Jule Klotter

Brain Glymphatic Transport

Cerebrospinal fluid (CSF) circulates throughout the brain via spaces beside the arteries, exchanges with interstitial fluid, and exits along para-venous pathways to cervical lymphatic vessels, taking waste, such as soluble amyloid β, with it. Researchers are finding that body dynamics affect transport through this recently discovered brain-wide lymphatic system called the glymphatic pathway.

One factor that affects brain glymphatic transport, according to Hedok Lee and colleagues, is brain arousal level.¹ During sleep or anesthesia, the volume of the brain’s interstitial space expands significantly, lowering overall resistance to CFS in-flow. This decreased resistance facilitates the exchange between circulating CSF and interstitial fluid (ISF) and increases the transport of soluble wastes toward the cervical lymphatics.

In their 2015 animal study, Lee et al reported that sleeping position also affects the glymphatic pathway and waste removal from the brain. Body posture is known to affect cerebral blood circulation and intracranial pressure. Lee and colleagues used dynamic-contrast-enhanced MRI and kinetic modeling to quantify CSF-ISF exchange rates in anesthetized rodents’ brains while the animals were placed in supine, prone, or lateral positions. In rats, glymphatic transport was most efficient when the animals were on their side. In mice, the lateral and supine positions showed better transport than the prone. Anesthetized animals positioned on their stomach retained more of an injected tracer and lost significantly less of the tracer. While this study shows that sleeping position affects glymphatic transport, the specific results may not hold true for humans, given that human anatomy, physiology, and body size differ greatly from rodents. Also, anesthesia, used in this study, does not have the complexity of normal sleep with its many stages.

The authors note that cervical lymph vessels are surrounded by sympathetic and parasympathetic projections, “suggesting direct autonomic control of lymphatic drainage.” Venous return may be lower in the prone position, compared to the lateral and supine positions, leading to a decrease in cardiac stroke volume and increase in overall sympathetic tone and secretion of norepinephrine. Norepinephrine inhibits glymphatic influx.

Brain arousal and sleeping position are not the only factors known to affect CFS circulation in the brain and the glymphatic pathway. Inspiration drives CSF flow, according to a 2015 study.² Steffi Dreha-Kulaczewski and German colleagues used a novel MRI technique to track CFS flow in healthy human subjects: “We observed significant CSF flow exclusively with inspiration. In particular, during forced breathing [2.5 seconds inspiration, 2.5 seconds expiration], high CSF flow was elicited during every inspiration, whereas breath holding suppressed it. Only a minor flow component could be ascribed to cardiac pulsation.”

The combination of these two studies makes me wonder if deep breathing before sleep might enhance waste removal from the brain.

Vitamin C Treatment for Whooping Cough

“Whooping cough epidemics in the pre-vaccine era (that is, before the mid-1940s) occurred at two to five-year intervals and these cycles have continued in the vaccine era,” according to a 2012 Cochrane systematic review.³ Sultan M. Altuniji and colleagues add that the reported incidence of whooping cough has increased over the past two decades despite widespread vaccination. This highly contagious respiratory illness is particularly dangerous for infants. Conventional treatment for whooping cough is antibiotic therapy, but the Cochrane review of 13 trials involving 2197 patients found no evidence that antibiotic treatment improves “clinical course of the illness.”

Initially, as the bacteria Bordetella pertussis colonizes the lungs, whooping cough has the symptoms of a cold with fever, malaise, and coughing, explains Suzanne Humphries, MD, in her lay-friendly article “The Vitamin C Treatment for Whooping Cough.”⁴  When B. pertussis infects the ciliated (hair-like) epithelial cells of the respiratory tract lining, it secretes a cytotoxin that prevents the hairs from moving protective mucus and pathogens out of the lungs and towards the throat where it is swallowed. This toxemic stage of pertussis begins gradually with a cough that becomes progressively stronger and prolonged, as the body tries to expel mucus collecting in the lungs.

