Author: integrativehealthpractices

IHP Aging and Health Optimization Program: Live Longer and Healthier

Over the past decade, a combination of research and clinical practice has created a basis for improving longevity and postponing illness such that quality of life is preserved as age advances.  The IHP Aging and Health Optimization program aims at helping you live longer with less illness and better functionality and quality of life through diagnostics and treatment based on the science and practice developing in this area.

The Program

In the IHP Aging and Health Optimization program, you will be given a menu of recommendations for diagnostics and therapeutics.  Some of these are available as part of conventional medical care, typically insurance-covered.  Others are based on evolving science or testing and interventions that are not generally considered medically necessary by insurers.  The decision to proceed with any of these diagnostics and therapeutics is entirely yours.  Your IHP practitioner will recommend them based on your unique history and assessment, and will work with you over a six or twelve month period to improve your potential for longevity and high function without chronic illness.

Recommended diagnostics may include:

• Metabolic, hormonal, inflammatory, and nutrient assessment using typically insurance-covered tests provided by LabCorp or Quest
• Biological versus chronological age assessment using methylated DNA and telomere assessment by a specialty lab
• Assessment by a specialty provider of body composition (fat and lean body mass), basal metabolic rate, and exercise fitness through VO2 max
• Cardiac risk assessment, including lipoprotein, metabolic, and inflammatory testing that is typically insurance-covered provided by LabCorp or Quest, and as needed CT coronary angiogram, using specialized imaging processing to stage coronary artery plaque
• Cancer early detection including typically insurance-covered GI, breast, and prostate screening and for high risk patients specialty lab-provided cell-free DNA pattern analysis
• Bone density assessment
• Brain/dementia/neurodegenerative disease assessment using cognitive, genetic risk, and NeuroQuant assessment based on the recommendations of Dale Bredesen, as well as amyloid imaging for patients with positive findings
• Functional strength and balance assessment to optimize physical performance and minimize injury/degenerative functional loss, provided in collaboration with Morrison Chiropractic

Recommended therapeutics, based on your diagnostic findings, include:

• Nutrients, supplements, and herbs—oral, liposomal, and IV— and prescription medications and hormones that address issues identified in assessment and diagnostics and promote improvement in aging hallmarks
• Nutritional/dietary changes to improve metabolic state and reduce risk or reverse chronic illness
• Exercise training, specific to your assessment, to optimize performance, improve fitness, strength, balance, bone density, and reduce potential for injury, provided by Morrison Chiropractic

Practitioners

All IHP physicians and PAs can guide current IHP patients in participating in this program.  Maria Shesiuk, PA-C is lead IHP program provider, and sees all new patients enrolling in IHP for purposes of the program.  Maria is a competitive weight lifter and certified yoga instructor, with deep interest and experience in fitness, diet, and integrative prevention and treatment of chronic illness.

IHP is pleased to partner with Morrison Chiropractic on the physical/musculoskeletal assessment and therapeutics that are included in this program.  Dr. Sean Nealon, DC is the lead Morrison Chiropractic program provider.  Dr. Nealon is an evidence-based chiropractor with experience as a personal fitness trainer. He is well versed in program design through his experience, his degree in exercise science, and his continuing education through organizations such as Functional Movement Systems, First Principles of Movement, Rehab-U, and StrongFirst. He loves training experienced fitness enthusiasts as well as people beginning their fitness journey.

If you are a current IHP patient with interest in this program, ask your physician/PA about it.  If you are not a current IHP patient but are interested, call us at 410-648-2555; you will receive a call back from one of our practitioners to discuss whether the program would be a fit for you.

The Evolving Science:  Aging Overview

Aging is a natural biological process that results from the interaction between environment/lifestyle and genetics. We are all born with genetic programming (both inherited from parents and transferred maternally as viral DNA and gut microbiome) that sets the direction for our biological development and decline.  Our genetics, however, are not solely responsible for our health and illness.  Genetics are modulated by life experience—diet, toxins, infections, physical activity and trauma, sleep, psychological and spiritual events—which profoundly affect our basic biological systems—digestive/absorptive, hormonal, energy producing, detoxification, immune, neurological/coordinating.  This interaction can result in health or illness over time.  As lifestyle is largely under our control, so is our ability to age in a way that increases lifespan and reduces functional decline and chronic disease.

Aging science is exploring ways of accomplishing this through research at two levels:  the ability to impact biological factors that vary as we age, and how we can modify lifestyle to favorably affect longevity and health.

