Your Gut, Neurotransmitters, and Hormones


READERS SUMMARY:

1. HOW YOUR GUT BRAIN AND RESPONSE OF YOUR BRAIN ARE ALL TIED TOGETHER?
2. WHAT ARE THE 4 MAIN NEUROTRANSMITTERS?
3. WHAT DO THEY DO AND MEAN?
4. WHAT AFFECTS THEIR PRODUCTION?
5. HORMONES ARE THE BRAINS ENDOCRINE SECRETION THAT TELLS YOU HOW YOUR EPIGENETIC SWITCHES ARE SET.
6. HOW WE USE HORMONE STAUTS TO FIGURE OUT WHAT IS REALLY WRONG WITH YOU?

The next post in the series follows directly upon what we learned about the brain and ketogenic diets. Today we are going to mesh the brain gut axis and neurotransmitters so you can begin to understand how diet can modify your personality and your behavior. In severe cases it can also cause mental illness and eating disorders. In fact, if you have never heard of the GAPS diet you need to read a bit about it. Today I will lay out some of the biologic plausibility of how this occurs and some interesting clinical correlates to specific NT deficits from our diets. Everything in biology usually ties back to the brain at some point and this is very clear in NT biology. Neurotransmitters are involved in many neural circuits in the central and peripheral nervous system. They are also found in the autonomic nervous system and in the enteric neural circuits in our guts.

There are four main neurotransmitters (NT) in the brain and we will focus on them to make some general principles clear. They are Serotonin, Acetylcholine, GABA, and Dopamine. There are quite a few other neurotransmitters but I don’t want to overwhelm you the biochemistry of this class of molecules because it is quite complex and, at this point of the QUILT roll-out, not all that important.

All the neurotransmitters are made from amino acids from proteins except acetylcholine (Ach). Ach is made from dietary choline or recycled choline and acetyl groups from the Krebs cycle. All macronutrients are required to make all the parts of NT for proper function. No food group can be excluded and still expect to have proper NT function. Dietary neurotoxins like phytic acid, lectins, excess caffeine, nicotine, mineral depletion, vitamin depletion, and alcohol can affect NT production. Some are made entirely by the body. Some are converted by the biologic machinery we have. If we don’t have sufficient supply of certain substrate amino acids (AA) we may actually lack the substrate to construct NT for optimal function. This can lead to changes in mood or behavior when we alter fuel sources or change our diets.

Serotonin begins with the AA tryptophan. It requires B6, Mg, B12 and folate as co factors in production. B Vitamins are the major methyl donors in the production many NT so they are vital for brain function and development. If you fail to eat them or absorb them you can bet your ass that you will suffer from serious mental or neurologic issues at some point down the road. Tryptophan is the least common AA in our diets. It also happens to be the most difficult to absorb into the brain. This also complicates serotonin biochemistry. Tryptophan is found in fish, poultry, and dairy products but eating these products does not necessarily increase serotonin levels. The reason for this paradox is because other foods compete with tryptophan for absorption in the gut. It has to compete with other AA. In fact, another paradox of serotonin production is that is eating carbohydrates raises its level in the body faster than does eating a protein diet! The reason for this is that carbs stimulate insulin release and this insulin spike favors the absorption of tryptophan in the gut over other amino acids. So this is a reason why eating some carbs is important. Many zero-carbers make a huge error in not realizing this. This helps you understand why people who need serotonin tend to be stress eaters and eat more sweets and starches. Moreover, studies from MIT, Harvard and Oxford have shown that women on a high protein and low carb diet are more prone to low serotonin levels. In the paleo world this is called the “low carb flu.” This is easily overcome when you change your diet by using 5-HTP for about two weeks to adjust to your new diet. If the person was previously seriously serotonin depleted this could cause initial weight gain while dieting, severe cravings, binging, bulimia, and severe PMS. I have even seen a flare up of seasonal affective disorder myself. Men are 52% more effective in absorbing tryptophan than women too. Most serotonin is stored in the enterochromaffin cells of the gut lining (60%) and the balance is stored in the pineal gland of the brain. The gut is used as a storage site when to restore the brain when it is needed. Dietary carbs may play a big role in brain health. Dr. Judith Wurtman from MIT has published many articles linking low carb diets to deficiencies in serotonin and causing mood disturbances but there is some controversy about her theories. In fact, there appears to be a pronounced difference in gender. Women tend to make 30% less serotonin than men. Many believe this due to their lower growth hormone levels and higher leptin levels. Women maybe more susceptible to mood changes on low carb and high protein diets. This point is not set in stone.

