redsun
Member
- Joined
- Dec 17, 2018
- Messages
- 3,013
I made this thread to share some of the things I have learned along the way in a generally less organized format. I figured that making a thread for every little thing is inappropriate and too time consuming. Most of this is info is neurotransmitter related but not all. Some things I have already posted about but some I have not needed to utilize specifically. I will probably continue to add to the list over time:
High levels of endogenous opioids can lead to reduced social motivation, libido, testosterone, as well as cognitive dysfunction and anhedonia. This is primarily due to reduce dopaminergic and glutamatergic neurotransmission but is also due to direct effects of the opioid neuropeptides themselves on gonads. Too low causes the opposite problems as well as anxiety and increased risk taking. There isn't too much info you can find on how to affect basal activity. But in essence, chronic stress causes high levels as these opioid peptides are secreted alongside other stress hormones such as cortisol and the catecholamines.
Any substance or metabolic state that increases the body's perceived stress due to enhanced metabolic demands, or direct stimulation of the sympathetic nervous system will contribute to higher basal activity of stress hormones, and endogenous opioids which will then lead to effects mentioned above. Some examples include hyperthyroidism, anemia, nonanemic iron deficiency, long-term reduced calorie diets, erratic eating behavior due to eating disorders, infrequent eating ( think intermittent fasting), excessive caffeine or other stimulants or drugs, excessive exercise or high levels of daily life stress with poor stress management.
This also means too much instant gratification and pleasure seeking activities can make you less motivated to accomplish desirable long-term goals. This does not mean you should not enjoy things. You should, and if you don't its the same as being dead in my opinion. But what this does mean is you should moderate in how much of your time is occupied in regards to this. Also it makes more sense to do be more occupied with work and other productive endeavors during the day and pleasurable and leisure activities are down in the afternoon. This helps you wind down and relax as well. This is why opioid addiction can destroy your life. You get the feel-good endorphins without the effort needed to obtain them doing normal activities. An addict has no need to seek pleasure and fulfillment from anywhere else but a pill. Opiates effectively skip the effort part and give you the reward immediately.
Intolerance to stimulants can be due to sympathetic dominance and/or reduced parasympathetic tone. This can also occur in those with hyperthyroidism. Those who are sympathetic dominant tend to find it hard to relax and are prone to elevated BP, heart rate, nervousness and anxiety, mental overstimulation. Even small amounts of stimulants will exacerbate all of these tendencies. You may crave and may even be dependent on downers such as alcohol, benzos, opioids, calming herbs to help you wind down and also help you sleep. Priority should be higher choline intake so there is sufficient acetylcholine signalling to properly regulate and control the sympathetic nervous system. Calcium, magnesium, zinc, can also be helpful for these individuals if intake is low. Anemia will also lead to increased sympathetic activity, so treating it would also be helpful to reduce anxiety, nervousness, and tension.
This is not that common but some also have severe intolerance to essential nutrients such as vitamin D, iron, copper since they can have stimulating effects. If you are one of those people who gets insomnia, even severe insomnia from vitamin D for example, this points to sympathetic dominance that vitamin D is amplifying even more.
Intolerance to downers such as the small amounts of opioid peptides in dairy, wheat, and downer drugs/herbs can indicate parasympathetic dominance and/or reduced sympathetic tone. A major reason for reduced sympathetic tone could be hypothyroidism, as well as lack of protein and overall a diet poor in nutrients in the diet leading to reduced synthesis of excitatory neurotransmitters. Low copper is also a reason for this through decreased catecholamine synthesis causing low adrenergic tone. Though this is uncommon unless you supplement large doses of zinc for long periods of time. Hypothyroidism is the more likely cause of low adrenergic tone.
Muscarinic receptors can reduce release of noradrenaline in the locus coeruleus and thus reduce locus coeruleus firing, which can decrease activation of the amygdala, reducing anxiety-like behaviors.
