Ellen Kamhi, PhD, RN, AHG, AHN-BC, is a leader in the herbal nutraceutical industry and is recognized as a consultant specializing in regulatory issues, formulation, and product education. She is a professional member of the American Herbalist Guild, nationally board certified as a holistic nurse, a medical school instructor in botanical pharmacology, and an author of many books. She offers online/onground continuing education-approved herbal certification programs, and she offers Ecotours for Cures (http://www.EcotoursForCures.com) to experience shamanic healing traditions in indigenous areas of the world. Her passions include sharing her 4 decades of herbal and nutritional knowledge with individuals that will carry natural healing arts forward into the next millennium. For more information, please visit http://www.naturalnurse.com/.
Interview by Craig Gustafson
Alternative Therapies in Health and Medicine (ATHM): How is the hypothalamic-pituitary-adrenal, or HPA, axis affected by gut dysbiosis?
Dr Kamhi: There are many ways that gut dysbiosis may negatively affect health and well being. Gut dysbiosis refers to an imbalance in the microflora of the intestines. It is actually a rather complex discussion, because certain organisms that might be considered dysbiotic in one person may actually be compatible to someone else. It is not necessarily one specific microorganism that overgrows versus another.
Microorganisms release a plethora of metabolites, including hormones and waste products, all of which can act as triggers to pathways and normal hormone production linked to the HPA axis within an individual. One example would be Candida albicans. It is a normal component of gut flora and usually exists without causing negative health issues, but it can also overgrow and cause the host individual to exhibit a variety of symptoms, such as gastrointestinal issues, bloating, diarrhea, constipation, skin rashes, tiredness after eating, and sugar cravings. Specific metabolic waste products are responsible for these symptoms, such as the neurotoxin, acetaldehyde, which is linked to “brain fog” and depression, typically experienced by those with a Candida overgrowth.
In addition, Candida and other yeast forms grow root-like structures called mycelia, which can interfere with gut integrity and literally “punch holes” in the gastrointestinal lining. These same phenomena can also occur in the oral cavity in gum tissue. Microbes travel through these fissures from the gums to other parts of the body and can lodge in the heart and other organs. The small fissures in the cell membranes also allow other larger particles that are normally confined to the gut to escape into interstitial serum and the circulatory system. This phenomenon—referred to as intestinal permeability, or “leaky gut”—is one factor that initiates an inflammatory response. Also involved in this inflammatory cascade are immune complexes, formed when the immune system attempts to destroy the large misplaced particle by attaching to it and, thereby, forming a “complex.”
Microorganisms actually release their own hormones, which can interact with hormones produced by the organs of the HPA axis—the hypothalamus, pituitary, and adrenal glands. Specific microorganisms have been shown to release hormones that might stimulate hunger centers in the brain, possibly causing sugar cravings. Our bodies normally have a hormonal system of checks and balances. There is a hormone referred to as fibroblast growth factor 21 , or FGF21, that is produced in the liver in response to a high carbohydrate level in our bodies. This hormone helps to suppress sugar craving signals from the brain. However, microorganisms need sugar for survival and growth. They use the available carbohydrate at a much faster rate than our body would on its own. That action decreases the production of FGF21 and, therefore, overrides the suppression of sugar cravings.
Through this and other mechanisms, dysbiosis interferes with normal HPA-axis homeostasis.
It is all an integrated system, where there is a huge interplay between the HPA axis and various hormones, some of which are just beginning to be discovered. For instance, orexin, also referred to as hypocretin, is a neurotransmitter that regulates arousal and wakefulness, as well as appetite. Orexin deficiency is involved in the interplay between sleep disorders and weight gain.
Orexin is produced by a few specialized cells in the hypothalamus. The axons from these neurons extend throughout the entire brain and spinal cord. Orexin is decreased by high levels of glucose. Levels can be supported by increased intake of amino acids, such as aspartate, alanine, serine, cysteine, and glycine. Stress converts these amino acids to glucose, thereby decreasing orexin and interfering with healthy sleep cycles. There is interplay between the stress factor, the inflammatory factor, and the gut dysbiosis factor, which are all linked to the complex interplay within the HPA axis.
ATHM: Is the interaction between bacterial hormones and the human system a specific adaption or a happy coincidence for the bacteria?
Dr Kamhi: It is difficult to discern whether this hormonal interplay is a specific adaptation or a happy coincidence. We certainly do know that microorganisms can definitely adapt. This is the same mechanism which can lead to the development of resistant bacterial strains, linked to the overuse of antibiotics. There are several mechanisms that are involved with this adaptation. One of these mechanisms is linked to the regulation of the multi-drug-resistant pump, or the MDR pump. Cells contain a mechanism called an MDR pump that recognizes “unknown” chemicals, such as an antibiotic, which stimulates the activity of the MDR pump to remove the chemical. Microorganisms have adapted this naturally occurring process to their own benefit. They become competent at upregulating the MDR pump, which then pumps the antibiotic out of the cell and the microorganisms are, therefore, able to survive.