These coughing fits, which can occur at regular (even hourly) intervals, often end in a characteristic gasp (whoop) as the child sucks in air. Infants have a harder time coughing up the mucus that impairs breathing than older children and adults do. Older children do not tend to ‘whoop’ as much. Humphries says, “A classic way of diagnosis is to touch the middle of the tongue with your finger to see if this starts the cough….” Eating and running around can also trigger a series of coughs.

Since the pertussis vaccine does not guarantee protection against the disease and antibiotics do not change clinical course (and wreak havoc on the microbiome), are there other options? Humphries recommends ascorbic acid, a treatment used by Canadian physicians and researchers in the 1930s.

In a 1937 article for the Canadian Medical Association Journal, M.J. Ormerod, Byron M. UnKauf, and F.D. White explained oral vitamin C treatment using case reports.⁵ (They note that another researcher, T. Otani, had success using intravenous ascorbic acid to treat whooping cough.) Instead of bowel tolerance, the Canadians used urine acid levels to monitor ascorbic acid levels, the accepted means of monitoring vitamin C saturation at that time: “As treatment was begun the excretion of the acid rose, and when saturation of the tissues was complete there was a sharp well-maintained rise in excretion of the acid.” After some experimentation, they developed a routine daily dosage treatment, given in divided doses, of 350 mg on the first day, followed by 250, 250, 200, 200, 150, 150, 125, 125, and 100 mg (until symptoms disappeared) on succeeding days. They stopped treatment whenever symptoms had completely resolved for two days. “A patient on routine dosage who shows a sudden drop in urinary excretion, even when medication is taken, usually shows a corresponding change in the clinical picture,” the authors write. “The development of the whoop seems to use up a large amount of vitamin.”⁵

Unlike the Canadians of 80 years ago, Humphries recommends a daily dose of 375 mg of non-GMO sodium ascorbate per kilogram of body weight in divided doses.⁴ Liposomal vitamin C can be used to help stabilize ascorbic levels at night, if a child is not soy-sensitive; but the dosage needs to be adjusted as liposomal C is more potent than sodium ascorbate: 1000 mg of liposomal C is the equivalent of about 3000 mg of sodium ascorbate. “If your dose is right, within 8 hours there should be a two-third reduction in the coughing,” Humphries writes. “If you start to taper the vitamin C too soon, e.g., before four weeks, you could see an increase in cough. You will then have to go back up to the old dose.” A written record of symptoms helps caregivers keep track of changes. Humphries recommends cutting dosage by 50 percent if loose bowels occur.

Sugar (including honey) and simple carbohydrates compete with vitamin C transport into cells and should be avoided during treatment. Other foods that can slow recovery include dairy foods and sucralose-containing products such as Pedialyte.

Although vitamin C does not kill the bacteria, it does increase neutrophil and phagocyte activity, aiding the destruction and removal of bacteria and cellular debris; and it bonds with and neutralizes circulating toxins so that they can be excreted. Vitamin C also thins out the mucus, making it easier to cough mucus out of the lungs. In addition, vitamin C takes part in mitochondrial function and strengthens collagen intracellular bonds. Vitamin C can address the symptoms of pertussis in a way that antibiotics cannot.

Soluble Fiber and Type 2 Diabetes

Adding psyllium, a water-soluble fiber, to the normal diet of people with type 2 diabetes improved glycemic response in a 2016 Palestinian study led by Ayman S. Abutair.⁶ The researchers stratified forty non-smokers with type 2 diabetes according to sex, age, body mass index, and fasting blood sugar level and then randomly assigned them to the control group or intervention. The study began with a one-week dietary stabilization phase during which all participants were told to follow a diet plan designed to stabilize serum glucose levels (≤ 30 percent of total energy as fat with 10 percent or less as saturated fat and ≥ 55 percent of energy as carbohydrate, primarily complex carbohydrate). Both groups then continued on their regular diet for eight weeks, but the intervention group also consumed 10.5 grams of psyllium per day (7.0 g before lunch and 3.5 g before dinner) in water.

