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Parkinson's disease is a debilitating neurodegenerative disorder that affects more than one million Americans each year, a figure expected to rise due to aging populations. The main characteristic feature of Parkinson's disease is the progressive destruction of dopamine-producing cells in the substantia nigra region of the brain where dopamine is made. This loss of dopamine production affects the communication between the brain and the body, causing muscle rigidity and tremors.

Present treatments for Parkinson's disease are limited to replacing dopamine in the brain as well as specific medications designed to slow the progression of the disease. Recently, researchers have demonstrated the role of oxidative stress and its impact on the brain in the Parkinson's disease process. This oxidative stress lowers glutathione levels, resulting in an increased demand for glutathione to help reduce the oxidative damage to the neurons.

According to a study published last month, researchers demonstrated that n-acetyl-cysteine (NAC), a precursor to glutathione, positively affects the dopaminergic system in Parkinson’s disease patients, resulting in positive clinical effects.

In this study, patients with Parkinson's were divided into two groups. One group received a combination of oral and intravenous (IV) NAC for a three-month period. These patients received 50mg/kg NAC intravenously once per week and 500mg of oral NAC twice daily on the non-IV days. The other group received only their standard Parkinson's treatment. Patients were evaluated by standard clinical measures including the Unified Parkinson's Disease Rating Scale (UPDRS) and a brain scan (DaTscan SPECT imaging), which measures the amount of dopamine transporter in the basal ganglia. The patients receiving NAC had improvements of 4-9% in dopamine transporter binding as well as 14% in their UPDRS score.

The study showed that patients receiving NAC improved both mental and physical abilities with brain imaging studies that tracked the levels of dopamine. This demonstrates that NAC may have a unique physiological effect on the brain that alters the disease process and may improve the function of dopamine neurons, offering a new approach for managing patients with Parkinson’s.

Glutathione is an important antioxidant which has been found to be depleted in the brain of Parkinson’s disease patients.  In addition, the extent of glutathione depletion appears to mirror the severity of the disease and is the earliest known indicator of degeneration. The brain has difficulty handling significant amounts of oxidative stress due to the presence of polyunsaturated fatty acids and low levels of antioxidants such as glutathione. In conclusion, providing antioxidant support with NAC or glutathione can provide a beneficial effect in Parkinson’s patients as well as with other neurodegenerative disorders. Additional nutrients that may be beneficial include CoQ10, fish oil, vitamin B12, tyrosine, phytocannabinoids, and Macuna pruriens.

By Michael Jurgelewicz, DC, DACBN, DCBCN

Source: Daniel A. Monti, George Zabrecky, Daniel Kremens, Tsao-Wei Liang, Nancy A. Wintering, Anthony J. Bazzan, Li Zhong, Brendan K. Bowens, Inna Chervoneva, Charles Intenzo, Andrew B. Newberg. N-Acetyl Cysteine Is Associated With Dopaminergic Improvement in Parkinson's DiseaseClinical Pharmacology & Therapeutics, 2019; DOI: 10.1002/cpt.1548

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It’s not uncommon to hear someone announce that they always feel cold. While some of us may think cold sensitivity is no more than a genetic predisposition or a result of being too thin, it could actually be a sign of a deeper health problem.

Body temperature and thermoregulation isn’t a subjective feeling; it is one of the most important functions of the central nervous system involving complex pathways that rely on the accuracy of peripheral sensor nerves, communication between the peripheral and central nervous system as well as the central nervous system and other organ systems, and correct thermoregulatory responses of organ systems. Multiple feedback and feed-forward systems are involved in thermoregulation and responsible for initiating both physiological and behavioral responses.

The body’s thermoregulatory responses can change not only in response to external stimuli (such as cold or hot weather) but also in response to internal stimuli. For example, the presence of an infection, stages of sleep, and energy and fluid homeostasis can all affect the body’s thermoregulatory response, independent of external temperatures.

Therefore, when someone feels chronically cold, it may be a sign of an internal problem rather than uncomfortably cold external temperatures.

Sleep Deprivation

Many of us have experienced the feeling of “being cold” when we are tired. Chronically feeling cold can be an indicator of sleep deprivation – an occurrence that is far too common with our modern lifestyles. Sleep patterns are associated with fluctuations in skin temperature gradients and prolonged sleep deprivation has been linked to progressively lower core body temperatures, even in the presence of increased food and energy intake (which generally raises core body temperature). In a human study seeking to determine the effects of sleep deprivation on skin temperature gradients measured over the entire human body, it was found that sleep deprivation created a significant dissociation between skin temperature gradients, increasing the activation of heat loss mechanisms in the lower extremities while stopping heat loss activation in the upper extremities. It was found that sleep deprivation disrupts the coordinated control of skin blood flow of the hands and feet by the sympathetic nervous system.

Anorexia Nervosa

Many eating disorders such as anorexia nervosa are not discovered except through unexplained symptoms that are recognizable only to the experienced practitioner. Feeling cold most of the time is one such sign of a potential eating disorder. As the body mass index decreases due to self-induced starvation, endocrine systems are disrupted and one of the primary outcomes is seen in the body’s thermoregulatory system and skin surface temperatures. In a study comparing healthy young women to those diagnosed with anorexia nervosa, the mean body surface temperature was assessed at various locations. In anorexic women the mean temperatures of the abdomen, lower back and thighs were significantly higher and the mean temperatures of the hands were significantly lower than their healthy counterparts. The mean temperature of the hands, specifically, was directly associated with reduced anthropomorphic parameters.

