Biological Rhythm Disruptions and Adrenal Fatigue Syndrome – Part 3

By: Michael Lam, MD, MPH; Justin Lam, ABAAHP, FMNM; Dorine Lam, RDN, MS, MPH

Read Part 1 | Part 2

8. HISTAMINE Overload

Biological rhythm sufferers may be more sensitive to disruptions of neurotransmitters within the bodyHistamine is another neurotransmitter and this hormone plays a role in controlling our sleep–wake cycle. It is both a neurotransmitter as well as an immunomodulator. Depending on where it is found in the body, and what receptor it interacts with, histamine can elicit a multitude of reactions. There are four types of receptors, numbered H1 to H4. Each are found in different parts of the body and have distinctly different effects on the body’s biological rhythm when activated.

When our histamine levels are elevated we may suffer from:

  • Inflammation
  • Allergic reactions
  • Reduced energy production
  • Adrenal dysfunction
  • Increased food sensitivity
  • Gastric discomfort
  • Bloating
  • Inability to enter deep sleep
  • Awaken easily
  • Psoriasis

Histamine is usually metabolized in the intestines and liver. However, some individuals may have low levels of the required enzymes to metabolize histamine and thus have increased circulating histamine that can disrupt the body’s biological rhythm. Histamine is typically found in foods that have been fermented or highly processed. Fermented cheeses such as cheddar and Gouda are high in histamine. Other dairy products such as yogurt and buttermilk also contain elevated histamine amounts. Salami, pepperoni, sausage, and other processed meats are also high in histamine. Vegetables such as tomatoes, spinach, and eggplant contain increased histamine compared to other vegetables. Berries have been shown to be high in benzoates, which release histamine. Spices such as cinnamon, cloves, and nutmeg also contain benzoate and release histamine when ingested. These are usually not an issue because the body metabolizes them automatically without a problem.

Histamine-releasing neurons are located in the hypothalamus. From here, they project to all other brain areas. The neuron-firing rate varies across the sleep–wake cycle. The highest occur during waking and lowest during rapid eye movement sleep. Stress, dehydration, or hypoglycemia is typically experienced in advanced AFS. All three conditions trigger increased histamine release. Once released histamine activates four types of receptors. The central histamine system is involved in many central nervous system functions: arousal; anxiety; activation of the sympathetic nervous system; HPA axis hormonal system.

Dysregulated histamine balance can upset biological rhythm. Fortunately, excessive histamine in the body can be neutralized by quercetin and bromelain.

Quercetin can be considered the king of flavonoids. It is an excellent natural antihistamine that can help balance the body’s biological rhythm. It also interferes with the pain promoting inflammatory histamine that is generated in the body in many autoimmune diseases including rheumatoid arthritis and colitis. In addition to its antihistaminic effect, studies have shown that it is also able to fight off an enzyme that neutralizes cortisol, a natural anti-inflammatory chemical produced by the body. You can get quercetin by drinking more unfermented green tea as well as red wine. Apples, onions, tomatoes, green peppers, as well as broccoli are all excellent sources of quercetin. However, as a large amount of it is required to produce a positive effect, it is better to take a quercetin supplement.

Bromelain is an enzyme that is found in pineapple stems. Its primary activity is to reduce inflammation and promote healing, especially in muscles and joints. As such, it is popular and is used widely in sports medicine and trauma management. Bromelain’s anti-inflammatory property also plays a significant role in the management of asthma, arthritis, colitis, and other allergy responses. It should be noted that only high potency and high quality supplements should be used in a therapeutic setting. It should be taken on an empty stomach along with quercetin.

Biological Rhythm Rebalancing Principals

Rebalancing biological rhythm with Adrenal FatigueBiological rhythm disruptions may present classically as insomnia, but the underlying circadian disruption is a twenty-four seven phenomena. Restoring biological rhythm balance must start with understanding of the physiology behind the seven phases of biological rhythm during the day, starting in the morning and continues to bedtime. At each phase, specific steps need to be taken in terms of personalized supplementation, diet, and lifestyle modulations tailoring to each body’s specific clinical neurotransmitter volume, hormonal balance, receptor function, toxic load, body sensitivity, and assimilation capacity at that point in time to rebalance proper biological rhythm. The goal is to restore neurotransmitter balance to a state appropriate for that phase during that specific time of day to mimic the natural cycle as closely as possible.