Dopamine is made from the AA tyrosine. Eating a high protein diet promotes dopamine production. It is abundant in poultry, meat, dairy products, almonds and avocados. It’s why we formed our large brains from an evolutionary point of view. Dopamine is the NT of our newest part of our brain, the frontal lobe. The majority of tyrosine that does not get incorporated into proteins is catabolized for energy production. One other significant fate of tyrosine is conversion to the catecholamines (NE, and EP). The catecholamine neurotransmitters are dopamine, norepinephrine, and epinephrine used in stress response tracts. The NT production line uses methyl transfers at several steps to accomplish this and it should be clear now why B vitamins are critical to neurons. They are the substrates that donate these methyl groups to make the final neurotransmitters.

Dopamine levels in the brain directly correlate with voltage intensity on an EEG exam. An EEG is a test we neurosurgeons or neurologists use quite often to assess patients. For example, a mother who was an alcoholic during pregnancy causes epigenetic signaling in an unborn fetus and predicts an obesity pattern for the unborn child due to a dopamine deficit. Children who are born dopamine deficient tend to crave sweets to increase their brains voltage via their reward tracts but the food can never replenish the lost power. This is especially powerful when the hypothalamus never becomes sensitized to leptin by breastfeeding. Remember your mom’s colostrum contain her leptin that acts as a USB drive for your brain to be set. If your mom is leptin resistant or your mom does not breast feed you, your brain begins at a disadvantage at birth. It can still be overcome but most of the time it is not because of the use of baby foods with crap in it (similac and Gerber’s). Epigenomic programming for leptin resistance has been shown to heavily influence the future dopamine status in the brain reward centers of the brain. Leptin and dopamine are coupled in the brain at the hypothalamic level. When leptin is released from adipocytes and it is properly signaled in the hypothalamus it immediately decreases reward behaviors for food seeking and the person will stop eating much sooner. This is commonly seen in diets with high protein and fat contents especially at breakfast within thirty minutes of waking. People low in dopamine tend to crave caffeine to a great degree. Addictions of all types are associated with dopamine deficits and damage at the hypocretin neurons in the hypothalamus. The expected phenotype of someone with low dopamine levels is usually an adult with high cortisol levels and copious amounts of abdominal obesity and many neolithic diseases. Another interesting clinical correlate I have found is that in patients with dopamine deficiency are very deficient in the hormone substrate pregnenolone. This occurs at a very early age as well and is the major predictor of future hormonal imbalance in my practice. Adding it back to their diet tends to accelerate their weight loss. I believe this is because of the high levels of cortisol from the long term leptin resistance that underlies their obesity type in the hypothalamus.

Acetylcholine was the first neurotransmitter discovered and is the major neurotransmitter in the peripheral nervous system. Acetylcholine (Ach) is the NT that tends to control processing speed in the human brain. Brains high in Ach usually are razor sharp. This is the NT that is lost most severely in Alzheimer’s disease. It allows for quick reaction time and thinking. Ach production is tied to dietary fat intake especially cholesterol and saturated fats. The Acetyl CoA comes from metabolic breakdown products of glucose and fructose and the choline comes from phosphatidyl choline, the major phospholipid in the membranes of plants & animals (but not bacteria). The choline is absorbed directly across the blood brain barrier as I laid in my my recent post by astrocyte foot plates. Eggs and organ meats are rich in substrates for Ach production. Choline is found in high concentrations of both egg yolk and offal. It is in the B vitamin family. B5 is a co factor in its synthesis as well. Vitamin B5 enhances the ability of Arginine to stimulate the release of human Growth Hormone as well during slow wave sleep (hGH).
What can one expect clinically if you are deficient in Ach? Your ability to think will be slower. Memory lapses more common and you may notice more frequent trips to the restroom for bowel movements and urination. Sexual dysfunction also is more common. The phenotype of those with Ach deficits are that of a “worry wart”. Ironically, they never seem to care a lot for their own well being though. They tend to be nurturing and perfectionists with little initiative and quite inflexible. Ach deficiency is a real problem in menopause and andropause because the sex steroids are Ach stimulants. So as the sex steroids drop as we age, mental processing speeds slow. Ask any menopausal woman if this is not a common symptom. I know because my practice is filled with them. This is clearly seen as the “cognitive haze” as hormones fall in perimenopause and andropause. This has been occurring earlier in life in the USA due to the rise of diabetes and those with high cortisol levels. High cortisol levels lead to rapidly falling sex steroids and vitamin D levels due to pregnenolone steal syndrome. The falling vitamin D levels also appears to play a role in the development of autism spectrum disorders and autoimmune conditions. As cortisol rises, this worsens the ACh deficit and cognitive decline becomes more evident. Persistent cortisol elevation further destroys the gut surface and makes it more permeable to inflammation and this worsens the NT deficits over time. This becomes a serious positive feedback loop. Moreover, in the USA with a SAD we are seeing earlier onset perimenopause because of the combination of low fat diets and simultaneously declining sex steroid hormones from pregnenolone steal syndrome. The response of many physicians is to treat patients with anti-depressants medications but what they need is a return to a higher fat diet. I ask my older patients to eat 60-75% fat diets until they normalize. They all looked at me shocked based upon the CW they have heard until I explain WHY? There is a current epidemic of low vitamin D in the USA that is being recognized but not accurately treated with dietary modification. Adding dietary fats back can really change these biochemical processes and patients behavior quickly. Hormone levels are the best way to assess epigenomic switch settings. It tells us precisely how the brain is partitioning calories based upon its current deficits.