Low Thyroid Function

Increased cold intolerance is a typical sign of either classic, subclinical, or secondary hypothyroidism. The basal metabolic rate is influenced in-part by the levels of thyroid hormones. Low levels of thyroid hormones reduce the rate of ATP production and consumption. Thyroid hormones are also partly responsible for the development and function of the thermogenic brown adipose tissue. On the other hand, in cold conditions, brown adipose tissue helps convert inactive thyroxine (T4) into active triiodothyronine (T3). Further, the production of mitochondria is fostered by high levels of T3, so low levels disrupt energy production. In a prospective observational study of 33 patients with subclinical or classic hypothyroidism, restoring normal levels of thyroid hormones resulted in significant improvement in their response to cold temperatures.

Hypoglycemia

Blood sugar also plays a pivotal role in thermoregulation and dysregulated blood sugars can lead to both cold and heat intolerance. Hypoglycemia (either as an independent condition or in a diabetic state) decreases body temperature, leaving the feeling of being cold. The body’s response of lowering its temperature in response to a hypoglycemic state is independent of insulin levels as was shown in a study of 45 healthy men given various glycemic clamps and insulin infusions while measuring body temperature.

The feeling of being chronically cold or chilled could be a result of something as innocuous as being a female (who are known for having a lower body temperature as was discussed in a separate blog), having a lower body mass index, or simply spending your days in an air-conditioned building; however, before writing it off, consider the fact that cold intolerance could be subtly pointing to a deeper health concern such as a deficiency in sleep, food energy, thyroid hormones, or blood glucose.

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The fountain of youth. Books have been written about it, movies have been made about it, and billion-dollar industries have been built around it. Cosmetics and personal care items, exercise contraptions and slickly marketed “superfoods” all promise to deliver “anti-aging” effects. Biohackers jump on the latest diet and lifestyle trends related to longevity, hoping to eek out a few more years of existence. But is there really some merit to any of this, or is it mostly wishful thinking? Recent research from the University of Miami opens new avenues for exploration regarding human aging.     

While some people age gracefully, physically and mentally, and with all their cognitive faculties intact, these enviable specimens seem to be in the minority. For a larger portion of the population, healthspan decreases as lifespan increases—that is, as we age, we experience debility and decrepitude at a faster rate. A study published last month in Aging Cell, called “Longevity‐related molecular pathways are subject to midlife ‘switch’ in humans,” has uncovered information as to why this may happen. The findings are interesting because the research was conducted in human cells, whereas the majority of longevity research has been conducted in yeast cells, fruit flies, mice, worms and other short-lived or lower-order organisms.   

Researchers found that the human brain and skeletal muscle cells studied had an endogenous “program” that contributes to regulating the aging process. Protective mechanisms are in place during the earlier part of life, but according to study co-author Claes Wahlestedt, MD, PhD, “humans appear to stop using these pathways from about 50 years of age onward. Therefore, how long and how ‘hard’ each person regulates these pathways may influence human lifespan.” Dr. Wahlestedt noted that the most validated “anti-aging” programs uncovered in lower organisms are indeed active in humans, but for unknown reasons, something puts the brakes on these in the sixth decade of life.  

The intersection of lifespan and healthspan may be related to “nature versus nurture” or genetics versus lifestyle and environment. Everyone knows someone who smoked, enjoyed alcohol a bit too much, partied hard, and died at an old age in relatively good health. And we also know people who ate well, exercised, went out of their way to prioritize their health, yet developed an illness and died young despite their efforts to do the opposite. There may well be a genetic component to this—long and healthy lifespans often run in families—so it’s not possible to control all aspects of aging—unless you can pick better parents! But the study findings suggest we might have some control.

The Miami study found that as much as two-thirds of molecular aging in humans is explained by the mTOR protein complex (mammalian target of rapamycin) and by production of mitochondrial reactive oxygen species. mTOR is a key regulator of numerous processes involved in metabolism and aging, including cell growth and proliferation, autophagy and mitochondrial biogenesis. Chronic activation of mTOR may inhibit mitochondrial biogenesis and autophagy, potentially contributing to the progression of cancer and type 2 diabetes. Reactive oxygen species can cause chain reactions of damage to structural cellular and mitochondrial lipids and proteins, potentially accelerating the aging process. People are only as young as their mitochondria.

mTOR is a “nutrient sensor.” It’s “the master regulator of a cell’s growth and metabolic state in response to nutrients, growth factors and many extracellular cues.” It is upregulated by consumption of proteins and carbohydrates (especially simple sugars), so we can think of it as signaling that the body is in a “fed” state. In the current overfed dietary landscape of the industrialized world, this may result in obesity, non-alcoholic fatty liver disease, type 2 diabetes and other chronic metabolic diseases. Reducing food intake reduces mTOR activity and this reduction may be responsible in part for the increased lifespans observed in experimental animals subjected to fasting or caloric restriction. Owing to its multiple roles in cell signaling, inhibition of mTOR is highly promising as a therapy for numerous issues beyond diabetes and obesity, such as neurodegenerative disorders, cognitive decline, kidney disease and cancer.