The Evolving Science:  Aging Hallmarks

In 2013 Lopez-Otin et. al. proposed a conceptualization of aging based on nine biological factors referred to as “hallmarks” of aging, and in 2023 reviewed a decade of their use in research and added three factors to bring their number to twelve.  These hallmarks are both individually definable and intertwined.  Each must meet three criteria:  it must manifest with aging, experimental aggravation must accelerate aging, and experimental amelioration must retard aging.

Hallmarks of Aging

Genomic Instability	Nuclear and mitochondrial DNA is subject to damage over time; mechanisms for repair counteract this; preventing damage and augmenting repair may slow aging
Telomere Attrition	Telomeres are the end sequences of linear DNA; telomerases are needed to prevent incomplete replication during cell division resulting in telomere shortening over time; augmentation of telomerase activity may increase longevity
Epigenetic Alterations	DNA acts as the instructions for generation of proteins that are the basis for cellular and intercellular activity; protein generation is affected by epigenetic factors (DNA and histone methylation, chromatin remodeling) that can be enhanced or adversely affected over time and by environment with resulting impact on aging; proteins resulting from expression of selected sirtuin genes have been shown to increase longevity and stem cell regenerative capacity in mammals
Loss of Proteostasis	Protein/enzymes are responsible for cellular functioning; over time proteins may lose shape become damaged; promotion of autophagy (cleanup of damaged cellular structures) has been shown to extend longevity in mice
Deregulated Nutrient Sensing	Insulin and IGF-1 and MTOR reflect nutrient availability and are anabolic and associated with accelerated aging; AMPK and sirtuins reflect nutrient scarcity and are associated with increased longevity
Mitochondrial Dysfunction	Mitochondria are the energy-producing cellular structures and their numbers and function decline with aging; reactive oxygen species (ROS) and other other oxidative substances have the potential for mitochondrial damage but in small controlled amounts may have the opposite effect; telomerase and sirtuin activity may increase mitochondrial production; so may hormesis (fasting and small amounts of mitochondrial poisons including metformin and resveratrol)
Cellular Senescence	Cells become senescent with aging, but this may not have negative consequences as long as there is adequate autophagy of these aging cells; when not, inflammatory responses may predominate
Stem Cell Exhaustion	Stem cells provide the capacity for tissue regeneration; decline in stem cell populations occurs with aging; telomerase activation rapamycin
Altered Intercellular Communication	Intercellular signaling molecules, particularly associated with inflammation, often as a result of disordered nutrient sensing and senescence, accelerates aging; sirtuins and anti-inflammatory compounds may reduce this effect
Disabled Autophagy	Autophagy is the process of cleanup of cellular debris; increases in autophagy are associated with increases in longevity
Chronic Inflammation	Inflammation, often as a result of disordered nutrient sensing and senescence, accelerates aging; sirtuins and anti-inflammatory compounds may reduce this effect
Dysbiosis	With aging the gut microbiome is reduced in volume and diversity, which drives inflammation

Current research in this area focuses on understanding the relationship between these biological hallmarks and their impact on aging, as well as the identification of interventions that may ameliorate them with resulting increase in lifespan and postponement of chronic disease.  In the IHP Aging and Health Optimization program, we will recommend diagnostic testing and interventions based on these hallmarks.

The Evolving Science:  Lifestyle Factors

Aging shortens lifespan and negatively impacts functionality and quality of life through development of chronic diseases, including:

• Metabolic: diabetes, hyperlipidemia
• Cardiac and vascular: coronary atherosclerosis, stroke
• Brain: dementia, neurodegenerative, psychiatric
• Cancer
• Structural/Dynamic: low bone density/fracture and musculoskeletal degeneration/decline

Metabolic disease is both a direct cause of mortality and morbidity and key contributor to the other diseases.  Lifestyle drives metabolic and in turn other chronic diseases:

• Too much caloric intake results in increases in subcutaneous and visceral fat, with resulting insulin resistance and inflammation, which lead to vascular damage (atherogenesis) affecting the heart and brain, and compromised immunity (cancer), and musculoskeletal stress
• Dietary carbohydrate excess and protein and nutrient deficiency contributes to loss of muscle mass and bone density
• Insufficient exercise results in metabolic disease, loss of muscle mass/mitochondrial energy production and bone density, and predisposes to musculoskeletal injury

In the IHP Aging and Health Optimization program, we will recommend diagnostic testing and interventions to identify early, and prevent or reverse metabolic and chronic illness.