Dietary Vitamin A as retinol is an effective way to improve skin quality overall even if you have no observable acne. Just one ounce of liverwurst a day, every other day, or just a few times a week is a great way to do this without going overboard. Dairy and eggs as well also contribute retinol intake. The major issue of vitamin A is not toxicity (unless you go insane with the dose for many months) but rather increased bone resorption over time which in the long term will reduce BMD. Supporting nutrients to appropriately utilize dietary retinol for improving skin health are zinc, B3/NAD, and iron/B-vitamins (to make NAD endogenously from tryptophan). Just to clarify, vitamin D and calcium does not treat vitamin A toxicity, it helps improve reduced BMD caused by vitamin A, whether you consume normal amounts of retinol (not toxic levels) or are already toxic with it. If you have toxicity you need to allow stores to deplete to properly restore BMD with the appropriate nutrients.
Hypothyroidism or compromised energy metabolism can sometimes contribute to insomnia because all of the major transporters that remove excitatory neurotransmitters from the synapse such as glutamate, dopamine, norepinephrine, serotonin, depend on the sodium-potassium pump, also known as Na/K-ATPase which utilizes ATP to maintain ion concentration gradient which makes transport possible. It may also be due to very negative outlook on life and increased risk of mental disorders in hypothyroidism that make it difficult for you to relax and stop stressful thought patterns which prevent you from falling asleep.
Excessively high acetylcholine activity is very uncommon, however anything that can raise cyclic AMP levels directly or indirectly may increase the expression of acetylcholinesterase. Forskolin (well-known cAMP inducer), Caffeine, stimulants in general, zinc (positive allosteric modulator of beta-2 receptor), Iodine (increases sensitivity to adrenaline, a major inducer of cAMP, by increasing thyroid hormone), copper (needed for catecholamines). Anything that helps increase low thyroid hormones (treating deficiencies or taking actual thyroid hormone like NDT) also would work.
The negative symptoms and signs associated with hyperthyroidism are incredibly similar to symptoms of epinephrine overdose. This is because thyroid hormone upregulates expression of beta-adrenergic receptors, making you more sensitive to your own epinephrine.
Like endogenous opioids, there is not that much information on modulating glutamate. If you want to increase glutamate activity (to treat anhedonia, low libido), some things that can help are caffeine, high protein diet, higher salt intake, choline (Ach can enhance glutamate release), zinc/copper (both are GABA-A antagonists but both metals can also directly block NMDA receptors, so avoid excess intakes), arachidonic acid (reduce glutamate transporter expression, reducing uptake of glutamate), manganese (avoid high dose supplementing, neurotoxic), reducing endogenous opioids. Too much zinc can be anxiogenic due to GABA-A antagonism. Copper can be anxiogenic due to enhanced catecholamine synthesis.
To reduce excessive glutamate: retinol, zinc, copper, magnesium, improving ATP production by treating hypothyroidism, fixing nutritional deficiencies that are compromising ATP synthesis and getting enough carbs.
Potential reasons for elevated heart rate: thiamine deficiency, anemia, hyperthyroidism, low parasympathetic tone,
excessive stimulant usage
Potential reasons for low heart rate: hypothyroidism, solanine poisoning from high consumption of potatoes (especially with skin), parasympathetic dominance, excessive cardio
Skeletal muscle tone is the passive contraction of your muscles while you are awake which is maintained primarily by glutamate sending signals to motor neurons. When the signal from the brain reaches the axon terminal (end of the motor neuron), it triggers acetylcholine release to bind to receptors on the plasma membrane of the muscle cell. Receptor activation triggers a signal to release calcium inside the muscle cell to trigger muscle contractions. Catecholamines amplifies the signalling of glutamate to motor neurons. This is why adrenergic tone is so vital for strength (and why caffeine, which increases catecholamines, is used for sports performance).
Knowing this, if you generally seem to lack muscle tone and are generally weak despite lifting heavy weights, there is likely some issue in this pathway. Hypothyroidism causing low adrenergic tone will contribute as the glutamate signal to contract will be too weak due to reduced sensitivity to catecholamines, so there is not enough signal. Treating hypothyroidism will improve tone and overall muscle strength.