GABA is γ-Aminobutyric acid. GABA deficiency has been linked to anxiety disorders, panic attacks, addiction, Parkinson’s syndrome, cognitive impairment, insomnia, headaches, and seizure disorders like epilepsy. GABA is our natural “off” button to life. It is the NT of relaxation. GABA directly counter balances the stresses of life from dopamine and serotonin. GABA is made from glutamate, but not in the gut. GABA does not penetrate the blood-brain barrier; it is synthesized in the brain and spinal cord. It is synthesized from glutamate using the enzyme, L-glutamic acid decarboxylase and pyridoxal phosphate (which is the active form of vitamin B6) as a cofactor via a metabolic pathway called the GABA shunt. The way to increase GABA in the brain is by supplementing its precursors properly, namely Pyridoxal Phosphate, the active form of vitamin B6. B6 usually comes in animal proteins of the diet (sorry Vegans!). One of the key modulators of GABA is Taurine. Taurine, itself a powerful inhibitory neurotransmitter helps balance and control the effectiveness of GABA in the brain.
This brain process converts glutamate, the principal excitatory neurotransmitter, into the principal inhibitory neurotransmitter of the CNS, GABA. This inhibitory NT is involved in controlling brain rhythms and muscle tone. People deficient in GABA tend to eat quickly and often. They often struggle with portion control of their meals. They often taste their food when cooking and rarely miss any desserts. GABA has many varied biological affects in the brain. This occurs because of its unique organic chemistry. The chemical conformational flexibility of GABA is important for its biological function, as it has been found to bind to different receptors with different conformations. Many GABA analogues with pharmaceutical applications have more rigid structures in order to control the binding better but this affects their neurochemistry in vivo. In fact, this neurotransmitters’ biologic diversity of action is tied to its quantum chemical behavior. Yes, more evidence that quantum biology plays a role in the human brain. GABA is found mostly as a zwitterion, that is, with the carboxy group deprotonated and the amino group protonated. Its conformation depends on its environment in the brain and spinal cord. The stabilization is about 50 kcal/mol, according to quantum chemistry calculations.

Wrapping it all up…….

What affects neurotransmitter formation in humans?

1. Stress/Cortisol……this depletes transmitters and increases their turnover especially over training and obesity
2. Aging……60% of all adults past 40 years old have some degree of neurotransmitter deficiency. Aging neurons also make less NT than young ones.
3. Improper dieting…….limiting food groups dramatically affects brain chemistry within three weeks.
4. The leaky gut…….probably the largest single cause of NT loss and deficiency due to altered absorption and inflammation at the brain level. This is the source of the GAPS diet. Glutamate,glycine, arginine and ornathine are incredibly important AA for gut integrity. A paleo diet provides us with these in abundance.
5. Abnormal sleep……generates IL-6 and alters the conversion of serotonin to melatonin and leads to serious depletion of DHEA in most people with sleep disturbances.
6. Medications….diet pills, stimulants, recreational drugs deplete NT’s, ephedra and ma huang deplete NT’s
7. Neurotoxins……heavy metals, pesticides, BPA, cleaning solvents, ecstasy, nicotine, alcohol, MSG.
8. Hormones……..if there is any hormone imbalance there will be major NT production issues in our brains. It is mandatory that bioidentical hormone replacement be considered in tough cases with stalls and serious mood disorders. Growth Hormone deficiency, which occurs in women at 35 and men around 50, leads to a “leaky gut” by depleting the body of glutamate, glycine , arginine and ornathine from dietary sources. Estrogen can cause a dramatic shift in the production of serotonin or its transport to the brain. DHEA and pregnenolone deficits decrease melatonin production and are very common in those with poor sleep. Progesterone is very commonly seen in poor sleep in women with menopause and men with andropause and exacerbates the ability to learn and neural plasticity as we age. Progesterone directly affects brain derived nerve growth factor needed to make new neurons. In many neurosurgical patients we find dramatic changes in progesterone levels that directly effect recovery from stroke, trauma or tumor repair.
9. Epigenomics/genomics…..those with epigenetic histories that favor mental illness are notoriously poor in production in some NT production. Drug addiction, autoimmune conditions and alcoholism also can predict future NT disorders. This is likely the major way mental illness affects subsequent generations in my opinion.
10. The Brain is the key to it all. Remember we are all losing neurons every single second of the day. In a two hour period, most of us will lose about 6500 neurons! But some of us (AD OR PD) may lose a great deal more. Some will lose 60,000 neurons. Others may lose 600,000 neurons. It’s different for every one of us based upon the status of our epigenomic switches in the current settings. There are many factors that contribute to this increased level of destruction as we have seen above.