Because most are already weak physically at this time from long standing insomnia, any biological rhythm rebalance has to progress slowly, especially in the beginning. Those who are in advanced stages of AFS are particularly vulnerable. Paradoxical or exaggerated reaction is common and has to be avoided. Expert close guidance and monitoring is required. Immediate adjustments are made in real time if possible. The rebalancing of the body’s biological rhythm process usually takes a few months in experienced hands.

Recovery tips through the Seven Daily Temporal BR Phases

Awakening Rhythm from 6 to 9 a.m. Some people wake up refreshed in the morning having had a good night’s sleep. Others wake up still tired, but begin to perk up after having breakfast and beginning their morning routine. Still others wake up refreshed, drag through this phase. Regardless of where you fall, the body can start its BR rebalancing effort in this phase

Increase energy using macro and micronutrition principles. Have a good breakfast when you wake up and start your day’s activities. NTs need to be on an excitatory bias to get your body moving. The BR should be clear of yesterday’s burden from the overnight rest. The body is fresh as we start the new day. Start with some Adrenal Circulation and Adrenal Restorative Exercises to help the biological rhythm. Nutritional supplementation with the right compounds is key to help the restorative process progress initially.

Recommendations for more energy in the morning:

  • Vitamin B6
  • Vitamin C
  • DHEA
  • Glutathione
  • Glycine
  • Pregnenolone
  • Amino acid such as arginine
  • Trace minerals
  • Iodine
  • Tyrosine
  • Vitamin B5 and pantethine
  • Vitamin D
  • Thyroid glandular
  • Adrenal cortex
  • Zinc
  • Selenium
  • Vitamin B12

Morning Rhythm from 9 a.m. to noon Your goal is to sustain your energy throughout the morning until lunch, while avoiding both anxiety and fatigue, which can occur in late morning as energy starts to wane and symptoms of hypoglycemia may appear. The overall neurotransmitter balance should become neutral as the awakening phase wears itself out.

Recommendations to support your bodily functions as you awaken continue. As the morning progresses, enjoy a relaxing cup of warm broth or a light nutritious snack during this phase to prevent any BR disruption from metabolic imbalance. Supporting the spleen at this time is important so you should have lentils or yams seasoned with cinnamon. Adrenal Yoga Exercise is recommended during this time. Adrenal Breathing Exercise is particular important in midmorning to tone down any excessive NT excitation carryover from the awakening phase, such as those taking in coffee, glandular, and stimulatory herbs like ashwagandha, rhodiola, maca, and ginseng.

There are many different symptoms associated with biological rhythm disruption.Anxiety has a tendency to surface in late morning. Any liver or extracellular matrix congestion can make matters worse. Supplement considerations should focus on neutralizing any excitatory NT tone as well as relieve liver and extracellular matrix burden. Combat this and stabilize your neurotransmitters with these:

  • GABA
  • Magnesium
  • Theanine
  • 5-HTP
  • Activated charcoal
  • Clay
  • High resistance water
  • Fermented milk thistle
  • Fish oil
  • NAC
  • Lipoic acid

Lunch Rhythm from noon to 2 p.m. Make sure that you have a good lunch with enough calories to sustain you through the entire afternoon. The food choice bias is towards more protein and fat and less carbohydrate. Salads with chicken are excellent choices for lunch. You should also supplement with the proper micronutrients, focusing on supporting continuous energy, preventing an imbalance in metabolism, which can bring on a food coma that occur soon after lunch and thus disrupted BR. Your NT balance should continue to be neutral and allow the nutrients from lunch to give you enough energy without depending on the excitatory neurotransmitters to start the afternoon activities.