Insulin and insulin-like growth factor-1 (IGF-1) are also major players in nutrient sensing. Chronic over-secretion of insulin is at the heart of metabolic syndrome and its associated comorbidities, which can certainly accelerate the aging process. Lower levels of these hormones are associated with better health and increased lifespan in model organisms. Insulin responds to numerous inputs but one of the most potent is refined carbohydrate. High-sugar diets are known to increase production of reactive oxygen species (ROS), so for healthy aging, a reasonable strategy might include caloric restriction across the board with an emphasis on restriction coming primarily via lower carbohydrate intake. (Indeed, the presence of the ketone bodies beta-hydroxybutyrate and/or acetoacetate has been shown to reduce production of mitochondrial ROS and increasing activity of antioxidant enzymes.)

While much is known about signaling pathways that influence aging in select organisms, human research is in its infancy. If there is indeed a genetic “switch” that flips somewhere around the sixth decade of life, there may not be much an individual can do to stop the aging process entirely or reverse it and actually get younger at the cellular level. But remaining metabolically healthy and maintaining cardiovascular and musculoskeletal fitness appear to be overarching ways people can stack the deck in their favor with an eye toward perhaps slowing the aging process and facilitating it happening more gracefully. 

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How often have you walked into a building and been irritated at the temperature which either left you with a cold-induced headache or heat-induced sweat? Or, have you ever found yourself in a work environment in which you and your coworkers get along great, except that you can’t agree upon the ideal temperature for the office? Maybe the battle for the thermostat takes place in your home. Nearly all of us have experienced uncomfortable indoor temperatures which have left us wondering how others can suffer through what we perceive as extreme cold or heat. According to researchers, the battle over the thermostat is not unfounded and is actually rooted in gender-specific temperature preferences. In a nutshell, women prefer higher temperatures and men prefer lower.

The average climate regulations for residential buildings and offices were developed in the 1960s and primarily based on the basal metabolic rate of the average adult male. Unfortunately, this estimation may be up to 35 percent greater than the average female basal metabolic rate. Women, therefore, are likely to feel uncomfortably cold in temperatures that seem well-regulated for men.

Effects on Cognitive Performance

According to a controlled study of 543 students, which sought to explore the effect of temperature on cognitive performance by gender, turning up the thermostat may help more individuals study and work more effectively. The study analyzed math, verbal, and cognitive reflective tasks in temperatures varying between 16.19 to 32.57°C (61.14 to 90.63°F). Results showed that females exhibited better performance in math and verbal tasks in warmer temperatures while males performed better in cooler temperatures. Neither gender showed differences in cognitive reflection tasks. Further, the improvement in the female’s math and verbal performance was more significant than the improvement in the male’s performance, suggesting that females are more sensitive to temperatures compared to males. Therefore, turning up the temperature may foster a more productive work environment; especially if the office has a substantial number of women.

Effects on Physical Performance

In a study published in Military Medicine, gender differences in thermoregulation were evaluated to determine the potential impact on physical performance. Women had a lower sweat output in response to heat stress and less shivering in response to cold stress, which indicated a greater difficulty regulating body temperature and a greater degree of sensitivity to temperature changes.

Physiological Differences in Thermoregulation

Past theories have led the majority to assume the gender differences in thermoregulation were due to physical characteristics such as women having less lean mass and muscle strength, lower body weight, higher body fat, and are typically shorter compared to men. These observations are certainly true and have an impact on thermoregulation; however, we now know that females also have a lesser ability to sweat due to possessing smaller sweat glands and a lower sweat output per gland. Therefore, men have a greater capacity to regulate body temperature through sweat heat loss. Similarly, women’s lower ability to shiver also suggests less power to generate heat. Finally, women tend to consistently have a lower skin temperature compared to men.

Further, the levels of various sex hormones affect thermoregulation and cause frequent fluctuations in a female’s core body temperature and response to external temperatures. A higher level of estrogen is associated with a lower body temperature since estrogen promotes vasodilation and heat dissipation. Progesterone has the opposite effect and is associated with higher body temperature.

Before using the research as evidence for cranking up the thermostat, just how much warmer do women prefer the temperature to be? Apparently not that much. According to one investigation, the mean comfortable temperature for women was 79. 3°F while men were comfortable at 77.5°F making the difference only a few degrees. Turning up the office or home thermostat just a couple of degrees may not only make for a more productive environment but has the added benefit of energy (and hence, cost) efficiency.

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With an avalanche of research questioning whether LDL cholesterol (LDL-C), independently of any other factors or biomarkers, plays a role in the etiology of cardiovascular disease, it’s hard to believe studies keep coming out trying to massage and manipulate data to support a hypothesis that is increasingly being abandoned. Nevertheless, this remains a very controversial topic, so it’s worth taking a closer look when one such study appears in a prestigious journal like The American Journal of Clinical Nutrition (AJCN). So let’s do that with a paper published just last month: “Effects of red meat, white meat, and nonmeat protein sources on atherogenic lipoprotein measures in the context of low compared with high saturated fat intake: a randomized controlled trial.”