One of the ways we can counteract the normal loss of neurons is through neuro-plasticity. If we provide the brain with the proper substrates for optimal health and maintenance we can allow our genes to retool the brain while we sleep with the process of autophagy. This is the process by which a healthy brain can change to better cope with the environment it finds itself in now. This is precisely what epigenetics is. If an area of the brain is damaged and dysfunctional, another area can take over some of the function if we give it the tools to do so. As we fire a specific pathway repeatedly over time, it becomes more and more efficient. This is how we learn. During sleep these pathways become hardwired. If you don’t sleep you will learning suffers tremendously. If you don’t sleep your metabolism suffers tremendously. If you don’t sleep well your much more likely to have mental illness too. It is all based upon the building blocks of how the brain is made. Lipids and NT’s are critical to optimal functioning. So, while we are constantly losing neurons, our pathways can become more efficient and responsive to our current environment. We can actually have a higher level of function as we get older. I can tell you as a neurosurgeon people who have adapted their diet to this evolutionary approach I have laid out here have seen their cognitive scores rise. There are specific hormone tests we can use to see the affect of how improving your diet directly affects the brains function and sleep. People who sleep poorly tend to have very low levels of DHEA-S in their blood or saliva. This level correlates well with high levels of IL-6 in the CSF of the brain and blood. Once we correct the diet this all reverses. The easy way to assess it is to ask the patient if their sleep has improved but I want to see how much better with their DHEA levels. That way I can push them harder or slow them down. It just depends on your outlook. I want a straight A for my patients. I don’t like settling for a C or a D in anything I do.

CITES:
1. http://www.rockwellnutrition.com/assets/images/docs/SupportNeurotransmitterProduction.pdf
2. Kandel & Schwatrz textbook.

Comments

  1. Dr. K, great information as always but I have a question regarding hormonal imbalances. I'm in week 8 of the leptin reset and have not lost any weight but I show signs of high cortisol and maybe a bit of estrogen dominance. The thing is I can't afford to test for these right now due to finances but will continued adherence to the leptin reset protocol beyond the three weeks help to reverse these issues or is some type of medical intervention necessary to alleviate them?

  2. My sleep is better than before the reset but still not optimal, I don't have a lot of trouble falling asleep but I still wake up a couple of times a night and I do have problems with a lack of energy during the day. However my cravings are gone and the softening of the skin you mentioned is very noticeable as well. My last TOM I had no cramps to speak of and none of the hormonal acne either. So it is working just no weight loss. I did have to do a 5 day round of penicillin for an infection but that ended a few days ago. Are there supplements that could help me? Thanks for taking the time to answer my questions.

  3. Hey Jack, remember Lori? She has super high cholesterol and refuses to take statins,cause in part what you say they are crap! She asked me to ask you what else can she do or avoid to get this under control. Also last week she was told that she has Lupus! She thinks that she only has 5yrs to live, please tell me this isn't true? He mom died from that at the same age that Lori is now!! It can be managed from what I have researched right? I understand that there is no "cure" but would she benefit from what we are doing with the lifestyle changes? By the way I have lost 48lbs!! THANK U Kids look great to Sid lost 38 and Rob 42, awesome. Eli's blood pressure is coming down too!!!

    • Lupus is an autoimmune disease. If she does not have Robb's book she needs to get it and make it her bible. She will need to eat the autoimmune version of a paleo diet which is tougher. No grains, omega 6's, no dairy at all. Its not a fatal disease but it can kill you. Why? Read this blog I wrote and share it with her. If she changes her life she can live long. Choice is hers. http://jackkruse.com/where-autoimmunity-cancer-an

  4. Dr.Kruse

    I'm currently in week two of the Leptin Reset. I'm still having to take meds for insomnia answer bipolar as well as Levothyroid and Omeprazol for acid reflux plus meds for chronic pain from my SI Joint. I haven't been able to work since December.

    From reading this I'm guessing that all my problems stem from my being a recovering addict even though I have almost 20 years of recovery.

    My question is how long is average for the LR to start working? I've finally started sleeping through the night but can't get to sleep without the meds yet.

    BTW I'm 5'10.5" tall and am currently 286 lbs. When I started the LR I was 298.5 but part of that was surgery weight from an abdominal hysterectomy.

    My second question is that the LR had restricted my appetite so much I'm concerned I'm not eating enough. I have stalled in the past from that.