 

References

Attia, P. Outlive.  2023, Harmony Books. https://peterattiamd.com/outlive/

Fraser HC et.al. Biological mechanisms of aging predict age-related disease co-occurrence in patients.  Aging Cell 2022; 21:e13524  https://doi.org/10.1016/j.cell.2022.11.001

Langunas-Ramel FA and Bermudez-Cruz RM.  Natural compounds that target DNA repair pathways and their therapeutic potential to counteract cancer.  Front Oncol 2020:1-13.  https://doi.org/10.3389/fonc.2020.598174

Lopez-Otin C et.al.  The hallmarks of aging.  Cell 2013; 153: 1194-1217. https://doi.org/10.1016/j.cell.2013.05.039

Lopez-Otin C et.al.  Hallmarks of aging:  an expanding universe. Cell 2023; 243-278.  https://doi.org/10.1016/j.cell.2022.11.001

Schmauk-Medina T et.al.  New hallmarks of aging:  a 2022 Copenhagen aging meeting summary.  Aging 2022:14(16):6829-6839. https://www.aging-us.com/article/204248/pdf

Tsoukalas D, et.al.  Discovery of potent telomerase activators:  unfolding new therapeutic and anti-aging perspectives.  Molecular Medicine Reports 2019:20:3701-3708.  https://doi.org/10.3892/mmr.2019.10614

Bone fractures in people over fifty years of age cause significant disability, not only temporarily during the period of healing, but also over the long term – many people never regain their prior level of function following a fracture.  There is also a two- to four- fold increased risk of death in people over 50 with fractures.  Prevention of fractures is therefore important in increasing longevity and promoting healthy aging.

Bone is a dynamic structure, constantly being remodeled by cells that remove it (resorption by osteoclasts) and renew it (formation by osteoblasts).  In childhood the latter process predominates to support skeletal growth.  Once adulthood is reached, these two processes achieve relative balance, but over time the removal process typically predominates, particularly as hormone production declines around mid-life.  Predominance of resorption results in low bone mineralization and low bone density on DXA scanning, a diagnostic procedure in which the penetration through bone of a pair of xray beams is assessed.  DXA scans yield measurements of bone density, with results characterized as normal, low (osteopenia), or severely low (osteoporosis).  These results are used to predict fracture risk.

Although DXA scanning is the best method we have to predict fracture risk, it has a number of limitations:

• There is significant variability in results from different scanning devices. This can be minimized by having testing done (typically at two year intervals) in the same facility.
• DXA scanning measures bone density, but not bone strength. Strength is related to mineralization/density, but also derives from protein/collagen fibril structure and other architectural and material properties of bone.  Collagen is the scaffolding on which bone mineralization occurs, and enables it to bend, rather than break, under stress.
• Other factors, particularly age and risk of falling may be as or more important than bone density and strength in predicting fracture risk. For example, the same bone density in a fifty year old has a much greater fracture risk in an eighty year old.  Falls are a cause of 80% of fractures in elderly adults.

As a result, only about half of fractures in women and one quarter of fractures in men over the age of fifty are associated with low bone density.  Better predictions can be made by entering information into the online calculator (FRAX) that has been developed to include a variety of historical factors into the prediction algorithm.

It is common for patients to undergo DXA scanning, be told that their bone density is low, or that it is declining based on serial scans, and that as a result prescription medications are recommended to reverse the process of bone loss.  Although for some patients this may be appropriate – as when the risk of fracture is very high – for others it may not be for several reasons:

• Although medications have been shown to increase bone density, they have not been shown in controlled studies to reduce fracture risk. The most widely used medications (bisphosphonates Fosamax, Actonel, and Zometa; and Prolia) work by blocking bone resorption, which results in abnormal bony architecture which may make bones fracture-prone/brittle over time.  Like the bisphosphonates, there are no controlled studies showing reduced fracture risk from the PTH agonist Forteo.
• Medications are generally poorly tolerated (only half of patients prescribed them take them for more than a year), and there are some significant adverse effects including osteonecrosis of the jaw with bisphosphonates.

It is common for patients with low bone density to look for a non-medication approach to reducing fracture risk.  There are some studies that show that a couple of mineral supplementation regimens increase bone density, and in the past we have recommended nutrient supplementation with magnesium, calcium, Vitamin K2, Vitamin D3, strontium citrate, boron, and melatonin.  Of these, only three nutrients have been shown to not simply improve bone density but also to reduce the incidence of fractures; when used in combination, the reduction in vertebral fractures is as much as 60% and non-vertebral fractures by as much as 76%:

• Vitamin D3 – dosed to achieve a level of 30-50 ng/ml of the 25 hydroxy form
• Calcium – any form at a dosage of 500 mg per day
• Vitamin K2 in the MK4 form at a dosage of 22.5 mg twice daily (note that MK7 which is the other form of Vitamin K2 slows bone density loss but has not been shown to reduce incidence of fractures)