Unlike the control group, patients consuming psyllium showed significant improvement in glycemic control from baseline. Fasting blood sugar decreased 43.6 mg/dl from baseline in the intervention group (p<0.001) after eight weeks; HbA1c decreased 0.9% (p=0.013); insulin level decreased 8.3 µIU/mL (p<0.001); and C-peptide decreased 2 ng/ml (p<0.001). In addition, people in the intervention group showed significant decreases in weight, BMI, waist circumference, and hip circumference after eight weeks.

The authors say that soluble fiber forms a viscous gel that slows absorption and digestion. “This lowers the sharp rise of blood sugar after meal and improves the sensitivity of the cells to the action of insulin,” they explain. Soluble dietary fiber is found in oats, peas, beans, apples, citrus fruits, carrots, barley, as well as psyllium,

“It seems that soluble fiber from psyllium deserves attention as a potential natural dietary supplement for use in nutritional rehabilitation of type 2 diabetic patients, as it is inexpensive and shows positive results within a short span of time,” conclude the authors.

One caveat: Psyllium supplementation may be problematic for some people with small intestine bacterial overgrowth (SIBO), according to the SIBO Supplement Checklist at  www.siboinfo.com.

Posture, Mood, and Health

“Emotions and thoughts affect our posture and energy levels; conversely, posture and energy affect our emotions and thoughts,” write Erik Peper, PhD, and colleagues.⁷ When we feel threatened, powerless, and defeated, our posture “collapses”; we slump and look downward. Accessing positive memories is more difficult in a slouched position because the mind subconsciously associates negative memories and feelings with that posture. Our thoughts and feelings affect biochemistry and physiology. “Without teaching that a collapsed body posture may affect the healing process, only one half of the mind-body equation that underlies health and illness will be affected,” say Peper and colleagues.

Johannes Michalak and German colleagues performed a recent study on the effect of posture in people with depression.⁸ In earlier studies, people with major depression have shown a “biased memory” for the negative. Recognizing that the motor system can affect emotions, the researchers designed a study to test the effect of posture. They recruited 30 hospitalized patients with major depression disorder and blinded them to the study’s actual purpose by saying that the study was assessing physiological stress reactions to different relaxation positions. Half of the participants were instructed to sit in a slumped posture, and the other half were told to sit in an upright position throughout the 20-minute experiment.

All participants viewed 16 positive words (e.g., beauty and enjoyable) and 16 depression-related words (e.g., exhaustion and dejected) on a computer screen for ten seconds each. Participants were asked to imagine a visual scene in which they experienced the presented word. When this imagination task ended, participants were given a five-minute distraction task during which they mentally rotated letters to determine if the letters were mirror images. Next, the participants were asked to recall all the words they remembered from the imagination task.

The authors report that patients sitting erect had “a more balanced recall of positive and negative words” while those in the slumped position recalled more negative words. The difference was statistically significant. The authors were unable to tell if the erect posture encouraged the recall of more positive words or if people in this group were simply less likely to hold onto the negative words. Larger studies are needed. Body awareness and movement may become useful therapies if posture and gait prove to be active contributors to depression.

Peper and colleagues suggest that people become aware of their posture and adopt an upright stance/position whenever they notice negative thoughts swirling in their minds. Techniques that teach awareness of body positioning and upright position, such as the Alexander technique, the Mensendieck Method, even yoga and tai chi, improve mind as well as body.

Essentials Oils for Sleep Disturbance

Essential oils are among the natural therapies being investigated for mild sleep disturbance. Some plants, including bergamot, lavender, sweet orange, valerian, cedar, and rose, contain chemical compounds that produce a calming or a sleep-inducing effect, according to animal studies. Human studies indicate that essential oils may be helpful for alleviating mild sleep disturbances, but more studies are needed to confirm which botanical oils, dosage, and mode of deliver are most effective, according to two recent review articles.