    • Couple of things…..it may take you a bit longer. But one thing that I would strongly suggest you talk to your doc about it changing you thyroid medications from a synthetic to a bio-identical. Organic chemistry tells us if it is not precisely stereo chemically the same it is not the same. If you cant tell I am not a fan of synthetic hormones well now you know. I would also consider getting you off the gut reflux drug because it will hinder your absorption of certain minerals you clearly need for your thyroid for optimal functioning. Look into betaine HCL pills instead OTC at a vitamin shop. It works well for reflux and does not have the side effects of the med your own. I also would ask you to consider starting a probiotic and consider fish oil supplements. It is a big deal especially with someone with your history. Your dose may also may need to be titrated up until you feel better. The goal is to get you off all meds and by you continuing to eat a VLC paleo diet you will. IF you don't have Robb Wolf's book get it. Read it and live. You have questions ask me. You can do this all and change your life. How is your sleep? If not good you need to consider adding some other things as well. If your doc orders a lipid panel on you too at some point ask them to do a VAP type instead. Read my blog on the VAP test and you'll see why. It tells me a lot about your gut. And you rgut tells me a lot about your brain and what is at the root of the problem. Its like medical detective work! LOL

  5. Gotta love predictive txt…. that would be and bipolar not answer!

  6. Ty Dr.Kruse!

    I've already started omega 3 fish oil and coconut oil( extra virgin).

    I will go to the health food store and get the supplements for the reflux and probiotics.

    My doctor is surprisingly supportive of this! I'll send her an email about the thyroid med! Clearly it isn't working well since I have to take the highest dose that it comes in.

    Yes I've suffered horrible insomnia since 2005. Funny thing I discovered Atkins iin 2000 and while eating only unprocessed foods and vlc I went without all meds but thyroid for 4 years but then met my husband and started eating sugar answer crap and gained nearly allow my weight back. I never did getting below 225 lbs though but felt healthier than I every have!

    Currently my husband calls me a walking pharmacy! I'm hoping to change that ; -)

    • If sleep is bad you need to talk to PCP about the following……NAC, Sillymarin (feverfew), curcumin, alpha lipoic acid, a fairly high dose of DHEA for sure, and if your peri or post menopausal adding two biggies…..prometrium and a touch of parlodel. These things will jump start your HPA axis. But you must run them past the doc. I purposefully did not put dosing in there and wont.

      Regaining your sleep is critical to your success in weight loss. DHEA, Prometrium, melatonin oxytocin all are huge to restoring your sleep………and I mean huge. I would also encourage you to buy block out curtains and start really monitiring your light intake. If you dont know about the biology of sleep……read Lights Out. Its got a lot of woo woo in it……but its got a lot more gold in it too. Every one should read it.

  7. About 80% of your body's Serotonin in the gut (vagus nerve?) I have heard that diet soda can interfere with the uptake of Serotonin. Is this true and clinically relevant? Very often people trying to get off sugar go to diet drinks and I try to discourage that in my patients.

  8. @Que….only 60% of serotonin is in the gut. And yes diet soda is huge blocker of serotonin because of maltodextrin in diet soda. It completes with tryptophan. Maltodextrin gets changed to glucose eventually so even though the govt says it has no calories…..you need to avoid it in my view. Just more processed crap to avoid. The vagus nerve is an amazing structure and will get it's own blog post soon. The vagus is parasympathetic and uses acetylcholine as it's transmitter but it controls and modulates the enteric neuronal system and all it's hormones.

  9. Ok ty very much! I just sent my doctor a link to this page so she can read it all. So sorry for the typos I'm doing all this from my phone!

    I already have the blackout blinds and go to bed by 10:00 and on good nights I'm asleep by 10:30-11:00. In the hospital I didn't sleep the night of surgery but was doing so good my obgyn let me out the next day.

  10. I had the pleasure of seeing you all fired up at the AHS, I was in the small group listening to your reaction to Ms. De Coster after the closing remarks.

    Jack, you are amazing, your passion for helping others is strikingly genuine. I was moved by you, inspired by your emotions, and am amazed at the in-depth information on your blog.

    I have a question though. I was diagnosed with hypothyroid, B12 deficiency, and low pregnenolone, DHEA, and testosterone. I tested positive for thyroid antibodies as well.

    I have Robb's book and tried the autoimmune Paleo diet, but a ketogenic diet seems to make me feel better and regulates my weight better. So, ketogenic it is for me, mostly meats, eggs, & limited veggies.

    My question is about supplementing. Doc has me on armour thyroid and B12 injections. He wants me on Pregnenolone and DHEA because my levels are very low. Is that a good idea to supp. with Pregnenolone & DHEA or is it time for a new doc.?

    I am 43 yrs. old, achieve optimal vitamin D levels through sun & supplementation, exercise or play most days, and I sleep well. I competed in natural bodybuilding for about 5 years, currently work as a paramedic and personal trainer, and I'm embarking on RN school this September.

    Your thoughts are greatly appreciated! Thank you.