If signalling is not the issue, it could be lack of actual acetylcholine to properly maintain muscle tone due to low dietary choline intake. Lack of salt will also cause weakness since sodium is needed for glutamate and acetylcholine to work through their receptors. Sodium and chloride are also needed to transport free choline, after acetylcholine is broken down in the synapse, back into the neuron to resynthesize acetylcholine.
If you want to help maximize contractile force of your skeletal muscles for the sake of increasing your strength on lifts or for more strength in general and muscle tone (make your muscles appear denser), you should aim for a minimum of 800mg choline a day which will help overcome issues with PEMT enzyme which are very common in europeans due to ancestral diets being much higher in dietary choline than they are today, which meant there was no advantage at the time for those with better functioning PEMT enzymes, so it never got selected out.
Strength is more complex than this but these are some good practical steps to take. Strength of course is also related to energy metabolism and resistance training primarily utilizes the creatine phosphate system and glycolysis to produce the ATP needed because these systems are made for producing a lot of energy in a short amount of time. Hence, creatine supplementation being very common nowadays.
Even ignoring PEMT gene variants, men are even more dependent on dietary choline due to reduced estrogen levels. Estrogen increases activity of PEMT. Dietary calcium should also be around 1000 mg.
Hypercalcemia (due to high PTH) will also cause weakness and reduced muscle tone as it blocks sodium channels which are needed to send signals. But calcium is still needed for muscle contractions. So it is important a distinction is made:
You want normal extracellular (blood levels) calcium as to not block sodium channels from sending signals, but you need intracellular (inside the muscle cell) calcium to contract the muscles. So low dietary calcium (and vitamin D) can contribute to weakness. Excess magnesium intake can also contribute to weakness as it competes with calcium for contractile proteins in the muscle. This also makes magnesium good for tight muscles, and magnesium can also increase low PTH, normalizing serum calcium. Too low serum calcium causes hypertonia (excessive muscle tone).
For those who do not lift weights but get easily tired from standing or walking, low muscle tone could be a reason why. Same advice applies.
Increased serotonin activity in the amygdala can treat cataplexy in those with narcolepsy. One proposed mechanism is that serotonin reduces the effects of emotional triggers on muscle tone regulation that cause cataplexy.
NMDA hypoactivity can impair short term memory and your ability to actively learn and stay on task. Sometimes, it can cause hypersomnia (needing to sleep too much to feel normal). Too much zinc and magnesium, GABA agonists, antihistamine usage (histamine potentiates NMDA activity), and low protein diets can contribute to NMDA hypoactivity.
Copper is associated with longer sleep time.
Histamine can be protective against the negative effects of radiation.
The locus coeruleus is needed to maintain arousal during waking periods, and is involved in the heightened arousal response to physical, emotional, and mental stress. This brain region is more sensitive in women due to estrogen enhancing catecholamine synthesis (can enhance TH and DBH), and reducing COMT (which deactivates catecholamines). This reduced COMT activity means women also on average have 30% higher basal dopamine activity than men.
Poor focus is often attributed to low dopamine and norepinephrine but low acetylcholine activity can also contribute. Acetylcholine is needed to maintain sustained attention and lack of acetylcholine due to low dietary choline can contribute to ADHD symptoms. Acetylcholine also reduces distractibility by increasing signal to noise ratio and reducing processing of irrelevant stimuli in the environment.
Long-term high dose retinol can deplete vitamin D indirectly due to bone loss. This triggers vitamin D conversion to active form to absorb more calcium in the gut. So vitamin D can be used up faster if you consume tons of dietary retinol for many months at a time. So if you want to consume more retinol for skin, be moderate in your intake to avoid toxicity and make sure you get enough vitamin D and calcium. You will lose BMD if your vitamin D and calcium intake is too low regardless, but it will be even worse if these are low and dietary retinol intake is high on top of it.
Transferrin bound to iron (also known as transferrin saturation) has a dose-dependent inhibitory effect on mast cells. Normalizing low iron which will raise low transferrin saturation may help reduce mast cell activation.