The role of strontium has been controversial.  In Europe, strontium ranelate is approved for treatment of osteoporosis, but in the US it has not been approved as it has potential for adverse cardiovascular effects. Instead, strontium citrate—which has not been associated with cardiovascular risk—has been recommended at a dose of 680 mg per day (taken hours apart from other mineral supplements).  Although the citrate form has been shown to increase bone density, there are no controlled studies showing its impact on fracture incidence.  Strontium has both weak anti-resorptive (bisphosphonate-like) and stronger bone formative (PTH/Forteo-like) effects.

In addition to nutrient supplementation, several other interventions are important in reducing fracture occurrence:

• Adequate daily dietary protein, e.g. 80+ g per day. This is important both to support collagen matrix contribution to bone strength, and to prevent age-associated loss of muscle mass, which is increases the risk of falls.
• Weight-bearing exercise, and exercise to improve balance and reduce fall risk
• Perimenopausal estrogen hormone replacement, which has been shown to reduce fracture incidence (testosterone supplementation in men may also be helpful, but has not been studied)
• Identification and treatment of other issues that may adversely affect bone health and functional activity levels – e.g. other nutrient deficiencies and heavy metal toxicity

Given the limitations of bone density screening, and the fact that it is recommended only at two year intervals, there has been interest in using blood testing to assess the balance of bone resorption and bone formation in between DXAs.  Two tests are currently used for that purpose – the C Telopeptide (CTP) which is a resorption marker and the procollagen type 1 N-propeptide (P1NP) which is a formation marker.  The use of these tests has not been studied as an adjunct to treatment to reduce fracture incidence.

Helpful resources are:

• John Neustadt, ND. Fracture-Proof Your Bones.  2022
• FRAX fracture prediction risk calculator: https://americanbonehealth.org/calculator/
• R Keith McCormick. The Whole-Body Approach to Osteoporosis. 2008
• Lani Simpson. Lani’s No-Nonsense Bone Health Guide.  2014
• Genuis SJ and Bouchard TP. Combination of micronutrients for bone study.  J Environmental and Public Health, 2012. http://downloads.hindawi.com/journals/jeph/2012/354151.pdf
• Sifat M, et al.Melatonin-micronutrients osteopenia treatment study.  Aging 2017. https://s3-us-west-1.amazonaws.com/paperchase-aging/pdf/vmFJfarchkyMAtwWn.pdf

Intravenous infusions provide levels of nutrients, herbs and other substances that are higher than can be attained with oral or liposomal supplementation.  These therapies can contribute substantially to the healing process in a number of the conditions that we treat.

Click ‘IV Therapies’ above to see brochure.

Energy-Based Healing

Most people who seek out integrative care are looking for an approach that goes beyond what is available in conventional medicine, but some are skeptical about the use of energy as part of the healing process.  The centerpiece of conventional medicine is the therapeutic use of prescriptions and surgeries, based on laboratory and imaging diagnostics.  For many people, integrative medicine widens the scope to include manual therapies – chiropractic, physical therapy, massage, and acupuncture – as well as nutrients, herbs, and supplements, aimed at addressing underlying causes and promoting our intrinsic capacity for health.  So why is energy-based healing needed?

In our view, for two reasons.

First, although we generally conceive of ourselves as physical beings that operate based on mechanical, biological, physiological, and biochemical principles, we at times acknowledge that there are other, nonphysical factors that impact our health.  Some of our diagnostics are energetically based – electrocardiograms, electroencephalograms, and nerve conduction studies for example – and there are therapeutics that derive from them in affecting electrical conduction through the heart and brain waves.  Additionally, psychological factors are widely accepted as important – often we talk about mind/body as a valid conceptualization of health.

We know less about, and tend to be less open to accepting therapies that are based on other energetic approaches.  The use of light/laser, sound, electrical current, and electromagnetic treatments are often at the boundaries of current health science.  Energy that is more subtle, perhaps conceptualized as spiritual, contributes to healing in ways that we know even less about.  Practitioners trained to appreciate such subtle energies, and gifted with the ability to detect and engage with them, offer something that is not otherwise available and is often overlooked in conventional and in some integrative practice.  The view of the world that is based on what is available to our physical senses is not sufficient to represent the deeper, inner aspects of our experience, and practitioners who can work in this more spiritual realm have much to offer.