As is often the case, natural substances can have an advantage over chemical pharmaceuticals. In the case of antibacterial substances, berberine is a naturally occurring alkaloid found in several botanicals, including goldenseal, barberry bark, and Oregon grape root. Berberine has been found to inhibit the action of the MDR pump. This leaves more of the antibacterial substance in the cell to kill bacteria. Perhaps that helps to explain why taking a natural antimicrobial agent that contains berberine does not lead to the development of resistant bacterial strains.
ATHM: You said that stress causes a cascade that converts amino acids to glucose. Considering its role as our stress compensation system, would you say that that particular process can turn the HPA axis against us?
Dr Kamhi: As is often the case, there is no clear answer to cover all situations, so it depends. Look at the particular activity of the various hormones related to the HPA axis. Let’s consider cortisol. Cortisol depresses the immune system and raises blood sugar—an adaptive mechanism often referred to as “fight-or-flight.” This is an immediate reaction to a threat and is actually advantageous to escape an immediately dangerous situation, and supports an immediate life-saving reaction if you have to run away from something really quickly. Cortisol also narrows the arteries, whereas epinephrine—released by the adrenal medulla—increases the heart rate.
The maladaptation to this same mechanism occurs when the spurt of cortisol does not turn off after a short period of time but rather becomes something that is ongoing. In a normal situation, the stress situation is resolved and the hormone levels downregulate back to normal. Long-term cortisol release does not allow the normal downregulation response. This leads to a variety of symptoms including sleep disturbances, migraine headaches, obesity, belly fat accumulation, thyroid dysfunction, digestive complaints, and leaky gut syndrome. This also leads to low energy, fatigue, low emotional states, and depressed immune function.
ATHM: What other endogenous factors impact the HPA axis?
Dr Kamhi: The HPA axis is complex, and I believe the term complex is actually an oversimplification. In addition to the hypothalamus, pituitary, and the adrenals, other glands, including the thyroid and pineal gland, are also involved. In my opinion, the pineal gland is too often left out of this discussion.
The pineal is incredibly interesting. If you look at where it is in the brain, it sits right near all of those other glands. The pineal secretes melatonin, which regulates the circadian rhythm cycle. The circadian rhythm describes 24-hour cycles in the body, such as the sleep cycle and temperature cycle. It is initiated by exposure to darkness and light, as well as interplay between all the hormones that we discussed previously.
The pineal gland is also recognized as a spiritual center throughout history and is often represented by a pine cone. This symbol shows up in ancient Egyptian artwork as the staff of Osiris, the Egyptian god of the underworld, and is also surrounded by the 2 serpents of the Kundalini, a common symbol found in Eastern practices. Biochemical human electrical energy can also be linked to the pineal gland. A common medical symbol is a staff with a solid center, which represents the spine, and a pine cone on top, which represents the pineal gland. It is also thought to facilitate altered states of awareness in those people who have had their “third eye” opened or are a seer. On a somatic level, it is interesting to note that the pineal gland rests behind the sphenoid bone where all of the fascia attachments gather, and every corresponding contraction initiated by external stimuli, such as a threat or reward, mechanically interacts with and squeezes the pineal gland, which then releases hormone messengers.
From a complete, natural-healing perspective, it must include references to the spiritual self, the emotional self, and psychological activity that is so intimately linked to not only the spiritual, but the physical as well.
Melatonin production occurs only when the pineal gland is influenced by the presence of darkness. Melatonin is also known as N-acetyl-5-methoxytryptamine. Its precursor is serotonin, or 5-hydroxytryptamine. There are many pharmaceutical therapies based on serotonin reuptake inhibitors, known as SSRIs.
As we investigate the mechanism of action of these drugs, I question the basic nature of this kind of medical intervention. While SSRIs do keep the serotonin in the nerve synapse for a longer period of time—because it downregulates the natural reuptake mechanism—in due course, this action leads to the serotonin being used up. It interferes with its natural replenishment. So, of course, these drugs only have a short shelf life in terms of how long they are going to be helpful.
It is so much better to look at how we can help our pineal gland manufacture and secrete more melatonin. We can accomplish this by assuring we have complete darkness, which can be challenging in today’s world. Also, providing building blocks, such as tryptophan, is useful. That is why 5-hydroxytryptophan, known as 5-HTP, is also used as an aid in sleep and relaxation. There are 3 wonderful herbs that can be helpful: fenugreek, spearmint, and fennel seeds. All 3 of these support the body’s ability to increase its natural production of melatonin.
Also, meditation is effective. If that sounds too Eastern and too mystical for some people, it can simply be prayer or another more Western approach called mindfulness. There is actually quite a bit of very good mainstream research measuring melatonin and serotonin levels, which are positively influenced by these relaxation techniques.
The discussion related to the importance of sleep is escalating in mainstream America. I think one of the big issues is light pollution. In our regular, daily lives, rarely does anyone go to sleep when it gets dark and wake up when it gets light. Most people are over-viewing computer screens, which emit a blue light that actually interferes with hormonal regulation. There are programs available for download, which lower the emission of blue light later in the day, to allow the melatonin cycle to initiate with less interference.
In parts 2 and 3, Dr Kamhi discusses a variety of specific herbs and how they can be used to support the organs of the HPA axis.