Steve Gibson's Healthy Sleep Formula (HSF)
Bedtime use of the six common dietary supplements shown above has successfully resolved chronic long-term insomnia for many people who have tried it. Because we are all different, no single solution will work for everyone. And some people have reported, with great disappointment, “it didn't do anything.” But a significant majority of people are reporting the first non-prescription relief of their insomnia—ever.

Though its development focus has been to resolve premature waking, which is clinically termed either “wake after sleep onset” (WASO) or “sleep maintenance insomnia” (SMI), The Formula may also be taken 60 minutes before bed to assist with “sleep initiation insomnia” (SII). You might also try just taking one extra l-theanine tablet 60 minutes before bed since that will tend to facilitate the more immediate functioning of the whole formula later.

Yes . . . and perhaps a few more:
This is a very gentle formula. Five of its six ingredients are already present in everyone. The remaining ingredient (l-theanine) is the most abundant amino acid in green tea. Each ingredient plays a distinct role and interacts synergistically with several others. With the exception of removing melatonin (see below) all attempts to simplify or reduce the formula have failed, whereas this six-pack has worked with very high reliability in many different people. Mounting evidence suggests that if you will give it a try just once you'll likely be sold.

Note that this formula is not designed or expected to prevent mid-sleep awakening due to bladder urgency, acid reflux, or other nocturnal disturbances. It was designed to make those awakenings brief and to allow its user to return quickly to sleep.

This six-supplement “cocktail” or “stack” is called the Healthy Sleep Formula (HSF) because its ingredients would individually promote health (stress reduction, reduced blood pressure, neural protection, cognitive and memory improvement) even if their combined effect wasn't also to induce sound sleep, which is also extremely healthful.

Dosage
“One of each” is the minimum strength for this formula. Experimentation with higher dosages may be needed if one of each is insufficient. In that case you should jump to two of each except for the melatonin, since 1mg of time-release melatonin should always be sufficient. People who are unfamiliar with dietary supplementation may be unaware that dosages are largely arbitrary. (Note how round all of the dose numbers are, below.) With the exception of the melatonin, you may be very free with larger dosages of any or all components of this formula. They are benign in any reasonable quantity.

You might find that one-of-each works initially while you are in sleep debt, but that two-of-each-except-melatonin may be required to keep you asleep all night once you are fully caught up on sleep. This is expected.

You may not need the melatonin: The Formula's low (1mg) dose of melatonin serves as a “sleep catalyst” which is all that's needed once the other amino acids and the serine phosphate have deeply calmed your brain and body. Our brain's endogenous melatonin production falls off rapidly as we age, but at varying rates and degrees. (Our pineal gland, which synthesizes our brain's melatonin, residing in the deep center of our brain, actually calcifies as we age!) If you don't need melatonin because your brain is making its own, it's better to let it do that for as long as it will. So try the whole formula for a week or two, then choose a night when you can afford for it to fail and omit the melatonin to determine whether it's necessary. If not, then by all means skip it.

The HSF Ingredients  (with Amazon & Swanson purchase links)
Please see the ingredient-by-ingredient details below for the functional role of each of the formula's ingredients. The following provides a purchasing and brief overview.

• Phosphatidylserine
  Phosphatidylserine (PS) is already present throughout our body as the majority phospholipid molecule forming the membranes (walls) of our cells. Studies of the cognitive effects of supplemental phosphatidylserine have repeatedly demonstrated improved test taking performance, reversal (by up to 12 years) of age-related memory decline, and much more. (See the PDF linked below for more about why supplementing with PS is health promoting.) However, it is PS's powerful cortisol-reducing benefit that makes it a crucial component of the HSF. Cortisol is regulated by our brain's hypothalamus and pituitary. They both contain cortisol receptors which sense the level of cortisol in our blood to determine whether to ask our adrenal glands to produce more or less. Phosphatidylserine reduces cortisol by restoring the lost sensitivity of those receptors. As our brain becomes better able to sense the cortisol that is already present, it requests less from our adrenal glands. Since elevated and dysregulated cortisol is a primary cause of insomnia, phosphatidylserine can contribute significantly to the success of the HSF. Phosphatidylserine has also been shown to facilitate cerebral uptake of GABA, which otherwise has difficulty passing through the blood-brain barrier.
  Geeky details: (Please feel free to ignore this. This is the sort of applied health biology that excites me, but I know it's not for everyone . . . though, come to think of it, it might put you right to sleep!) A single phosphatidylserine molecule is even larger than its name. It consists of a chain of interconnected molecules: At the head is a molecule of serine which is connected to a molecule of phosphate, which is in turn connected to a molecule of glycerol to which are attached two very large and long fatty acid tails. Our bodies already have an endless supply of fatty acids and glycerol. It's the serine phosphate (aka phosphorylated serine) which is rare and metabolically expensive for our bodies to synthesize. The functional success of the original (now discontinued) Seriphos formulation demonstrated that our bodies do not need the whole, large and expensive phosphatidylserine molecule. If we are provided with just the rare serine phosphate head group, our bodies will readily build the rest from there, attaching the glycerol and fatty acid tails. At this moment in the summer of 2016, the world does not appear to have a source of serine phosphate. So the HSF is currently being forced to use the (unnecessarily whole) phosphatidylserine molecule.
  