Second, healing is a process that is not limited to curing disease and the signs and symptoms that it manifests, but also encompasses larger life experience.  People with serious illness – cancer in particular – often say that the illness changed their lives for the better by bringing them into deeper connection with spirituality.  People with illness affecting them in specific areas sometimes find that the illness is calling them to attend to the energy that is represented in that area – the heart as a focal point for love or the throat as a focal point for self-expression, for example.  Some patients join our practice unclear about why they have come; six months later, the reason that they sought us out has become obvious through the changes that have occurred in their life trajectory.

What is energy-based healing?  In our practice, it involves a consultation in which the practitioner helps the patient enter a state in which energy-based healing can occur.  This can be as a result of meditative quieting of the mind.  It can create energy flow through the chakra connections points between mind, spirit, and body.  It can facilitate identification and untangling of unconscious issues resulting from trauma and other negative life experience.  And it can bring healing energy in by uncovering connections between the inner soul and the archetypes, inhabitants, and universal energy of the spiritual world.

We regard energy-based healing as a core part of our integrative practice, and encourage our patients to access it as needed through consultation with Darcy and Heather.

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Background

Many patients present with illness that may be due to Lyme, other chronic infection, mold, or other toxicity.  Primary symptoms include fatigue/low energy, musculoskeletal or nerve pain, and cognitive and/or depressive/anxiety issues.  Related symptoms may be autonomic (palpitations, tachycardia, lightheadedness), mast cell/histaminic (congestion, itching, flushing, insomnia), or less commonly gastrointestinal (discomfort, bloating, heartburn, irregularity) or hormonal (thyroid, sexual).  There may be a history of Lyme, tick bite, other infections, mold or toxin exposure, either recent or in the past.  We generally do diagnostic assessment using standard (LabCorp or Quest) and where needed specialty lab and nonstandard testing, and based on that establish a tentative understanding of diagnosis and underlying causes, which is used to develop a treatment plan.  In doing this we face a couple of significant challenges.

The first is that there are typically multiple contributing causes to such illness, and lab assessment of them is not straightforward.  Some lab findings are pretty clear—low levels of nutrients or hormones, for example.  But other findings are often either equivocal—a Lyme test that has several positives but does not meet conventional criteria for positivity—or are of unclear clinical significance—Epstein-Barr or herpesvirus antibody positivity, mold toxin excretion or elevated metal blood levels.  Additionally, we don’t have testing available for issues that we’d like to better assess—healthy versus unhealthy immune system reactivity, mitochondrial dysfunction and causation, and immune or infectious activity in the brain.

The second challenge is that the treatment approach to such illness is often difficult to determine and implement successfully.  There are several reasons for this.  Most importantly, given that the causes of illness are multiple, treatment of one issue may not be helpful without treatment of others.  Additionally, the treatments themselves are not often backed up by strong evidence of effect—patients who have failed or seek alternatives to conventional treatments often need interventions that have not been clinically trialed.  Finally, some patients are quite ill or sensitive, and are only able to tolerate small, incremental treatment interventions.

Notwithstanding these challenges, our patients often improve through the course of our care.  But for some the improvement is less than they or we would like, and we are always on the lookout for new ways of supporting more powerful healing.

With that in mind, we constantly re-examine our approach to patients with illness of this type.  In this process we look at what is known about such illness, the evidence for various diagnostics and therapeutics, and what other practices are doing.  A description of our evolving approach follows.

Current Understanding

Chronic illnesses that involve infection and/or toxicity result from the interaction between the infectious or toxic agent and the host response.  Both sides of this interaction determine illness and resulting symptoms, and can be understood at a high level as follows:

• Infection/toxicity. We are part of broader ecology that includes micro-organisms and diverse plant and animal forms, many of whom predate and will likely outlive our species.  Some of this ecology lives within us – we are born with viral DNA and a gut microbiome, and following birth and for the rest of our lives we are exposed to and acquire toxins, viruses, bacteria, fungi, and parasites.  Some of these agents are beneficial to us—for example, the microbiome in our gut creates nutrients that we absorb and that affect our immune system and brain function in healthy ways.  Sometimes, however, these agents are harmful.  When a single agent produces acute illness, resolution may at times be achieved through conventional interventions to identify and eliminate it.  In chronic illness, on the other hand, the cause of symptoms may not be attributable to a single agent but rather to an imbalance between toxic and healthy agents that disrupt healthy function or trigger adverse host response, with symptoms that increase over time.  In such illnesses, treatment aims to restore balance among disruptive and healthy agents and host response.
• Host capacity for healing. We are also born with our own human set of genetic instructions.  Over time these instructions are modified (epigenetically) by exposures to infectious agents, toxins, traumas, diet, metabolic intermediaries, etc.  This results in an ever-changing capacity to respond to infection and toxicity through our detoxification and immune systems, and to produce energy at the cellular level. These systems are complex and intertwined, with subsystems that can be protective and beneficial in acute situations and when limited in scope but can be damaging to the host when they are uncontrolled or chronic.  Host response depends both on host systems (genetics, hormonal, metabolic, energetic, etc.) and the type and amount of the agent provoking the response.