The study the paper was based on—called the APPROACH trial (Animal and Plant Protein and Cardiovascular Health)—involved subjects 21–65 years old with a body mass index (BMI) 20–35 kg/m2 randomly assigned to a diet either high or low in saturated fat, and within those parallel arms, allocated to protein from red meat, white meat, or non-meat protein consumed for 4 weeks each in random order. Primary outcomes were LDL-C, total/HDL-C, apolipoprotein B (apoB), and small + medium LDL particles.

Results showed that, independent of the saturated fat content of the diet, LDL-C and apoB were higher after consuming red and white meat compared with non-meat proteins. Total/HDL-C was not affected by the protein sources, nor were small and medium LDL-particle counts. Researchers determined that the increase in LDL-C was due mainly to increases in large LDL particles—the ones believed to be the least atherogenic. (“Large buoyant” LDL particles make up the pattern A lipoprotein profile. It is not pattern A, but rather, pattern B—characterized by small, dense LDL particles—that is associated with cardiometabolic disease.)

Primary outcomes did not differ significantly between red and white meat. According to Ronald Krauss, MD, a co-author on the AJCN paper: “When we planned this study, we expected red meat to have a more adverse effect on blood cholesterol levels than white meat, but we were surprised that this was not the case – their effects on cholesterol are identical when saturated fat levels are equivalent.”

On the surface, this finding seems to suggest that red and white meat are “equally bad” when it comes to worsening cardiovascular risk factors. (What a disappointment to all the people who spent decades passing up juicy steaks in favor of dry chicken breast!) The title of the press release from The University of California even says they are “equally bad”—but it says they’re equally bad for cholesterol, not for cardiovascular disease. Having the same effect on cholesterol and this being a “bad” thing assumes increased LDL-C is independently causal for CVD or atherosclerosis. If red and white meat increase LDL-C to a similar extent, then they are “equally bad,” but if increased LDL-C is not automatically a risk factor for CVD, then neither is bad to begin with. (Indeed, serum LDL-C often does not correlate with actual arterial calcification. The coronary artery calcium scan may be a better indicator of the actual presence of atherosclerosis—the disease in place—compared to the amount of cholesterol in the bloodstream.)

It’s essential to note that all primary outcomes of this study are surrogate markers. They are not clinical endpoints. High LDL-C is not a disease. It’s not a heart attack or other cardiovascular event, and it’s being increasingly questioned whether it’s even a risk factor for these.    

Setting aside the protein sources for a moment, independent of protein source, the higher saturated fat diets increased LDL-C, large LDL particle count, and apoB compared to the diets lower in saturated fat. This might seem like a strike against saturated fat, but it’s certainly not news that consuming saturated fat tends to raise LDL-C. The part that’s up for debate is whether this is harmful for cardiovascular health—and many researchers assert that it isn’t. Some cardiologists have gone so far as to state outright that “saturated fat does not clog the arteries,” while other researchers have written that saturated fat is part of a healthy diet:

“Numerous meta-analyses and systematic reviews of both the historical and current literature reveals that the diet-heart hypothesis was not, and still is not, supported by the evidence. There appears to be no consistent benefit to all-cause or CVD mortality from the reduction of dietary saturated fat.” (Gershuni 2018)

The public has long been cautioned to reduce consumption of red meat and favor poultry, seafood and plant proteins instead. According to the UCSF press release, the study results “indicated that restricting meat altogether, whether red or white, is more advisable for lowering blood cholesterol levels than previously thought. The study found that plant proteins are the healthiest for blood cholesterol.” Again, this is based on the assumption that higher LDL-C is a causal factor in CVD, and it’s clear by now that numerous researchers and clinicians no longer believe that it is.

This is a topic that remains controversial and presents many unanswered questions. Healthcare professionals should continue to follow the science and strengthen and solidify their understanding of the biochemical and physiological mechanisms at work, rather than taking sensationalist headlines at face value. 

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The treatment of concussions and traumatic brain injury (TBI) is a clinical challenge. Medical treatments for post-concussion symptoms have consisted mainly of opiates for headaches, anti-depressants, anti-nauseas, anti-vertigo, stimulants, and other medications to increase neurotransmitter levels.

Previous research has demonstrated that athletes who wait to report a concussion may experience prolonged recovery times. Those who do not receive immediate treatment are at risk for further damage to the brain and will most likely take much longer to recover. Research indicates that intense physical activity during this vulnerable time immediately after a concussion can be detrimental.

In a new study published July 3 in Neurology, researchers investigated the effect of acute elevations in serum inflammatory markers and their association with symptom recovery following a sports-related concussion.

This study included 84 high school and collegiate football players, including 41 concussed athletes and 43 control athletes. Laboratory assessment included serum levels of interleukin (IL)–6, IL-1β, IL-10, tumor necrosis factor, C-reactive protein, interferon-γ, and IL-1 receptor antagonist. The Sport Concussion Assessment Tool, 3rd edition (SCAT3) symptom severity scores were also collected. These assessments were taken at a pre-injury baseline, 6 and 24-48 hours post-injury as well as at approximately 8, 15, and 45 days post-concussion. The total number of days athletes were symptomatic following the concussion was the primary outcome variable.