  11. I am a huge, huge fan of bioidentical hormones. I had an ovary rupture at 14 (wish I knew then what I know now about hormones) and the 2nd one went bad and was babied along until I was 23 when I had it out too (so entered surgical menopause at that time.) I was on the standard Premarin then estrace for 35 years. The weight just kept climbing in spite of low carb diets. I went from 2 migraines a week that lasted 3 days each to daily migraines. 4 years ago I discovered Dr. Dzugan who had worked at LIfe Extension and his bioidentical migraine protocol. No more migraines now. I have sooo much energy. I was also starting to get cataracts and mentioned it to the doctors. Dr Rozakis said oh that will go away on the hormones. By golly, he was right!

    I really believe the bioidentical hormones are the key to optimal health. I feel fabulous, even though I'm 59. And now that I've discovered you and the leptin reset, I think the last remaining issues I have since losing so much weight on hcg (75 pounds) will soon be resolved. I have reread the Hormones 101 post a dozen times and have told a lot of people about it. Thank you for all the time you've giving to all of us, Doc. You have a good heart and really care. It shows! :)

  12. @cma77. You may want to consider talking to your doc about starting DHEA and Pregnenolone, nac, and silymarin. Without testing you can't go for bigger guns to go after the sleep issue. Sleep is vital to weight loss. I'm also a big fan of resveratrol but it cost some bucks.

  13. Thanks again Dr. Kruse

    In this discussion of the GAPS diet

    http://www.gaps.me/preview/?page_id=28

    It says to eat fish (bought fresh or frozen, not smoked or canned)—may I ask what the problem is with smoked or canned fish? Are canned herrings and anchovies out even if the only other ingredient is olive oil?

    A separate question, how to add the hormone substrate pregnenolone back to my diet?

  14. majkinetor says:

    Hello there. Great article, thx for that. I hope you have time for few questions.

    – You say MSG is toxin, but it rises glutamine potently. For healthy people, why should it be of concern ?

    – You didn't mention that chronically high cortisol levels deplete body of ascorbate acid which is used in synthesis of dopamine and for good vascular function. Apart from that, brain is one of the organs that contains the highest levels of ascorbate. Do you have any thoughts on it ?

    Thx.

  15. Grammasmitty says:

    Dr. K, would you add a feature to your website? Would you please put up a page with all the Blog titles listed in order of posting, making them links to the blog itself? This would make it so much easier to go back and find a particular blog to re-read it. You've got the categories, but a title list would be so appreciated, too.

  16. Resurgent says:

    "..The Acetyl CoA comes from metabolic breakdown products of glucose and fructose.."

    Does this imply Ach deficient people should be having more glucose/fructose in their diets along with eggs etc. for choline?

    • Fat provides (via beta oxidation) a lot more Ach than equal amount of glucose or fructose. Fat should always be top of the list because of its nutrient density

  17. Adriana G says:

    Another couple of suggestions for the webmaster.

    1. Make the comments accessible from the the main blog page

    2. Be able to get notified when new comments are added to a thread, right now you have manually check each and every one on a regular basis. You provide a lot of in- depth explanations and clarification in the Comments.

  18. btw my question above of course refers to fish canned with olive oil, not vegetable oil

  19. Thanks Jack, she is afraid she will die soon. Her mom had this and died within 5yrs of learning she had it!

    I will send her my book. Thanks for the info. Will his book also help get her super high cholesterol undercontrol?

    Thanks :)

  20. ADD is a disorder with no known cause but with several very interesting associations. I personally believe based upon my readings that it is an epigenetic condition caused by hypermethylation of genes involved in dopamine transport proteins. That does not end the story. I think the disease is made worse as one ages because patients also have comorbid sleep disorder. To date no one scientist can accurately state what the purpose of sleep is but there are many theories. My belief is that sleeps main purpose is to allow the brain to thin slice data coded that is "hard.". What? If you learn something tied to emotion or that is stressed or learned in stress this hard data is thin sliced into our association cortex for use in the forebrain bundle to help us build a relational database of our envirnoment that will help us understand our surroundings and make better predictions on how to live within it and how to associate things to other soft and hard concepts. Sleep in humans is set to a circadian rhythm of close to eight hrs. Humans need that amount of sleep due to the shear size and number of nerve cells. It takes a lot of time for the brain to perform housekeeping on these cells for plasticity of learning and to strengthen the distal synapses where 99% of energy utilization occurs during awakeness. The protein transcription occurs and has to travel substantial distances to replenish and strengthen the machinery. In ADD you have already defective machinery and disordered sleep. A double whammy. This is why ADD seems to get worse as we age and usually ends in depression but begins with problems of inattention to our surroundings and impulsivity. This makes it tough to build a relational database of our environment. Since the environment is not properly coded for in memory extra circuitry is need to bridge gaps. Serotonin becomes a big problem because it get overwhelmed since the dopamine tracts can't code memory in the medial temporal lobe. This leads to an imbalance of serotonin and eventual depression and worsens the issue further. Depression becomes the main issue later not impulsivity because their is a temporal issue for building your three dimensional reality of the world. The more disordered it becomes the more dysfunction the animal is and the more depression results because reward circuits are not naturally selected for when our surroundings can't be coded properly. Failure circuits become hyperactive. This is seen in PET scans of older ADD patients. The rest here is from wiki. It includes the gene variants that we see in kids with this. The ADD subtypes that respond to adderal make up a very small percentage (9%) of cases due to a specific epigentic change in LPHN3. That it why i am not a fan of treating all kids with stimulants. Stimulants also have big unintended side effect of uncoupling metobolism from leptin signalling so these kids always grow up with weight and thyroid issues compounding their clinical picture. The worst reverse T3 levels i have seen are in ADD adults. That makes dealing with their diets real tough. The data on transporters is copied from wiki…..enjoy! Twin studies indicate that the disorder is highly heritable and that genetics are a factor in about 75 percent of all cases.[25] Hyperactivity also seems to be primarily a genetic condition; however, other causes do have an effect.[42] Researchers believe that a large majority of ADHD cases arise from a combination of various genes, many of which affect dopamine transporters. Candidate genes include α2A adrenergic receptor, dopamine transporter, dopamine receptors D2/D3,[43] dopamine beta-hydroxylase monoamine oxidase A, catecholamine-methyl transferase, serotonin transporter promoter (SLC6A4), 5HT2A receptor, 5HT1B receptor,[44] the 10-repeat allele of the DAT1 gene,[45] the 7-repeat allele of the DRD4 gene,[45] and the dopamine beta hydroxylase gene (DBH TaqI).[46] A common variant of a gene called LPHN3 is estimated to be responsible for about 9% of the incidence of ADHD, and ADHD cases where this gene is present are particularly responsive to stimulant medication.[47]