Infectious agents and toxins vary in their own biology and effect on the host.  Lyme disease is classically an infection with borrelia burgdorferi, but may include infection by another strain of borrelia, by one or more coinfections, or by other infectious agents.  Although as a consequence treatment of Lyme may need to vary depending on the organisms involved, for the most part we don’t know as much as we need to about the differences in biology and effects of these organisms.  Here for example are some aspects of our understanding of the biology and effects of borrelia burgdorferi:

• The organism avoids oxygen-rich environments and is heat-sensitive, so may respond to oxidative and hyperthermic treatments
• Cell division cycle is long – 14-28 days – so treatment cycles likely need to be long
• The bacterium changes its structure to form cell wall-deficient forms that are resistant to some antibiotics, and antibiotic resistance also results from plasmid-mediated immunity, so treatment may require a combination of multiple antibiotics
• The infection is largely intracellular – in macrophages, epithelial cells, lymphocytes, fibroblasts – so treatment must include intracellular antibiotics
• When extracellular, the infection stimulates formation of biofilm that protects the organism from antibiotic treatment so biofilm disruption may be important
• The bacterium can successfully attack macrophages and lymphocytes including natural killer cells, compromising the immune response
• The infection promotes Inflammatory cytokine (IL-1, IL-6, IL-17, IL-22) chemokine, and toll-like receptor but not TNF alpha production, with short-term rise in CRP and inflammation in the central nervous system; the pattern of increase in these markers is variable across patients and may be responsible for damage to mitochondria, membranes, and myelin with resulting symptoms that may increase when antimicrobial treatment is undertaken
• The infection causes a shift in metabolism among immune cells away from mitochondrial oxidative phosphorylation toward glucose-based glycolysis (Warburg effect) and may be responsive to treatments that restrict glucose and shift metabolism from anabolic (mTOR) to catabolic (autophagy) states

As incomplete and complicated as this understanding is, it can be further complicated by the biology and effects of Lyme coinfections, or infectious agents, mold, and other toxins, about which we often know less.  For example, patients with persistent Lyme are often positive for blood markers and mycotoxin excretion that may be indicative of mold toxicity.  The clinical significance of this is variable, however.  The healthy human gut microbiome has been shown to include many species of mold (including fusarium, aspergillus, and penicillium) and factors such as diet influence the presence and amount of such organisms.  In some cases, these molds produce toxins that are associated with illness, but we don’t have an understanding of how and when this happens.

Despite this complexity and the limited state of our knowledge, two conceptualizations of host response to infection and toxicity are emerging that bear on treatment approach.

The first is Robert Naviaux’s concept of the cell danger response (CDR).  Naviaux proposes that there is a systematic, coordinated response to toxic and infectious threats to a host that aims to protect it by reducing energy production and energy-requiring activity but as a consequence results in chronic illnesses including chronic fatigue, autism and other neurologic/psychiatric conditions, autoimmune disease, and cancer.  The response is led by mitochondria, which are primarily known as organelles where cellular energy is produced but as importantly are lookout points for cellular threats and communication units that interact with the cell nucleus and with surrounding cells.   The response is triggered when a toxic “set point” is exceeded, can be amplified by subsequent toxic exposures, and does not abate until the threat is reduced or the system is reset.  It involves a shift from healthy winter (autophagy) to unhealthy summer (mTOR) metabolic state with multiple consequences for the cell and for host healing capacity including:

• Energy production via less efficient glycolysis rather than more efficient oxidative phosphorylation in the electron transport chain with decreased energy
• Increases in intracellular oxygen and oxidative damage that consumes cellular antioxidants such as glutathione, causing cellular damage
• Stiffening of cell membranes that degrade neurologic and energy production functions
• Release of ATP and other nucleotides that signal to other cells to make similar metabolic changes and stimulation of host-wide inflammatory response, dysbiosis, gut leakage/autoimmunity

Naviaux proposes that it is possible to reverse the cell danger response and attendant chronic illness through a healing process that reduces exposure to toxic agents (either the specific precipitating one or the many that comprise the toxic background) and by increasing the host capacity to handle and eliminate toxins.  He says that much of what must be done to accomplish such healing is still unknown, and that the healing process in chronic illness is requires months or more.