  The path of anything we ingest runs from our intestines, which interface the outside world to our insides, though our hepatic (liver) portal vein, through our liver, and then into our general circulation. In other words, by design, our liver gets the first crack at anything we ingest before those nutrients (or drugs or supplements) get into our bodies. Drug designers refer to this as “the first pass problem” because the liver is our body's primary chemical factory. It is filled with enzymes which transmute one chemical into another . . . and many otherwise useful drugs are unable to survive their journey. This is relevant to us, because our livers contain a lot of an enzyme known as Phosphatidylserine Decarboxylase (PSD) which aggressively converts phosphatidylserine into a related, but very different, phospholipid: phosphatidylethanolamine. (There will be no test on any of this.) The point is, not all of the expensive phosphatidylserine we ingest makes it through our liver and into our primary circulation where we want it. But by increasing the concentration of phosphatidylethanolamine we can suppress our liver's interest in making more. The original Seriphos was so effective because it wisely included some ethanolamine phosphate which caused our livers to leave the serine phosphate intact. But that that's also why you might want to try taking any Enerphos you might have alongside phosphatidylserine. Enerphos is less effective than Seriphos because it contains more ethanolamine and less serine. But that makes it useful for suppressing the hepatic conversion of the phosphatidylserine we want into the phosphatidylethanolamine we don't need.
  Before you repurchase phosphatidylserine, check back here to see whether a source of much less expensive and even more potent serine phosphate has been found.
  • Note that Swanson Vitamins offers their triple strength 300mg phosphatidylserine in both softgel and dry capsule forms. They are the same price and functionally equivalent. So if either sells out the other can be substituted. I selected the dry capsule because it is smaller.
  • If you can't sleep and want to learn more about phosphatidylserine, here's a terrific PDF research summary.
• GABA
  GABA is a convenient abbreviation for Gamma-AminoButyric Acid. It is one of our central nervous system's primary inhibitory neurotransmitters. (Glycine and Serotonin are the other two.) The Internet is oozing with misinformation about the value of supplemental GABA. This is driven by the fact that studies have shown it is unable to pass through our brain's blood brain barrier. Anyone who believes that GABA has no effect hasn't bothered to try it. It may not be necessary for GABA to get into our brain for it to have profound relaxing effects on our enteric nervous system, vagus nerve, non-barriered portions of our hypothalamus, pituitary, and adrenal glands. However, two other ingredients of the HSF have been shown to promote GABA's uptake across the blood brain barrier:
  • Co-administration of phosphatidylserine with GABA has been shown to significantly increase brain GABA uptake and GABA concentrations in the cerebral spinal fluid.
  • L-Theanine stimulates the production of nitric oxide in endothelial (arterial lining) cells. This is not only heart-healthy in itself, but nitric oxide has been shown to promote the passage of GABA through the blood brain barrier by increasing the barrier's permeability to GABA, thus further encouraging GABA's relaxing effects.
  This demonstrates the synergy that exists among the HSF's individual components. As long as GABA is purchased from a reputable supplier, any GABA can be used. Now Foods produces a 750mg capsule which allows fewer to be used.
• L-Theanine
  L-Theanine has been widely studied because it is not only the majority amino acid in green and black tea, but tea contains more l-theanine than all of tea's other amino acids combined. It enters our brain through a saturable active transport (known as the leucine-preferring transport) which it shares with several other dietary amino acids. (Which suggests that it will be less effective when taken on a full stomach due to competition with other much more abundant dietary amino acids.) Though l-theanine is not endogenous in humans, green tea is the most consumed beverage in the world, second only to water. Its safety has therefore been long and well established. The HSF employs l-theanine for its multiple profoundly relaxing functions. Many studies have shown that l-theanine ingestion results in an increase in levels of cerebral GABA, glycine and dopamine and a reduction in glutamate and glutamine. GABA and glycine are both inhibitory neurotransmitters which powerfully encourage sleep, and dopamine makes us feel good (not very scientific, I know). Glutamate/glutamine are the brain's primary excitatory compounds, so less of them is better for sleep. L-theanine tends to block the uptake of glutamate & glutamine into our brain's neural and glial (non-neural) cells. This raises our brain's extracellular concentrations of those stimulants. And since their concentration is tightly regulated, that l-theanine-induced excess is driven back through the blood brain barrier, out of our brain and into our circulation for use elsewhere.
  