  21. if it is an epigenetic condition, is there an epigenetic solution?

    • yes there is in my view and that is going to happen in the next 25 yrs or so. Right now the best we have is understanding how the biochemistry of energy metabolism is translated by the brain into the hormone response. This is the Rosetta Stone of how epigenetic switches are set. What we dont fully know yet is how to reset them. It appears that time and stimulus response are critical in that maneuver.

  22. Is choline supplementation recommended for the various Ach deficiency issues? I know it's also supposed to be very good for countering NAFLD.

  23. Today, I just stared doing the Leptin reset prescription. I'm glad I found your insomnia articles because in the past I got horrendous insomnia when I tried VLC diets. But this time, maybe things will be different.

    I stopped eating wheat 3 weeks ago (along with MSG and maltodextrin containing food) and I've been at 100 grams per day or less of carbohydrate for over a year now. Based on what I've read here and around the web (and my history of restless leg) I've "splurged" and ordered a magnesium supplement. Also, given that I'm perimenopausal and in a stressful job, I also will try 5-HTP and DHEA to see if they help me cope with this transition back to LS. Here's hoping that staying with a paleo/primal diet for the rest of my life and getting my metabolism sorted out means that my body will make the things it needs in the correct quantities in the future.

    Two thumbs way up for this blog being so packed with information. I feel like I'm getting to read a nutritional biochemistry textbook with a side of endocrinology and basic neuropathology tossed in too.

  24. Jacqueline Joy says:

    Please consider writing an article specifically about what you recommend to your Patients with Parkinson's.

    I am the sole caregiver for my husband, and so many of the dietary recommendations suggest being careful with protein and meal times, because of the protein fighting with carbidopa/levidopa meds.

  25. Jack, could you please elaborate a bit more about carbs and serotonin? Is it possible to have a functioning serotonin synthesis on a keto diet?

  26. Gabriellank says:

    Hi Jack: I posted somewhere else on this site but cannot find it! I read some of your artciles, but right now am having trouble focusing. I see major gut issues since the onset of menopause. I have a very well know person working with me on the hormone part, but seem to keeping having cortisol issues and i think thyroid uptake stuff (have hashimotoes) all my reactions are paradoxical and i think caused by the RT3 and severe gut issues, neuropathy showed up as well and it seems like the thyroid, et al cannot seem to get balanced and get the gut balanced and the adrenals, DHEA, Pregnenalone. etc. My doc needs your help to or need to see you. Can I make an appt. We are very frustrated, but HE is very committed to finding the answer as to why I keep gaining weight (50 lbs) since starting biodentical hormones–was 125 lb. now 170 lbs. and the hormone doses are lower than all the quacks out there. Can we work with you? thank you.

    • @Gabriellank My bet is you have a leaky gut and you have a dopamine issue. Read the blog on from 11/27/2011 It mentions the dopamine test. Tell your doctor to consider into bromocriptine low dose to help. This topic is covered in detail in my upcoming book.