As a result, IL-6 and IL-1RA were significantly elevated in the concussed athletes at 6 hours relative to pre-injury and other post-injury visits, as well as compared to controls. Levels of IL-6 and IL-1RA significantly discriminated concussed from control athletes at 6 hours post-concussion. In addition, IL-6 levels at 6 hours post-concussion were significantly associated with the duration of symptoms.

These results demonstrate the potential use of these markers in identifying athletes at risk for prolonged recovery after a sports-related concussion.

Nutrient Considerations

Research supports early treatment of high dose omega-3 fatty acids in improving outcomes from TBIs. The brain needs to be saturated with omega-3s in order for the brain to heal. If these individuals do not have an optimal supply of EPA and DHA, healing will likely be impaired. In addition, there is no negative impact supporting these patients with optimal nutrition to regain as much function as possible.

Glycerophosphocholine (GPC) has also been used to help prevent damage to brain cells after blood flow, and thus oxygen, has been cut off to those cells.  GPC also supports the brain’s ability to recover after TBIs and helps reduce the symptoms associated with concussion and post-concussion syndrome. GPC is a form of choline that has been shown to protect and repair damaged brain cells.

Other supportive nutrients to consider include curcumin, magnesium l-threonate, acetyl-l-carnitine, phosphatidylserine, BCAAs, creatine, zinc, exogenous ketones and MCT oil.

By Michael Jurgelewicz, DC, DACBN, DCBCN, CNS

Source: Morgan E. Nitta, Jonathan Savitz, Lindsay D. Nelson, T. Kent Teague, James B. Hoelzle, Michael A. McCrea, Timothy B. Meier. Acute elevation of serum inflammatory markers predicts symptom recovery after concussion. Neurology, 2019; 10.1212/WNL.0000000000007864 DOI: 10.1212/WNL.0000000000007864

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What is geranylgeraniol? Geranyl-what? Besides being a bit of a tongue-twister, geranylgeraniol (GG) is a compound synthesized endogenously in the human body via the mevalonate pathway—the same biochemical pathway by which cholesterol, heme A, dolichol and ubiquinone (CoQ10) are synthesized. GG also occurs naturally in certain foods (such as flax, sunflower and olive oils, as well as select medicinal herbs), but the majority is synthesized endogenously. GG is an essential building block for the production of CoQ10, vitamin K2 and testosterone, as well as for protein synthesis and modification. Synthesis of GG declines naturally during aging and is inhibited by the use of certain pharmaceutical drugs, namely, statins and bisphosphonates. Repletion of GG stores may help mitigate the damaging side-effects of these drugs.

Effect of statins on synthesis of GG and downstream products

Statin drugs exert their effects early in the mevalonate pathway (via inhibition of the enzyme HMG-CoA reductase), far upstream of where GG and its byproducts are produced. Synthesis of all compounds produced after this step may be reduced, which likely contributes to the neuromyotoxicity and mitochondrial toxicity of statins. Decreased synthesis of CoQ10 may result in depressed cellular energy generation via impaired mitochondrial respiration, and consequences of reduced GG synthesis may include decreased endogenous vitamin K2 production and poor protein synthesis and modification with cascading effects on numerous tissue systems. The exact mechanisms behind the myopathy and myotoxicity many statin users experience are not known for certain but it’s possible they result from inadequate synthesis of GG and, as a result, inadequate CoQ10. Researchers have stated that GG is “the principal target of statin-dependent myotoxicity,” and statin-induced muscle damage “is the result of a geranylgeranylation defect”—potentially due to an inadequate pool of GG.

Heme A and dolichol

Beyond statins’ effect on CoQ10, their role in decreased heme A synthesis may also disturb mitochondrial function. Heme A is an essential component of cytochrome C oxidase, or complex IV of the electron transport chain, one of the major regulatory sites for oxidative phosphorylation and mitochondrial respiration. Deficiency of cytochrome C oxidase enhances mitochondrial apoptosis in response to oxidative stress. In addition to those related to reduced CoQ10 synthesis, some statin side-effects may result from insufficient heme A synthesis disrupting mitochondrial structure and function and therefore, cellular energy generation.

Drugs that impair GG synthesis also may result in decreased production of dolichol, a major lipid component of human endocrine organs. Dolichol plays a crucial role in cell membrane structure and function, influencing membrane fluidity and permeability. Owing to its large volume, muscle tissue synthesizes 50% of total body dolichol, but dolichol is synthesized at high rates in the liver, kidneys and spleen, and has a high concentration in the pancreas, testes, and thyroid, pituitary and adrenal glands. It’s believed that alterations in the amount and structural composition of dolichol derivatives may contribute to the changed cell membrane properties observed in certain diseases.

Can GG help?

Animal models and cell studies show that given in combination with statins, GG increases mitochondrial respiration and restores ubiquinone synthesis without negatively impacting statins’ cholesterol-lowering effects. Administration of GG to statin-treated human neurons decreased expression of inflammatory markers and reduced mitochondrial damage, facilitating maintenance of proper mitochondrial structure and function. In human monocytes and liver cells, GG reversed mevastatin-induced reductions in ubiquinone synthesis and mitochondrial electron transport that typically lead to cell death, again, without impeding the drug’s cholesterol-lowering property for those who benefit from that. (However, it’s worth mentioning that a great deal of controversy exists around whether elevated LDL-cholesterol, independently of other factors, is a risk for cardiovascular disease and whether statins are a wise course of treatment.) Notably, addition of GG was more effective than addition of exogenous CoQ10 for attenuating these adverse effects, leading researchers to state that compared to ubiquinone, “Geranylgeraniol may be a more useful and practical means of limiting the toxicities of statins, without reducing their efficacy as cholesterol-lowering agents.”