Because vitamin D inhibits TPH1, which is the form of TPH that is used to make serotonin in the gut, this means vitamin D supplementation can contribute to slowed gut motility, and even constipation. If you do take it, be moderate with how much you take. And if you do deal with slowed gut motility, you may see benefit keeping your supplementation much lower.
TPH2 however is actually increased by vitamin D, which means it can increase serotonin synthesis in the brain.
Individuals with anxiety have higher baseline heart rates as well as stronger heart rate response caused by stressors.
I have tested multiple times and can say reliably in my experience 2mg or more of copper supplements (used copper bisglycinate) lowers my core temperature. I never have lower than 98.6 and temperature is mostly 98.8-99.3 during the day but copper can bring it down to 98.4. Be wary of this if you consume a lot of copper in the diet and temps are consistently low, its possible a very high copper intake may contribute to lower temperatures in some people. This is just an n=1 so I encourage others to experiment as well. Normal copper intakes are considered to be 1-2mg a day. 2mg+ is considered high compared to normal.
Hypercalcemia due to hyperparathyroidism, high levels of exogenous opioid peptides or endogenous opioids, high noradrenaline, hypothyroidism, low histamine, acetylcholine, and/or serotonin can contribute to slow gut motility. Those with higher histamine, acetylcholine, and/or serotonin generally will have faster gut motility but keep in mind it is more complex than this.
Low dietary salt intake can contribute to anhedonia and slow cognition.
If you know you have low cholesterol levels (confirmed by blood test), this may contribute to depression, anxiety, and other mood disorders. Eggs and meat, especially fatty meat and organ meats are the best sources of cholesterol. Increased intake of fructose may also increase it.
Excessive methyl donors such as TMG can sometimes lead to very vivid dreaming for an unknown reason but may have to do with increased expression of acetylcholine and glutamate receptors, melatonin and its interactions with other neurotransmitters. Large doses of niacinamide comparable to the doses used of the methyl donor seems to fix this.
Even though heme-iron supplements cause less gut-related side effects, because the actual percentage absorbed is so low due to saturation of the absorption mechanism for heme-iron, if you want to fix nonanemic iron deficiency or ID anemia in a timely manner, higher doses of non-heme iron supplements such as iron bisglycinate are preferable.
Zinc has been shown to reduce the optimal dose for amphetamine by up to 37% at 30mg a day. This dose long term could pose an issue for copper status however. Zinc is likely important in reducing ADHD symptoms, so fixing a deficiency would be helpful.
Testosterone leads to hypomethylation of the vasopressin promoter (which means it increases vasopressin), which is likely how it reduces fear and anxiety like behaviors in male animals.
PGD2 is the most potent somnogen in man. Some things may reduce PGD2 synthesis if taken, especially late at night can contribute to insomnia. Selenium seems to be one of them.
Methyl donors, copper (with riboflavin for DAO), vitamin C, are known to be able to reduce histamine levels through enhancing deactivation by methylation and diamine oxidase. However this may not work all the time. Sometimes issues with deactivation are not the primary cause of histamine issues. It may help but not entirely.
The other issue could be overactive mast cells due to a lack of inhibitory signalling (mast cells stabilizers). Low adrenergic tone can increase mast cell activation, as well as too low cortisol. So for example copper and vitamin C not only are needed to deactivate histamine, but also are used to synthesize catecholamines which stabilize mast cells. Too low cortisol will also contribute to overactive mast cells. This is why epinephrine is used in medical situations to stop a severe allergic reaction as well corticosteroids used as long-term treatment for allergies.
This brings in to question the issue of caffeine (which enhances catecholamines) for allergies. Pure caffeine does generally help allergies because of this. Coffee can have worsening effects due to potential allergens in the coffee, so higher quality coffee would be preferred in regards to this. But whether is caffeine from beverages or caffeine pills, keep in mind that adaptation occurs which results in your own adrenergic tone being lower.
So if you skip a dose of caffeine that you normally would have, mast cell activity may increase because you have less catecholamine activity to inhibit them due to tolerance. If you are consistent with caffeine dosing (approximately every 5 hours of waking, due to half-life) it's not necessarily a problem. But getting off caffeine entirely will help allergies by restoring adrenergic tone which will no longer rise and dip throughout the day as caffeine levels in the system rise and dip throughout the day. Getting off caffeine may not help as much however if your adrenergic tone is too low due to some other reason.