  27. Gabriellank says:

    Hi Jack, I agree with you on the leaky gut and dopamine issues. However, my doctor is not versed in this. I need someone to help us on how to approach this from the whole body perspective. Right now he is only focusing on hormones and has suggested multi-vitamin and a very expensive Meta-metrix test because he does not have the kind of knowledge you are displaying here. Is it possible for me to come to your office for assistance? Thank you sincerely. Gabriella

  28. Hi Dr. Jack, I know it must be difficult to answer every ones queries but I am having an extremely hard time adjusting to the leptin reset. I have been paleo/primal for almost two years. I lost a lot of weight at first but over time no matter what I did the scales started to creep back up. During times of heavy stress I have been battling bulemia from time to time and I know that this contributed to a lot of my current weight issues. My sleep is all over the place and since starting the reset my instances of bulemia have increased. With the article and the statement of serotonin and a lack of dopamine in cases such as mine, should i include anything else besides 5-Htp as well as the other recommended supplements as many as I can afford of course. Which are going to be the most most important. Any help no matter how small would mean the world. Btw I was diagnosed with Lupus at 13 and am now 30 and I know for sure that grains have a high impact on my symptoms and my recovery. Just getting over this hump is frustrating and I feel I need a little extra. Thank you. Amanda

    • @Amanda there is no way to know definitively what is up with you based upon what you have given me here……..but I have some thoughts……without testing but I dont think supplements are your major issue. I have a sneaking suspicion that your real problem is a problem of activation of your endogenous endocabinoid and endorphin systems and their disconnect with leptin and the incretin hormone systems in their proper circadian cycle. Most eating disorders are very much like narcolepsy. They are results of improper firing and timing of large neural loops occuring in their proper sequence. If you really want to learn more about this read some of Dr. Luis LeCea work on Narcolepsy from stanford University.

      My suggestion for you is to start krill oil 500 mgs three times a day, stop the reset and immediately start and begin to eat like the Leptin Rx post script. I would also like to see if your doctor would consider starting you on low dose naltrexone therapy to see if this makes a difference. Sadly, I bet none will do so because this is an area of brain physiology that few conventional MDs have any concept of. The ID physicans who took care of HIV patients back in the 1980's are the ones who gave us the links between the endorphins system and our immune systems activation. I think this might be at the seat of your current dilemma. My bet is you current alpha MSH level is cratered and your HS CRP are up and your leptin resistant due to some cytokine abnormaility. That is pure speculation but I think it might be at the seat of your issues. Good Luck try to fix it with the dietary change if you can. I also will tell you something else that wont make sense to you know but if you put ten pounds of ice on your abdomen for 45-hour at a time for next few days you may see dramatic changes too……….and no I wont go into why. I know it wont hurt you so that is why I am telling you about it.

  29. Im sure the docs in my small town will have no clue what you are talking about. Thank you for your advice and I will follow it to the t. The ice is strange but i will try it. You never know. Thank you. Amanda

  30. I finally get why the anti aging is important. I found the European study on bio identicals. I am getting the glasses, but was wondering if the time of day for the cold matters? We are just trying to get used to it, right?

  31. Daniel Han says:

    I'm confused, here you state that maintaining normal serotonin levels requires carbohydrate intake yet you are completely against safe starch and only eat fruit during summer. How are we supposed to get an adequate amount of serotonin following a ketogenic diet? Or is it the protein that stimulates insulin…

  32. Julian Court says:

    Jack..I have been on and off anti-depression/anxiety drugs now for 17 years…manage to come off them often (peroxitine hydrochloride) only to have a relapse some weeks/months later. How can i cure this crippling disease through nutrition?..is it ok to supplement 5htp while on the peroxitine?..

    • @Julian read the brain gut series as it develops. 5HTP could seriously hurt a bad brain……especially if it is a vegan or vegetarian brain for any extended length of time before using 5HTP or GABA

  33. Julian Court says:

    ..(CONT)..would a supplement like GABA help?

  34. Hi Dr K. My husband is a clinical psychologist within addiction and has been hired to consult with a city-wide detox program (mostly alcohol detox). Patients stay for 7-14 days, 24 hours per day. He has begun to discuss things like circadian/light cycles and dietary changes and we’ve been re-reading many blogs. If you were in his shoes and had only this short-time frame to try and help alcohol addicts (and change the system you’re working with), what would you be focussed on? (The food comes from the main hospital cafeteria, so can request the absence of things (e.g. sugar and grains) but not necessarily the inclusion of anything.) After detox, they go a variety of ways (home, to long term inpatient treatment, to outpatient treatment, etc) so no consistency. I realise it’s mission-impossible with the set up, but he’s out to change the system and would really like your input on the first steps you’d take. Thanks!

    • @Lauren……..my next blog (Brain Gut 5) gives you that answer in detail. It maybe the most actionable blog I will ever write in this space. It’s implications might be broad to mankind to say the least.

  35. Zorica Vuletic says:

    @ Lauren, I don’t know if there are laws about the outside food, or if it’s only based on finances….but sea veggies of all sorts cost 99 cents a bag in most Asian stores. One bag provides dozens of servings. You reconstitute it in water, and trust me, the servings are large.

    Hope that helps.

    Good luck with it all!

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