Angela S. Lillehei, MPH, and Linda L. Halcon, RN, MPH, PhD, conducted a 2014 systematic review, using 15 human studies on the effect of inhaled essential oils (aromatherapy) on sleep that were published in English between 1990 to 2012.⁹ The fifteen studies, 11 of which were randomized controlled trials (RCTs), involved a total of 409 participants. Lavender oil produced statistically significant improvement in sleep quality in four studies. Another six studies reported positive improvement for lavender use or for essential oil mixtures containing lavender oil (not statistically significant, possibly because of cohort size).

Lillehei and Halcon had several criticisms of the studies they found. Importantly, only four of the 15 reported the Latin botanical name, and only one of those four actually analyzed the intervention’s chemical composition. “Different plant species have different chemical constituencies and therefore different therapeutic properties,” say Lillehei and Halcon. “With lavender, for example, Lavandula latifolia is considered stimulating and L. augustifolia is considered relaxing.”⁹ The authors say that future studies also need to investigate mechanisms of action, possible synergistic effects in essential oil mixtures, and assess long-term effects.

Instead of looking at English medical literature, Eunhee Hwang, PhD, and Sujin Shin, PhD, of the Republic of Korea used 13 Korean studies, published between 2000 and August 2013, for their 2015 systematic review of essential oil use to treat sleep disturbance.¹⁰ The studies, four of which were randomized controlled trials, involved 704 participants. Unlike the previous review, botanical oils were administered in different ways: massage (n=7), inhalation (n=5), applied in a poultice (n=1).

Hwang and Shin performed a meta-analysis using 12 of the studies. (The excluded trial lacked appropriate statistical analysis.) Of the many essential oils in these studies, lavender, cypress, and chamomile were the most effective. Hwang and Shin also found that inhalation was more effective than massage and that aromatherapy’s effect was greater in people with an illness compared to healthy participants.

Using a random-effects model, the researchers found an “effect size of 3.72 (95% CI, 0.54-1.75; p<0.001), which indicated that aromatherapy significantly improved sleep.” In comparison with other aromatherapy studies, this effect size was smaller than aromatherapy’s effect on anxiety (6.03), depression (5.11), and stress (5.29) but larger than the effect size on pain (1.97). (The calculated effect size could improve as effective oils and dosages are better identified.)  Interestingly, the effect size of aromatherapy on sleep was less than the effect size of music therapy (4.24), determined in a 2014 Korean meta-analysis of 10 randomized studies, according to Hwang and Shin. Music therapy might be another way to improve sleep.

Hwang and Shin say that more studies are needed to identify essential oils with sedative or hypnotic effects, optimal intervention time, and dosage. They suggest that future studies also measure physiologic indicators, using polysomnography and other methods.

Fish Oil Quality

The International Fish Oil Standards^TM (IFOS) program is a voluntary, globally recognized, third-party fish oil testing and certification program conducted by Nutrasource Diagnostics, Inc. (Guelph, Ontario, Canada).¹¹ Nutrasource Diagnostics, Inc., is a full-service contract research organization offering regulatory consulting, clinical trials, and product testing for the food and dietary supplement industries, including raw materials suppliers. Such testing reassures manufacturers, practitioners, and consumers that the raw materials and finished supplements meet high-quality standards. Fish oil is particularly challenging because of the pollution that may contaminate fish and the fragility of beneficial polyunsaturated fats in the oil. These fats oxidize easily.