The second conceptualization is that of Thomas Seyfried, who is largely focused on a specific chronic illness – cancer.  Like Naviaux, Seyfried highlights the importance of mitochondria, arguing that cancer is a metabolic disease in which toxic or infectious damage to mitochondria causes a switchover to glycolysis rather than electron transport- driven oxidative phosphorylation, with resulting changes in expression of genes that promote or suppress oncogenesis, such at the p53 (tumor suppressive) gene.   His research rejects the prevailing view that cancer is caused primarily by somatic genetic mutations, which occur commonly, but instead depend on cytoplasmic metabolic changes.

Seyfried advocates for a ketogenic diet that restricts glucose in cancer patients while increasing the production of ketone bodies that can be used by non-cancer cells for energy.  He also advocates for pulses of cancer cell killing via oxidative treatments that increase reactive oxygen species in cells, which may occur alongside of conventional killing by chemotherapy and radiation.  Seyfried’s approach has been popularized by Nasha Winters who has explicated how it can be accomplished through diet and supplements, and Jane McLelland has expanded upon it with recommendations for use of supplements and repurposed prescription medications, including advocacy for an approach to oxidative killing that stimulates the Fenton reaction through ferroptosis.

Although the target of the Seyfried/Winters/McLelland conceptualization is cancer, it builds upon and addresses the Naviaux concept of mitochondrial injury and resulting metabolic and immune derangement.  As such, it provides a relevant approach to metabolically-based and oxidative therapeutics that may be applicable to infectious/toxic disease.  A challenge in all types of illness, however, is incorporate killing (cancer cells, microbes, toxin-damaged cells), without stimulating immune mediated damage to healthy host cells and resulting symptoms. Although much is known about innate and adaptive immune response, mediators (cytokines, chemokines, toll-like receptors), and helper cell Th1 and Th2 regulation, little is known about how to measure these aspects of host response in clinical practice and how to promote healthy response and repair or stimulate growth of damaged mitochondria.

Approach

Notwithstanding our incomplete understanding of the biology and effects of infections/toxins, there is need for a treatment approach that can be put into today’s practice.   Based on the understanding summarized above, we advocate for a multimodal approach that seeks to engage the host healing capacity and to reduce the infectious and/or toxic load.  Elements of this approach include:

• Enhance host healing capacity
  • Encourage health-promoting lifestyle practices: sleep, exercise, and purposeful, spiritual, conscious living
  • Address nutrient and hormonal deficiencies and imbalances identified through lab testing
  • Promote healthy gut microbiome and reduce gut leakage through avoidance of food allergens and provision of pre- and pro- biotics, gut nutrients and immunoglobulins
  • Optimize metabolism and encourage autophagy through increase in dietary protein and reduction in dietary carbohydrates, incorporation of periods of reduced dietary energy consumption, and use of autophagy-stimulating herbs and substances
  • Promote a balanced immune response using low dose naltrexone, herbs, energetic treatments
  • Promote mitochondrial health and healthy aging through herbs and other substances
  • Promote detoxification and drainage systems through herbs and homeopathics
  • Address dysautonomic and mast cell activation and toxic effects through vagal and brain training, acupuncture, herbs and substances
• Reduce microbial load
  • Reduce environmental sources of toxicity – mold, radiation, etc
  • Use antimicrobial and medication and herbal regimens to kill pathogens and reduce biofilm
  • Use oxidative and energetic treatments to kill pathogens

References

Bernardino ALF et al. Toll-like receptors:  insights into their possible role in pathogenesis of Lyme neuroborreliosis.  American Society for Microbiology

Infection and Immunity Volume 76, Issue 10, October 2008, Pages 4385-4395

https://doi.org/10.1128/IAI.00394-08

Buhner SH.  Plant intelligence and the imaginal realm.  2014, Bear and Company publishers

https://www.simonandschuster.com/books/Plant-Intelligence-and-the-Imaginal-Realm/Stephen-Harrod-Buhner/9781591431350

Hallen-Adams HE, Suhr MJ. Fungi in the healthy human gastrointestinal tract. Virulence, 2017:8:3, 352-358, https://doi.org/10.1080/21505594.2016.1247140

Harris, Steven.  Non-antibiotic approaches to the management of Lyme disease and co-infections.  2013:  https://www.acimconnect.com/Portals/0/Events/Dallas%202013/Presentations/Harris-%20DFW%20June%202013.pdf