Bisphosphonates and GG

Bisphosphonate drugs are another category of pharmaceuticals that interfere with endogenous synthesis of GG through the mevalonate pathway. The enzyme target of these drugs is farnesyl pyrophosphate synthase (FPPS) rather than HMG-CoA reductase, so the precise mechanism is different from that of statins. PPS is involved in the steps immediately preceding GG synthesis. A common result of nitrogen-containing bisphosphonate (NBP) use is osteonecrosis of the jaw (ONJ). Effective treatments for this are lacking, and GG has been identified as a potential preventive and therapeutic agent. Most of the research in this area has been done in rodents and cell cultures but results are promising.

GG was shown to reverse the effects of NBPs on reduced angiogenesis, which is speculated to be one of many mechanisms contributing to ONJ. GG has also been shown to reverse the negative effects of NBPs in human fibroblasts, osteogenic cells and HUVEC cells. Endothelial progenitor cells (EPC) co-treated with NBPs and GG showed significantly increased cell viability, migration ability and increased EPC colony density (decreased apoptosis) compared to non-GG-treated controls, effectively reversing the negative effects of NBPs. Researchers concluded that systemic or local GG treatment could be a therapeutic strategy for ONJ. Similar results have been demonstrated for GG reversing the negative effects of NBP on human alveolar osteoblasts, periodontal ligament fibroblasts and oral keratinocytes. 

It’s ironic that the influence of NBPs on the mevalonate pathway may result in reduced vitamin K2 synthesis. Vitamin K2 is instrumental in supporting bone mass, so these osteoporosis drugs may actually induce the opposite of their intended effect. Vitamin K2-dependent enzymes play essential roles in calcium trafficking, and a deficit of enzyme activity may contribute to reduced bone mineralization and increased risk for vascular and soft tissue calcification. Although vitamin K1 accounts for over 90% of dietary vitamin K, the K2 form menaquinone-4 makes up over 90% of tissue vitamin K stores.

Future articles will explore other biological roles for GG. Evidence indicates it may be helpful for both acute and chronic pain relief, increasing testosterone and progesterone synthesis, and increasing insulin sensitivity, with implications for therapeutic use in type 2 diabetes—particularly in cases of statin-induced diabetes

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In an ideal world, we’d all be at the pinnacle of health—physically, mentally, emotionally and cognitively. We’d make all our meals from scratch, from whole-food ingredients purchased locally and in season. We would never fall ill, get injured, grow older, or go through anything else that might increase our bodies’ need for vitamins, minerals and other compounds beyond that which we get from food alone or that our bodies synthesize endogenously. But this is a far cry from the world we actually live in, and nutritional supplements can help ensure patients get what their bodies need for both acute healing and long-term health.

Many thousands of words have been written to make the case against supplementation, claiming that it’s “mostly useless” and “a waste of time and money.” The problem with these claims is that they expect supplements to be instant cures for chronic illnesses that result from poor diets and unhealthy lifestyles. Supplements are intended to be exactly that—supplemental to a nutritious diet. They’re not intended to undo or reverse the damage inflicted by daily dietary insult, sleep debt, sedentarism, drug or alcohol misuse, or anything else that can have an adverse impact on physiological function. So when studies assess a supplement—vitamin C, for example, or biotin, or manganese—and it’s determined that the supplement is no more effective than placebo for whatever the intended outcome was, it should come neither as a shock nor as a disappointment. Supplements can be powerful, but they’re not magical. They can facilitate and augment the body’s natural processes, but in the absence of any other dietary and lifestyle changes, they may not have as big an impact as they would if they were used as intended—as supplementary to the positive actions someone is taking for their health. There are numerous other issues that affect the need for and the efficacy of supplementation. Let’s explore a few of these.

Nutrient form and function

Some of the forms of supplements used in research may not be the most effective—for example, vitamin B6 given as pyridoxine, which may be less effective than pyridoxal-5-phosphate for certain applications. Studies looking at inositol for improving polycystic ovarian syndrome (PCOS) may employ only myo-inositol or D-chiro-inositol, when it appears that using both together may be more effective than either one alone. And of course, there’s the very controversial issue of supplementing with synthetic folic acid rather than natural folates. Using forms of nutrients that are less potent or less bioavailable may falsely indicate that the nutrients aren’t effective, but using a different form might have produced more promising outcomes.  