  Why the Source Naturals solid tablet formulation? Any formula designed to keep us asleep through the night probably needs to remain effective for most of that duration. The challenge is that as our circulatory system pushes our blood through our liver and kidneys, each pass gradually removes uncommon substances from our blood, even if we would prefer that they remain around. Biochemists refer to “the metabolic fate of theanine” and have determined that our kidneys contain the glutaminase enzyme which hydrolyzes theanine, converting it into glutamic acid and ethylamine (aka “other stuff”). The nature of this removal is that a percentage of the total is removed. This means that the more there is to remove, the more is removed. Standard cellulose capsules release their entire dosage all at once when the capsule dissolves. This results in a sudden increase in the concentration of the supplement, and a corresponding high rate of removal. Since l-theanine's passage into our brain across the blood brain barrier is rate-limited through a so-called saturable transport, most of a high-concentration pulse would not be absorbed before it was removed from our blood stream by our kidneys. Source Naturals (a well-regarded supplement supplier) l-theanine tablet dissolves slowly in our intestinal tract over the course of many hours. This produces a continuous low-dosage trickle of l-theanine into our blood stream and therefore a much lower rate of renal removal. The result is that the tablet remains effective throughout the night, and that much more of the tablet's total l-theanine is able to cross into our brain during that time. If you were previously using any other form or brand of l-theanine be prepared to experience a significant difference.
  
  The Source Naturals l-theanine tablet is not sold or marked as “extended release.” However, its ingredients show that it is bound together with cellulose gum which dramatically retards the tablet's disintegration in the stomach and small intestine. So, while Source Naturals makes no specific slow-release claims, they deliberately designed it for slow release, and experience demonstrates that it is effectively extended release.
  
  One other quick note: Although glycine (another critical component of the HSF) itself is readily absorbed by our brains, it appears that the leucine-preferring transport, which moves l-theanine into our brains, is actively inhibited by high concentrations of glycine. Therefore, if both l-theanine and glycine were released immediately, l-theanine would lose the contest. Allowing glycine to quickly spike and be absorbed by our brain quickly, while l-theanine spends the rest of the night trickling in, allows us to get much more benefit from the l-theanine.
• Glycine
  Glycine is another inhibitory neurotransmitter. Unlike GABA, glycine readily passes through our brain's blood brain barrier using linear, non-saturating, dose-dependent diffusion. It is the smallest possible amino acid, is widely present in diet, and can be synthesized in our bodies as needed. Therefore, it is extremely benign and may safely be used at higher doses. To sleep well, our body's core temperature must be reduced, and in addition to calming our brain, glycine significantly induces a reduction in core body temperature. As with GABA, glycine is widely available and any glycine purchased from a reputable supplier may be used.
  TIP: If you are a person who uses sweetener in beverages you may be avoiding sugar while being uncomfortable with the use of unhealthy synthetic non-sugar sweeteners. So you might try opening a 1g capsule of glycine (or two) and adding it instead. Glycine is sweet and actively good for you. And a 1g capsule provides just 4 calories of energy. (You could probably just drop the whole capsule into a hot beverage since it would dissolve almost immediately.)
• Taurine
  Taurine is highly beneficial to health (see below) and usually exerts a gentle brain calming action that is intended to aid our Healthy Sleep Formula. However, taurine appears to be stimulating for some people, which would be the reverse of what we want. Some people have also reported a diuretic effect. Since taking a diuretic agent at night can increase the need for nocturnal urination, this can interrupt restful sleep. However, both of these sleep-disrupting effects have turned out to be transient, resolving and disappearing after several days to a week. Therefore, if the HSF with taurine doesn't initially work for you, or if your sleep is more interrupted than normal when using taurine, try moving taurine to the morning. This will allow your body to adapt to this new supplement without it keeping you awake or waking you for trips to the bathroom. After a week or two, try moving taurine back into the HSF before bed for its significant benefits there.
  Taurine was only recently identified as a neurotransmitter when neural receptors specific to taurine were finally identified. And no one is yet sure what those receptors do. What is known for our purposes is that, among its many other positive health benefits, taurine is a strong “agonist” of our brain's GABA and glycine receptors. An “agonist” is the reverse of an “antagonist”, thus taurine encourages the action of these receptors, and the GABA and glycine receptors are inhibitory: They calm our brain by exerting an inhibitory action on neural firing. What's more, taurine increases the expression of an enzyme known as “glutamic acid decarboxylase” (GAD for short). This enzyme converts glutamate into GABA. So more taurine means more GABA and less glutamate. It's a win all around.
  