High levels of endogenous opioids can lead to reduced social motivation, libido, testosterone, as well as cognitive dysfunction and anhedonia. This is primarily due to reduce dopaminergic and glutamatergic neurotransmission but is also due to direct effects of the opioid neuropeptides themselves on gonads. Too low causes the opposite problems as well as anxiety and increased risk taking. There isn't too much info you can find on how to affect basal activity. But in essence, chronic stress causes high levels as these opioid peptides are secreted alongside other stress hormones such as cortisol and the catecholamines.
Any substance or metabolic state that increases the body's perceived stress due to enhanced metabolic demands, or direct stimulation of the sympathetic nervous system will contribute to higher basal activity of stress hormones, and endogenous opioids which will then lead to effects mentioned above. Some examples include hyperthyroidism, anemia, nonanemic iron deficiency, long-term reduced calorie diets, erratic eating behavior due to eating disorders, infrequent eating ( think intermittent fasting), excessive caffeine or other stimulants or drugs, excessive exercise or high levels of daily life stress with poor stress management.
This also means too much instant gratification and pleasure seeking activities can make you less motivated to accomplish desirable long-term goals. This does not mean you should not enjoy things. You should, and if you don't its the same as being dead in my opinion. But what this does mean is you should moderate in how much of your time is occupied in regards to this. Also it makes more sense to do be more occupied with work and other productive endeavors during the day and pleasurable and leisure activities are down in the afternoon. This helps you wind down and relax as well. This is why opioid addiction can destroy your life. You get the feel-good endorphins without the effort needed to obtain them doing normal activities. An addict has no need to seek pleasure and fulfillment from anywhere else but a pill. Opiates effectively skip the effort part and give you the reward immediately.
Intolerance to stimulants can be due to sympathetic dominance and/or reduced parasympathetic tone. This can also occur in those with hyperthyroidism. Those who are sympathetic dominant tend to find it hard to relax and are prone to elevated BP, heart rate, nervousness and anxiety, mental overstimulation. Even small amounts of stimulants will exacerbate all of these tendencies. You may crave and may even be dependent on downers such as alcohol, benzos, opioids, calming herbs to help you wind down and also help you sleep. Priority should be higher choline intake so there is sufficient acetylcholine signalling to properly regulate and control the sympathetic nervous system. Calcium, magnesium, zinc, can also be helpful for these individuals if intake is low. Anemia will also lead to increased sympathetic activity, so treating it would also be helpful to reduce anxiety, nervousness, and tension.
This is not that common but some also have severe intolerance to essential nutrients such as vitamin D, iron, copper since they can have stimulating effects. If you are one of those people who gets insomnia, even severe insomnia from vitamin D for example, this points to sympathetic dominance that vitamin D is amplifying even more.
Intolerance to downers such as the small amounts of opioid peptides in dairy, wheat, and downer drugs/herbs can indicate parasympathetic dominance and/or reduced sympathetic tone. A major reason for reduced sympathetic tone could be hypothyroidism, as well as lack of protein and overall a diet poor in nutrients in the diet leading to reduced synthesis of excitatory neurotransmitters. Low copper is also a reason for this through decreased catecholamine synthesis causing low adrenergic tone. Though this is uncommon unless you supplement large doses of zinc for long periods of time. Hypothyroidism is the more likely cause of low adrenergic tone.
Muscarinic receptors can reduce release of noradrenaline in the locus coeruleus and thus reduce locus coeruleus firing, which can decrease activation of the amygdala, reducing anxiety-like behaviors.