Therapeutic benefits for individuals with specific health conditions

People who are satisfied with their physical, mental and emotional health may not need supplementation, but considering that around 88% of Americans are metabolically unhealthy, most people probably can benefit from strategic supplementation targeted for their individual situation. For example, according to the Centers for Disease Control and Prevention (CDC), more than 100 million Americans have diabetes or pre-diabetes. Type 2 diabetes or insulin resistance may develop in part from deficiencies in specific nutrients needed for healthy glucose metabolism and insulin sensitivity (such as magnesium), but it also may cause increased need for certain nutrients, such as B vitamins and vitamin C. Diabetes may increase the need for essential fatty acids, because hyperglycemia inhibits the enzyme delta-6-desaturase, needed for elongating the essential fatty acids linoleic acid into gamma-linoleic acid (GLA) and alpha-linolenic acid into EPA and DHA. And diabetes is only one among a long list of common conditions that may increase the need for specific nutrients above that which people typically get from their diet, particularly if they have not yet transitioned to a healthier diet and lifestyle.

Pharmaceutical drugs influence nutrient status

Several pharmaceutical medications interfere with nutrient absorption and/or assimilation, resulting in deficiencies that may be correctable via supplementation. Various diuretics may cause increased need for potassium and calcium. Statin drugs are known to reduce synthesis of CoQ10 and vitamin K2, and metformin use results in reduced B12 absorption. These are just a handful of drug-nutrient interactions that affect nutrient status and may indicate that supplementation is warranted. It’s the rare patient these days who visits a doctor and doesn’t have a long list of medications they’ve been taking for years. These can cause clinically relevant deficiencies that should not be ignored, but rather, may be correctable in part by judicious supplementation.     

Dietary preference and aging

People following restrictive diets may benefit from targeted supplementation of nutrients known to be shortfalls on their particular eating plan. For example, vegetarians and especially strict vegans may require supplementation with vitamins D and B12, EPA/DHA, zinc and iron. Those following strict ketogenic diets may need more potassium and magnesium than they typically get from a relatively limited vegetable intake. Older people need more protein than they typically get from their diet in whole food form. For these individuals—especially those with dental problems or who may not be able to stand and cook for a significant length of time—protein powders and meal replacement shakes can be a convenient and effective way for them to get the nutrients they need.  

Nutritional supplements are not a panacea, but clearly, there’s an important role for them in numerous patient populations. From the patient perspective, however, it’s easy to feel like a deer in headlights in the middle of a health food store supplement aisle, totally overwhelmed by the sea of products on display. To ensure that they get the results they seek, rather than ending up with “expensive urine,” patients should work with qualified healthcare professionals to create a supplement regimen that will be effective for their desired goals.

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Smoothies seem to be a huge health craze as evidenced by the growth in smoothie franchises, chic smoothie cafes, and household devices that promise to make smoothie-making as smooth as possible. Even resolutions to eat healthier seem to be euphemisms for drinking more smoothies. With all the popularity and health claims that surround smoothies, it’s not at all surprising when individuals genuinely endeavoring to improve their health begin to question whether this new trend is as healthy as appears.

Before discussing smoothies, the terms must be defined. The term “smoothie” has been used to describe a wide array of items that are easy to drink, from protein drinks to blended fruit. For the sake of this blog, the term smoothie will refer to drinks with a blended base of fruit and/or veggies.

The question of whether smoothies are healthy is answered in another question, “What’s in it?” Smoothies can be a concentrated cup of healthy goodness or they can be a cup of disaster to one’s health. The outcome is contingent upon the ingredients.

Let’s first explore the potentially unhealthy components of a smoothie.

Sugar: The biggest potential health disaster in smoothies is the sugar content. The sugar load in a smoothie may not always be present in the form of added sugars. Instead, the source of sugar may be in the fruit – nature’s source of sugar as fructose. Smoothies (especially the commercially made variety) are notorious sources for an abundance of fruit. Fruit, alone, is certainly healthy, but hardly anyone would sit down and eat three to four pieces of fruit at one time. However, many smoothies are made primarily from fruit and it takes a larger quantity to fill a 16 to 20-ounce cup, increasing the amount of fructose the body metabolizes at one time.

Glycemic Index and Load: Perhaps the amount of sugar is not an issue, but what about its effects on blood glucose? One of the initial concerns with smoothies was whether ultra-processing fruits and vegetables which separated the components (namely, the fiber from the sugar) had an impact on the food’s glycemic index and load. A recent study measured the glycemic index (GI) and glycemic load (GL) of two commercial fruit smoothies to determine whether the impact of fiber was preserved. The results indicated that dietary fiber was retained and still positively influenced the glycemic response as indicated by a low GI and moderate GL. If fruit concentrates, fruit juices, or fractioned fruit are used in smoothies the fiber content will be eliminated, leaving a high GI and GL which will negatively impact blood glucose.

Macronutrient Balance: Drinking a cup full of fruit – even if a few veggies are added – does not provide a healthy balance of macronutrients. It provides a meal of carbohydrates, but virtually no fats and proteins to balance the metabolic effect of the carbohydrates. Further, studies showed that individuals who consumed smoothies that boasted of providing their daily need for fruits and vegetables were less likely to consume healthy, balanced meals and additional fruits and vegetables during the remainder of the day. Therefore, smoothies could become a “crutch” for consuming more unhealthy foods.

Nutrient Loss: Commercially prepared and stored smoothies may contain healthy ingredients, but processing procedures necessary for increasing shelf life are likely to damage some nutrients, lowering the antioxidant value. In one study of two fresh red vegetable smoothies based on tomato, carrots, pepper, and broccoli, there was a 2-fold loss in vitamin C following even a mild thermal treatment required to preserve the contents. Fresh smoothies impart the highest nutritional profile when consumed as soon as they are made.

