,000 to 4,000 mg) is recommended for the first week, followed by a lower maintenance dose (500 mg to 1,000 mg).
Evening oral doses of tryptophan as low as 250 mg have been shown to improve sleep quality, although the typical dosage range for sleep disorders and depression is 1,000-3,000 mg daily. Safe and effective dosages for other disorders range from 500 mg to 4,000 mg/day, while doses around 3,500 mg/day have been used short term as a smoking cessation intervention.65
Tryptophan is oxidized in the liver by tryptophan-2,3-dioxygenase (TDO), an enzyme that is induced both by glucocorticoids and by large doses of tryptophan itself. The enzyme activity of TDO increases after tryptophan administration66 and results in a relatively short half-life of tryptophan remaining in the plasma.67 Thus, tryptophan is often given in divided daily doses instead of a single dose. A single dose of 3,000 mg is sufficient to keep human brain serotonin synthesis maximized for about eight to twelve hours.68 Giving three daily doses of 2,000 mg will probably keep the rate-limiting tryptophan hydroxylase enzyme in the brain fully saturated for most of each 24-hour period, meaning that brain serotonin levels would be maintained at a constant optimal level.
- Most of it is (over 90%) is in the gastrointestinal system regulating digestion.
- Regulation of pain perception. Low levels of serotonin increase pain perception. This can contribute to chronic pain such as in classic fibromyalgia.
- Regulates sleep through conversion to melatonin. Melatonin is our sleep hormone. It is low during the day, then goes up at night so we can fall asleep.
- It does not compete with other amino acids to cross the blood-brain barrier
- The conversion of tryptophan to 5 HTP is the rate-limiting step in the synthesis of serotonin; this means that this conversion is the weakest link in the production of serotonin. Therefore, 5 HTP supplementation represents a bypass of this step in the synthesis of the neurotransmitter
- Tryptophan is an amino acid that is also utilized in the production of other biochemicals while 5 HTP is solely committed to the synthesis of serotonin
- Tryptophan is more likely to be converted to serotonin in the liver than 5 HTP. This happens because 5 HTP faces no competition to cross into the brain, therefore, it is easily taken up. Tryptophan, on the hand, is easily converted to serotonin in the liver while it waits to cross the blood-brain barrier
- 5 HTP is obtained from plant sources while L-tryptophan is produced from bacterial fermentation; therefore, there is a lower chance of contamination in 5 HTP supplements (and thus, lower risk of EMS) than tryptophan supplement