Recommendations for this phase: It would be best to enjoy a nice relaxing lunch and take a twenty-minute power nap immediately thereafter. The heart doesn’t respond well to emotional or physical heat during this phase so we need to avoid:

  • Caffeine
  • Stress
  • Intense exercise
  • Anything that raises blood pressure

Afternoon Rhythm from 2 to 5 p.m. You need to support your energy flow in midafternoon and try to prevent any slumps in energy that could set off an alarm response causing an excessive release of norepinephrine and adrenaline and trigger an adrenal crash. Have an afternoon snack that includes complex carbohydrates. Take a twenty to thirty minute afternoon nap around 3 p.m. The NT balance should be a bit excitatory to make sure your body has enough reserve energy to sustain you throughout the afternoon if it’s not possible to take a nap. The net BR balance is maintained on a cruising mode.
Recommendations for sustaining you throughout the afternoon: It’s important to have a strong bladder during this time (for storing and secreting urine) and the bladder is nourished with salty foods so have a bowl of soup with a lot of liquid broth like miso or vegetable. This will keep the bladder and the kidneys (the paired organ) strong.

To combat an afternoon slump in energy and avoid metabolic imbalance:

  • Arginine
  • Chromium
  • Glutamine
  • Holy basil
  • Hydrolyzed collagen type 1 and 3
  • Milk thistle
  • Minerals such as marine phytoplankton
  • Amino acid such as arginine and glutamine
  • DHEA
  • Pregnenolone
  • Magnesium and theanine for anxiety carryover

Dinner Rhythm from 6 to 9 p.m. Gradually reduce your excitatory NT tone through dinnertime to ensure the smooth assimilation of food without any metabolic dysregulation, which could trigger an internal inflammation. Overall net your NTs should be slightly inhibitory in order to maintain a neutral BR, setting the stage for slowing down at the end of the day.
Recommendations for relaxing and easing into a sleep mode: You may take some time for meditation, reading, light stretching or cuddling.

Taking the proper nutrients can help balance the body's biological rhythm.To combat early evening anxiety:

  • 5-HTP
  • Fish oil
  • GABA in a low dose
  • Magnesium
  • Taurine
  • Theanine
  • Chromium

Those suffering from high cortisol at night should commence cortisol lowering with natural compounds that have a lagging effect such as phosphatidylserine during this phase. Continue Adrenal Breathing Exercises.

Sleep Onset Rhythm from 9 p.m. to 2 a.m. This is the time for the body to unwind. Your NTs should be moving towards a more inhibitory tone with acetylcholine acting as the main NT needed for the parasympathetic nervous system to maintain the proper state for digestion and rest.

Take a small snack rich in protein and fat right before sleep. Almond milk and nuts are excellent choices. This will help stabilize blood sugar and prevent metabolic imbalances that can occur a few hours later.

Recommendations to combat sleep onset insomnia:

  • 5-HTP
  • Arginine
  • Fish oil
  • GABA in small to moderate doses
  • Magnesium
  • Niacin
  • Passionflower
  • Phosphatidylserine
  • Melatonin
  • Progesterone
  • Fermented herbs such as valerian root
  • Vitamin D may be helpful for those with history of paradoxical reactions
  • Those with low cortisol can consider licorice and grapefruit juice
  • Those with high cortisol can consider phosphatidylserine (PS) and bioactive milk peptides. Bioactive milk peptides can be taken at bedtime, but PS should be taken a few hours before as well as at bedtime.

Sleep Maintenance Rhythm from 2 to 6 a.m. At this time, the body requires an ample supply of the needed inhibitory NTs, which combat any residual excitatory stimuli that may cause wakefulness during the night. The biological rhythm is prevented from stimulation. Metabolic imbalance can also cause frequent awakenings and your bedtime snack should be helpful in preventing this from triggering sleeplessness during this period.

Recommendations to combat sleep maintenance insomnia:

  • 5-HTP (time-release form)
  • Chromium polynicotinate (time-release form)
  • Melatonin (time-release form)
  • Glycine in high doses to saturate the body can be considered and taken at this time to support sleep for those with sleep maintenance insomnia.
  • Magnesium
  • Niacinamide
  • Passionflower
  • Taurine
  • Glycine
  • Inositol
  • Fish oil
  • Bioactive milk peptides

Proper timing of taking sleep aids is important. Glycine, for example, should be taken at bedtime and not at the time of awakening in the middle of the night because there is a lagging effect. We can also take advantage of time release forms of melatonin and 5HTP to their onset of action can be timed a few hours after going to sleep.