Dietary Vitamin A as retinol is an effective way to improve skin quality overall even if you have no observable acne. Just one ounce of liverwurst a day, every other day, or just a few times a week is a great way to do this without going overboard. Dairy and eggs as well also contribute retinol intake. The major issue of vitamin A is not toxicity (unless you go insane with the dose for many months) but rather increased bone resorption over time which in the long term will reduce BMD. Supporting nutrients to appropriately utilize dietary retinol for improving skin health are zinc, B3/NAD, and iron/B-vitamins (to make NAD endogenously from tryptophan). Just to clarify, vitamin D and calcium does not treat vitamin A toxicity, it helps improve reduced BMD caused by vitamin A, whether you consume normal amounts of retinol (not toxic levels) or are already toxic with it. If you have toxicity you need to allow stores to deplete to properly restore BMD with the appropriate nutrients.
Hypothyroidism or compromised energy metabolism can sometimes contribute to insomnia because all of the major transporters that remove excitatory neurotransmitters from the synapse such as glutamate, dopamine, norepinephrine, serotonin, depend on the sodium-potassium pump, also known as Na/K-ATPase which utilizes ATP to maintain ion concentration gradient which makes transport possible. It may also be due to very negative outlook on life and increased risk of mental disorders in hypothyroidism that make it difficult for you to relax and stop stressful thought patterns which prevent you from falling asleep.
Excessively high acetylcholine activity is very uncommon, however anything that can raise cyclic AMP levels directly or indirectly may increase the expression of acetylcholinesterase. Forskolin (well-known cAMP inducer), Caffeine, stimulants in general, zinc (positive allosteric modulator of beta-2 receptor), Iodine (increases sensitivity to adrenaline, a major inducer of cAMP, by increasing thyroid hormone), copper (needed for catecholamines). Anything that helps increase low thyroid hormones (treating deficiencies or taking actual thyroid hormone like NDT) also would work.
The negative symptoms and signs associated with hyperthyroidism are incredibly similar to symptoms of epinephrine overdose. This is because thyroid hormone upregulates expression of beta-adrenergic receptors, making you more sensitive to your own epinephrine.
Like endogenous opioids, there is not that much information on modulating glutamate. If you want to increase glutamate activity (to treat anhedonia, low libido), some things that can help are caffeine, high protein diet, higher salt intake, choline (Ach can enhance glutamate release), zinc/copper (both are GABA-A antagonists but both metals can also directly block NMDA receptors, so avoid excess intakes), arachidonic acid (reduce glutamate transporter expression, reducing uptake of glutamate), manganese (avoid high dose supplementing, neurotoxic), reducing endogenous opioids. Too much zinc can be anxiogenic due to GABA-A antagonism. Copper can be anxiogenic due to enhanced catecholamine synthesis.
To reduce excessive glutamate: retinol, zinc, copper, magnesium, improving ATP production by treating hypothyroidism, fixing nutritional deficiencies that are compromising ATP synthesis and getting enough carbs.
Potential reasons for elevated heart rate: thiamine deficiency, anemia, hyperthyroidism, low parasympathetic tone,
excessive stimulant usage
Potential reasons for low heart rate: hypothyroidism, solanine poisoning from high consumption of potatoes (especially with skin), parasympathetic dominance, excessive cardio
Skeletal muscle tone is the passive contraction of your muscles while you are awake which is maintained primarily by glutamate sending signals to motor neurons. When the signal from the brain reaches the axon terminal (end of the motor neuron), it triggers acetylcholine release to bind to receptors on the plasma membrane of the muscle cell. Receptor activation triggers a signal to release calcium inside the muscle cell to trigger muscle contractions. Catecholamines amplifies the signalling of glutamate to motor neurons. This is why adrenergic tone is so vital for strength (and why caffeine, which increases catecholamines, is used for sports performance).
Knowing this, if you generally seem to lack muscle tone and are generally weak despite lifting heavy weights, there is likely some issue in this pathway. Hypothyroidism causing low adrenergic tone will contribute as the glutamate signal to contract will be too weak due to reduced sensitivity to catecholamines, so there is not enough signal. Treating hypothyroidism will improve tone and overall muscle strength.
If signalling is not the issue, it could be lack of actual acetylcholine to properly maintain muscle tone due to low dietary choline intake. Lack of salt will also cause weakness since sodium is needed for glutamate and acetylcholine to work through their receptors. Sodium and chloride are also needed to transport free choline, after acetylcholine is broken down in the synapse, back into the neuron to resynthesize acetylcholine.