The IFOS program does not give blanket assurance that all of a company’s fish oil products meet certification criteria. It tests and certifies specific lots or batches of a company’s oil. Companies that seek lot-specific certified analysis are “top-tiered” companies that are committed to providing high-quality products, according to Scott Fogle, Director of Clinical Information and Laboratory Services at Live Extension®.¹² He says, “A lot of effort is needed in order to provide lot-specific COAs [certificate of analyses] so it also typically means these companies have their own in-house quality control and quality assurance team constantly checking their products and performing quality audits at their manufacturing facilities.” IFOS results are available at the program website, www.ifosprogram.com, and can be accessed by consumers at no cost.

The IFOS program verifies that the tested product meets all testing categories set by the Council for Responsible Nutrition, Global Organization for EPA and DHA Omega-3, and the World Health Organization. The contents of certified five-star fish oil products accurately match label claims, including claims about product ingredient identity and strength. At least 60 percent of the oils in a five-star product must consist of omega-three fats. IFOS also assesses the oils for signs of oxidation. In addition, IFOS tests for contaminants and toxins, including organic pollutants, polychlorinated biphenyls (PCBs), dioxins, and the heavy metals mercury, lead, inorganic arsenic, and cadmium.

In January 2015, IFOS began testing for radiation in response to concerns about contamination from the Fukushima Daiichi nuclear plant since the Japanese earthquake and tsunami in 2011. IFOS uses guidelines from the US FDA, Health Canada, and CODES to assess radiation health concerns. As of December 2016, the IFOS website reports radiation levels are below government guidelines.

To learn more about the IFOS program, visit www.ifosprogram.com.

This column first appeared in Townsend Letter (February/March 2017).

References

1. Lee H, et al.  The Effect of Body Posture on Brain Glymphatic Transport. J Neuroscience. August 5, 2015;25(31):11034-11044.
2. Dreha-Kulaczewski S, et al. Inspiration Is the Major Regulator of Human CSF Flow (abstract). J Neuroscience. February 11, 2015;35(6):2485-2491.
3. Altunaiji SM, Kukuruzovic RH, Curtis NC, Massie J. Antibiotics for whooping cough (pertussis). Cochrane Database Syst Rev. July 18, 2007;(3). PMID 17636756.
4. Humphries S. The Vitamin C Treatment for Whooping Cough. September 7, 2012. [updated protocol at https://drsuzanne.net/wp-content/uploads/2017/10/Vitamin-C-Whooping-Cough-PDF.pdf]
5. Ormerod MJ, UnKauf BM, White FD. A Further Report on the Ascorbic Acid Treatment of Whooping Cough. Canadian Medical Association Journal. September 1937; 268-272.
6. Abutair AS, Naser IA, Hamed AT. Soluble fibers from psyllium improve glycemic response and body weight among diabetes type 2 patients. Nutrition Journal. 2016;15:86.
7. Peper E, Booiman A, Lin I-M, Harvey R. Increase Strength and Mood with Posture. Biofeedback. Summer 2016;44(2);66-72.
8. Michalak J, Mischnat J, Teismann T. Sitting Posture Makes a Difference—Embodiment Effects on Depressive Memory Bias. Clin Psychol Psychother. 2014;21:519-524.
9. Lillehei AS, Halcon LL. A Systematic Review of the Effect of Inhaled Essential Oils on Sleep. J Alternative and Complementary Med. 2014;20(6):441-451.
10. Hwang E, Shin S. The Effects of Aromatherapy on Sleep Improvement: A Systematic Literature Review and Meta-Analysis. J Alternative and Complementary Med. 2015;21(2):61-68.
11. Nutrasource Diagnostics Inc. The International Fish Oil Standards^TM (IFOS^TM) Program launches new website. (Press release) May 28, 2014.
12. Fogle S. Finding a High Quality Fish Oil. Life Extension Magazine. October 2015.

Published December 16, 2023

About the Author

Jule Klotter has a master’s in professional writing from the University of Southern California. She joined Townsend Letter’s staff in 1990. Over the years, she has written abstract articles for “Shorts” and many book reviews that provide information for busy practitioners. She became Townsend Letter’s editor near the end of 2016.