This phase is the most challenging because frequent awakenings and the inability to return to sleep is a sure recipe for fatigue the next day. Higher and frequent doses of supplementation and snacks throughout the night may be required. The Adrenal Breathing Exercise is very valuable at this time.

Five Reasons Why Self-Directed Programs Fail

A young woman troubled with biological rhythm disorder.Proper biological rhythm balance, especially in cases of severe insomnia, requires a comprehensive plan addressing the needs of each of the seven temporal biological rhythm phases of the day in order to maintain an overall daily rhythm that is natural, stable and consistent. This requires extensive clinical experience. Even in the best of hands, some trial and error is required due to the lack of accurate laboratory tests for guidance in addition to each body’s unique setting.

Many have tried self-navigating through a variety of natural compounds but failed to restore BR properly. Here are five common reasons for failure:

First, most are not versed in understanding the specific physiological pathway of each nutrient, resulting in the wrong choice. For example, taurine has NT inhibitory effects, but it is also a natural diuretic and increases excretion of water from the body. Taking it at nighttime may help sleep. However, it can also lead to increased awakenings due to frequent urination. Another example is 5-HTP. It tends to work better in the evening while GABA is better during the day. Proper selection of nutrient timed specifically for each phase will greatly enhance success.

Second, the approach of using targeted single nutrients works only in the mildest of cases. For example, melatonin alone may work well in early stages of AFS when biological rhythm disruption is mild. By the time biological rhythm is suspected in a setting of advanced AFS, insomnia is already well entrenched. Many have already been put on sleep medications by their physicians after failure of sleep aids. Different nutritional cocktails specific for the needs of each of the seven temporal biological rhythm phases of the day is usually required in order to reset the biological rhythm properly, especially in the beginning.

Thirdly, dosage requirements vary greatly from person to person. Melatonin at 3 mg may work well for one person but is completely inadequate for another who may do much better at a lower dose of say, 0.3 mg, or a higher dose of 30 mg. In other words, some compounds, like melatonin, are not linear in their dose response curve. More is not necessarily better.

Fourthly, certain compounds are more effective when taken by various delivery methods. For example, sublingual melatonin is more effective, especially in high doses, than capsules or pills because they contain less inert substances called binders and fillers required during the manufacturing process. Excessive binders and fillers can trigger vivid dreams and nightmares in those who have a sensitive pineal gland.

Lastly, proper timing is required to maximize the effectiveness of each natural compound. For example, the phosphylated form of phosphatidylserine (PS) is more effective to lower cortisol at night as compared to the nonphosphylated form. However, there is a four to six hour lag period from time or intake to bio activation. As such, it should be taken at dinnertime well before bedtime to be most effective.

biological rhythm can be rebalanced by A successful comprehensive protocol.In addition to the above five parameters, blind supplementation without considering to the constitution, stage of AFS, receptor site response, GI assimilation state, sleep medication dependency, extracellular matrix pollution and liver burden are common clinical mistakes resulting in improper dosage and clinical failure. A successful comprehensive BR rebalancing program is highly intricate and requires extensive clinical experience in both BR and AFS. Because dosage varies so widely from person to person, a detailed clinical history is key to assessing the right starting dose and combination of compounds. Most self-directed programs fail not because of the lack of tools but due to operator inexperience, resulting in a worsening outcome over time. Conversely, we are happy to report that most cases of BR and severe insomnia can be improved with natural compounds, when properly structured and executed.


Biological rhythm is a natural phenomena occurring in all healthy living mammals. Disruption can be caused by a variety of factors ranging from stress, neurotransmitter imbalance, and hormonal dysregulation. The classic presentation of BR disruption is insomnia. There are seven temporal BR rhythms during the twenty-four hour day. Their proper balance is critical to a healthy sleep cycle at night. Those suffering from chronic insomnia need to pay attention to these seven temporal phases for complete healing. Natural compounds are available to help, but few people are versed in understanding and planning a complete program to properly rebalance the BR. Thus, most self-navigation efforts fail. Yet with proper supervision and guidance, even the most severe cases of BR can find improvement.

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© Copyright 2016 Michael Lam, M.D. All Rights Reserved.

A balanced biological rhythm ensures a well rested morning