If you want to help maximize contractile force of your skeletal muscles for the sake of increasing your strength on lifts or for more strength in general and muscle tone (make your muscles appear denser), you should aim for a minimum of 800mg choline a day which will help overcome issues with PEMT enzyme which are very common in europeans due to ancestral diets being much higher in dietary choline than they are today, which meant there was no advantage at the time for those with better functioning PEMT enzymes, so it never got selected out.
Strength is more complex than this but these are some good practical steps to take. Strength of course is also related to energy metabolism and resistance training primarily utilizes the creatine phosphate system and glycolysis to produce the ATP needed because these systems are made for producing a lot of energy in a short amount of time. Hence, creatine supplementation being very common nowadays.
Even ignoring PEMT gene variants, men are even more dependent on dietary choline due to reduced estrogen levels. Estrogen increases activity of PEMT. Dietary calcium should also be around 1000 mg.
Hypercalcemia (due to high PTH) will also cause weakness and reduced muscle tone as it blocks sodium channels which are needed to send signals. But calcium is still needed for muscle contractions. So it is important a distinction is made:
You want normal extracellular (blood levels) calcium as to not block sodium channels from sending signals, but you need intracellular (inside the muscle cell) calcium to contract the muscles. So low dietary calcium (and vitamin D) can contribute to weakness. Excess magnesium intake can also contribute to weakness as it competes with calcium for contractile proteins in the muscle. This also makes magnesium good for tight muscles, and magnesium can also increase low PTH, normalizing serum calcium. Too low serum calcium causes hypertonia (excessive muscle tone).
For those who do not lift weights but get easily tired from standing or walking, low muscle tone could be a reason why. Same advice applies.
Increased serotonin activity in the amygdala can treat cataplexy in those with narcolepsy. One proposed mechanism is that serotonin reduces the effects of emotional triggers on muscle tone regulation that cause cataplexy.
NMDA hypoactivity can impair short term memory and your ability to actively learn and stay on task. Sometimes, it can cause hypersomnia (needing to sleep too much to feel normal). Too much zinc and magnesium, GABA agonists, antihistamine usage (histamine potentiates NMDA activity), and low protein diets can contribute to NMDA hypoactivity.
Copper is associated with longer sleep time.
Histamine can be protective against the negative effects of radiation.
The locus coeruleus is needed to maintain arousal during waking periods, and is involved in the heightened arousal response to physical, emotional, and mental stress. This brain region is more sensitive in women due to estrogen enhancing catecholamine synthesis (can enhance TH and DBH), and reducing COMT (which deactivates catecholamines). This reduced COMT activity means women also on average have 30% higher basal dopamine activity than men.
Poor focus is often attributed to low dopamine and norepinephrine but low acetylcholine activity can also contribute. Acetylcholine is needed to maintain sustained attention and lack of acetylcholine due to low dietary choline can contribute to ADHD symptoms. Acetylcholine also reduces distractibility by increasing signal to noise ratio and reducing processing of irrelevant stimuli in the environment.
Long-term high dose retinol can deplete vitamin D indirectly due to bone loss. This triggers vitamin D conversion to active form to absorb more calcium in the gut. So vitamin D can be used up faster if you consume tons of dietary retinol for many months at a time. So if you want to consume more retinol for skin, be moderate in your intake to avoid toxicity and make sure you get enough vitamin D and calcium. You will lose BMD if your vitamin D and calcium intake is too low regardless, but it will be even worse if these are low and dietary retinol intake is high on top of it.
Transferrin bound to iron (also known as transferrin saturation) has a dose-dependent inhibitory effect on mast cells. Normalizing low iron which will raise low transferrin saturation may help reduce mast cell activation.
Because vitamin D inhibits TPH1, which is the form of TPH that is used to make serotonin in the gut, this means vitamin D supplementation can contribute to slowed gut motility, and even constipation. If you do take it, be moderate with how much you take. And if you do deal with slowed gut motility, you may see benefit keeping your supplementation much lower.