  There is so much more to say about taurine's many health benefits that I plan to give it a page of its own. But until that page is written, here are a few bullet points:
  • The majority free amino acid in humans. There's more in us than any other free amino. (Unlike most amino acids, taurine is not used to build proteins, so it's free to exert its various effect.)
  • Reduces the “bad” (LDL and VLDL) cholesterol through several mechanisms.
  • Reduces blood pressure. ← (This could be a good or bad thing, depending.)
  • Functions as an anti-inflammatory antioxidant.
  • Induces or encourages weight loss.
  • Anti-diabetic through lowering blood glucose and restoring insulin sensitivity.
  • Enhances exercise performance. (Which is why it's an ingredient of energy drinks.)
  • Strong retinal antioxidant.
  • May help some people to reduce and even reverse tinnitus (ringing in the ears).
  • Helps with indigestion and symptoms of heartburn.
  • Appears to protect our livers from damage from abuse.
  • And yet, it is the least expensive of any of the HSF supplements!
  I'm aware that these claims are extreme. Rather than backing them up on this page, here are some links to the research so that you can explore further for yourself until I'm able to get the taurine page written: Therapeutic Applications of Taurine provides a useful overview. Additionally: PDF PDF PDF PDF PDF PDF PDF PDF PDF.
  
  If you wonder why the world doesn't know more about this amazingly beneficial and inexpensive supplement (or, for that matter, vitamins C, D, magnesium, etc.) it is simply because these naturally occurring substances cannot be patented. This, in turn, prevents them from being sold at extortionary prices for massive profits. This means that expensive clinical studies are not underwritten, and those interested in finding our own path are truly on our own.
• Melatonin
  This 1mg time-release melatonin formulation also contains 10mg of vitamin B6. It is included because B6 is a required cofactor for the synthesis of most neurotransmitters. So adding a bit of B6 helps to further us toward our goal. However, some people find vitamin B6 to be agitating and avoid any supplementation. If you are such a person, Life Extension produces a 750 mcg (0.75 mg) 6-hour timed release melatonin which would allow you to avoid any added B6. (iHerb)
  Most people who suffer from poor sleep know of melatonin. It is the “darkness hormone” produced by our pineal gland in the absence of light at the blue end of the spectrum. The trouble is, endogenous melatonin production falls off rapidly as we age, and in many people lowered melatonin levels fail to reliably induce sleep. In our experiments we found that sufficiently high doses of all of the other HSF ingredients could induce a state of truly profound calm and relaxation. But without just a hint of supplemental melatonin to catalyze sleep, we were not tipped over the ledge into unconsciousness. In this context, melatonin functions as a sleep catalyst. By itself it is insufficient to induce sleep. This explains why no amount can sedate an over stimulated person into sleep. But if its user is otherwise profoundly relaxed, melatonin can make all the difference.
  
  The other key is deliberate extended time release. This is crucial. Standard supplemental melatonin will be metabolized (broken down) and cleared from the blood stream within a few hours of ingestion. So if a person wishes to be kept asleep all night, a constant trickle of new melatonin must be provided.
  
  Finally, in the case of melatonin, more is not necessarily better. Melatonin is a potent hormone which is normally present in microgram (millionths of gram) concentrations. This is why the HSF only uses 1mg of time-release melatonin. Tens of milligrams is a supra-physiologic dose and is serious overkill.
  
  We recommend this Natrol brand of 1mg time release melatonin. If you choose some other brand, please be sure it is 8-hour extended release.

Pleasant Dreams!