McClellan, Jane.  How to starve cancer and then kill it with ferroptosis.  2021:  https://www.howtostarvecancer.com/product/how-to-starve-cancer-second-edition/

Naviaux RK.  Metabolic features of the cell danger response.  Mitochondrion 16 (2014) 7–17: http://dx.doi.org/10.1016/j.mito.2013.08.006

Naviaux RK.  Metabolic features and regulation of the healing cycle—A new model for chronic disease pathogenesis and treatment. Mitochondrion 2018. https://doi.org/10.1016/j.mito.2018.08.001

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Bone is a dynamic structure, constantly being remodeled by cells that remove it (osteoclasts) and renew it (osteoblasts).  Once adulthood is reached, these two processes should stay in relative balance, but as hormonal status changes over time, the removal process predominates.  For some people, hormonal-mediated bone removal may be predated or augmented by other conditions.

Predominance of bone removal results in low bone density (sometimes referred to as osteopenia).  When bone density declines, the structure of bone is altered and it loses some of its strength and flexibility.  Severe bone loss is referred to as osteoporosis; osteoporotic bone has thinner outer cortex and trabecular supporting structure.

Low bone density and osteoporosis are associated with increased risk of fracture.  Other factors, however, are also important in predicting fracture risk:  age, smoking status, body size, alcohol use, etc.  The FORE Fracture Risk Calculator (https://americanbonehealth.org/bone-health/introducing-the-fore-fracture-risk-calculator/) can be used to calculate fracture risk.  Importantly, the radiographic assessment of bone density by DXA scanning, which is the most widely used method of predicting fracture risk, does not take into account all of the factors that are relevant to this prediction.  The quality of bone (how it is structured and what its mineral composition is), as well as its density, is also important.  Bone quality is not generally assessable through non-invasive testing.

It is common for patients to undergo DXA scanning, be told that their bone density is low, or that it is declining rapidly based on serial scans, and that as a result prescription medications are recommended to reverse the process of bone loss.  Although for some patients this may be appropriate – particularly when the risk of fracture is very high – for others it may not be for several reasons:

• DXA scanning is subject to error, particularly if the patient is not properly positioned during the scan
• Factors that are causing the imbalance of bone resorption and bone renewal have not been identified and addressed
• Risks resulting from the use of the medications may be significant, particularly with bisphosphonates, which are associated with osteonecrosis of the jaw, and with spontaneous fractures owing to their effect on bone, which is to block the removal process such that bone formation predominates, which increases bone density but alters its quality (making it structurally more brittle).

When a DXA scan shows low bone density, it is appropriate to do lab testing to assess for conditions that are associated with bone loss (imbalance between removal and renewal).  Testing includes the general assessment that we use for most patients in integrative care (for hormonal status, nutrients, gut health/celiac status, and inflammation), as well as assessment of factors that are more specific to bone, including PTH, serum calcium, Vitamin D levels, 24 hour urine calcium, C Telopeptide (CTX) and osteocalcinin.  The latter three factors assess balance between bone removal and renewal, and are used in initial assessment of causes of low bone density and to monitor impact of treatment over the short run, with biannual DXA scanning and fracture risk prediction over the long run.

There are multiple causes of low bone density from imbalance between resorption and formation of bone:

• Nutrient deficiency, either dietary or due to poor absorption from the gut
• Hormonal imbalance: hypothyroidism or its overtreatment, hyperthyroidism, hyperparathyroidism, insufficient or excess insulin/diabetes, low growth hormone/IGF-1
• Chronic inflammation and oxidative stress: infection or leaky gut-based
• Heavy metal toxicity: cadmium, lead, mercury, aluminum, iron

The approach to treatment is as follows:

• Healthy diet and weight-bearing exercise
• Nutrient supplementation with magnesium, calcium, Vitamin K2, Vitamin D3, strontium, and trace minerals
• Address issues identified through history and diagnostic testing: nutrient deficiencies, hormonal gut health, inflammation/oxidative stress, heavy metal toxicity

Helpful resources are:

• R Keith McCormick, “The Whole-Body Approach to Osteoporosis,” 2008
• Lani Simpson, “Dr. Lani’s No-Nonsense Bone Health Guide,” 2014
• Genuis SJ and Bouchard TP, “Combination of Micronutrients for Bone Study,” J Environmental and Public Health, 2012: http://downloads.hindawi.com/journals/jeph/2012/354151.pdf
• Sifat M, et al, “Melatonin-micronutrients Osteopenia Treatment Study,” Aging 2017: https://s3-us-west-1.amazonaws.com/paperchase-aging/pdf/vmFJfarchkyMAtwWn.pdf