TPH2 however is actually increased by vitamin D, which means it can increase serotonin synthesis in the brain.
Individuals with anxiety have higher baseline heart rates as well as stronger heart rate response caused by stressors.
I have tested multiple times and can say reliably in my experience 2mg or more of copper supplements (used copper bisglycinate) lowers my core temperature. I never have lower than 98.6 and temperature is mostly 98.8-99.3 during the day but copper can bring it down to 98.4. Be wary of this if you consume a lot of copper in the diet and temps are consistently low, its possible a very high copper intake may contribute to lower temperatures in some people. This is just an n=1 so I encourage others to experiment as well. Normal copper intakes are considered to be 1-2mg a day. 2mg+ is considered high compared to normal.
Hypercalcemia due to hyperparathyroidism, high levels of exogenous opioid peptides or endogenous opioids, high noradrenaline, hypothyroidism, low histamine, acetylcholine, and/or serotonin can contribute to slow gut motility. Those with higher histamine, acetylcholine, and/or serotonin generally will have faster gut motility but keep in mind it is more complex than this.
Low dietary salt intake can contribute to anhedonia and slow cognition.
If you know you have low cholesterol levels (confirmed by blood test), this may contribute to depression, anxiety, and other mood disorders. Eggs and meat, especially fatty meat and organ meats are the best sources of cholesterol. Increased intake of fructose may also increase it.
Excessive methyl donors such as TMG can sometimes lead to very vivid dreaming for an unknown reason but may have to do with increased expression of acetylcholine and glutamate receptors, melatonin and its interactions with other neurotransmitters. Large doses of niacinamide comparable to the doses used of the methyl donor seems to fix this.
Even though heme-iron supplements cause less gut-related side effects, because the actual percentage absorbed is so low due to saturation of the absorption mechanism for heme-iron, if you want to fix nonanemic iron deficiency or ID anemia in a timely manner, higher doses of non-heme iron supplements such as iron bisglycinate are preferable.
Zinc has been shown to reduce the optimal dose for amphetamine by up to 37% at 30mg a day. This dose long term could pose an issue for copper status however. Zinc is likely important in reducing ADHD symptoms, so fixing a deficiency would be helpful.
Testosterone leads to hypomethylation of the vasopressin promoter (which means it increases vasopressin), which is likely how it reduces fear and anxiety like behaviors in male animals.
PGD2 is the most potent somnogen in man. Some things may reduce PGD2 synthesis if taken, especially late at night can contribute to insomnia. Selenium seems to be one of them.
Methyl donors, copper (with riboflavin for DAO), vitamin C, are known to be able to reduce histamine levels through enhancing deactivation by methylation and diamine oxidase. However this may not work all the time. Sometimes issues with deactivation are not the primary cause of histamine issues. It may help but not entirely.
The other issue could be overactive mast cells due to a lack of inhibitory signalling (mast cells stabilizers). Low adrenergic tone can increase mast cell activation, as well as too low cortisol. So for example copper and vitamin C not only are needed to deactivate histamine, but also are used to synthesize catecholamines which stabilize mast cells. Too low cortisol will also contribute to overactive mast cells. This is why epinephrine is used in medical situations to stop a severe allergic reaction as well corticosteroids used as long-term treatment for allergies.
This brings in to question the issue of caffeine (which enhances catecholamines) for allergies. Pure caffeine does generally help allergies because of this. Coffee can have worsening effects due to potential allergens in the coffee, so higher quality coffee would be preferred in regards to this. But whether is caffeine from beverages or caffeine pills, keep in mind that adaptation occurs which results in your own adrenergic tone being lower.
So if you skip a dose of caffeine that you normally would have, mast cell activity may increase because you have less catecholamine activity to inhibit them due to tolerance. If you are consistent with caffeine dosing (approximately every 5 hours of waking, due to half-life) it's not necessarily a problem. But getting off caffeine entirely will help allergies by restoring adrenergic tone which will no longer rise and dip throughout the day as caffeine levels in the system rise and dip throughout the day. Getting off caffeine may not help as much however if your adrenergic tone is too low due to some other reason.