Smoothies certainly can be a creative and convenient way to consume more fruits and vegetables. In turn, smoothies can help flood the body with additional antioxidants, micronutrients, and phytonutrients. However, some basic parameters should be followed to ensure smoothies are a concentrated cup of healthy goodness:

  1. Use vegetables as the primary ingredient of smoothies and add no more than two small pieces of fruit, for taste.
  2. Balance the macronutrient ratio by adding sources of healthy fats and proteins, including coconut oil, medium chain triglycerides (MCTs), nuts, seeds, and high-quality protein powders.
  3. Increase the health benefits by adding superfoods such as chia seeds, cacao nibs, turmeric, cinnamon, flaxseed, collagen, or chlorella.

And finally, don’t let your smoothie replace healthful meals throughout the day. Smoothies can be a great way to incorporate more veggies, boost antioxidants, and can be a medium for delivering extra protein and phytonutrients. However, smoothies must be viewed as vehicles for health; otherwise, they easily become high-sugar, fruit-based, milkshakes that wreak havoc on your blood glucose and metabolism rather than supporting optimal health and well-being. 

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Ear infections are among the most common reasons for visiting outpatient clinics. While most infections are caused by bacteria, otomycosis (otherwise known as fungal otitis externa) is a fungal infection. Fungi thrive in moist, warm environments and the ear provides an ideal location to lay down roots – or should we say hyphae. As the fungi colonize, itching, pain, aural fullness, aural discharge, hearing impairment, and tinnitus begin to plague the sufferer. Fortunately, the infection remains in the external ear canal, but occasionally, will move to the middle ear.

The offender most often belongs to the family Aspergillus, particularly Aspergillus niger; however, Penicillium, Fusarium, Mucoraceae, Scopulariopsis, Alternaria, Malassezia, and Candida have also been known to take up residence in the ear. Fungi are easily acquired while swimming, leading to a condition which has been colloquially termed, swimmer’s ear. Other means of gaining infection can include poor hygiene, living in humid or high-temperature climates, trauma to or inflammation in the ear, epithelial debris, and prolonged use of steroids (which depress immune function) or antibiotics (which disrupts the normal flora of the ear). Anyone with an impaired immune system or with conditions such as diabetes mellitus is at higher risk of developing otomycosis.

Conventional Therapy

Conventional treatments focus on antifungal agents such as azole group antifungals, amphotericin B, boric acid, mercurochrome and phenylmercuric acetate in sterile water, urea-acetic acid solution, or aluminum acetate solution. Unfortunately, resistance to common antifungal agents is becoming a concern and necessitating the discovery of alternative methods of treatment. In a study of 112 patients with otomycosis caused by one or two of 17 different fungal species, all mold species were found to be resistant to the common antifungal agent, fluconazole, and all yeast species were resistant to terbinafine. Further, 94 percent were resistant to itraconazole. Growing resistance may be a problem because fungi are difficult to eradicate (due to biofilms, high enzymatic ability, etc.), making recurrence and long-term use of pharmaceuticals common.

Alternative Therapy

Fungi are difficult to eradicate directly, making vigilant prevention a key to managing this condition. It is well known that immunocompromised individuals are at high risk for recurrent otomycosis; therefore, focusing on building and maintaining a strong immune system is vital. For individuals with diabetes mellitus, stabilizing blood sugar levels will be the single most important step that can help in maintaining a functionally effective immune system and keeping a healthy microbiome.

The microbiome of the gut is a large determinant in the robustness of an individual’s immune system. Further, the flora of the ear canal is also linked to the microbiome of the gut. Not surprisingly the most common infectious agent of otomycosis in immunocompromised individuals is Candida albicans, which is also the most common fungal species found in the gut and known to be associated with dysbiosis and other conditions represented by an unhealthy gut microbiome. Therefore, building a healthy gut microbiome is a foundational element of preventing recurrent ear infections such as otomycosis.

Garlic has been used for centuries as an effective antifungal agent. It has been studied specifically on Candida albicans and Aspergillus and found to be effective where pharmaceutical antifungals were not. Garlic oil was found to be able to penetrate the cell walls and various organelles of Candida albicans as well as modulate gene expression, downregulate proteins, disrupt metabolism, and prevent cell growth. Allicin, the most biologically active compound in garlic, has been shown to be more effective than garlic extract for inhibiting the growth of hyphae, making garlic effective against a wide variety of fungal species. Current research has not focused on the role of garlic in directly treating otomycosis; however, an older in vitro study with the goal of determining the efficacy of garlic in eradicating Aspergillus species associated with otomycosis found that aqueous garlic extract (AGE) and concentrated garlic oil both showed similar or better inhibitory effects than pharmaceutical antifungal agents.

In less humid/tropical climates, otomycosis is probably most often caused by moisture retention from swimming and identified as swimmer’s ear, but there are many other factors that make fungal ear infections common, even among non-swimmers. With rising resistance to antifungal agents, treatment of otomycosis can be difficult. The first line of action should focus on prevention through building a healthy immune system and being aware of the ideal conditions for fungal growth. But once the fungi start to flourish, garlic may be a good option for halting its progression.

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