Natural Medicine Journal Immune Health Special Issue 2022

2022 SUPPLEMENT

SPECIAL ISSUE Immune Health

Long-Covid Lessons from Decades of Chronic Fatigue Syndrome Research

Naturalizing the Microbiota in Cesarean-born Babies

Improving Immune-related Outcomes for Gastric Cancer Patients

Multistrain Probiotic and Infectious Disease Symptoms in Elderly Adults

Tina Kaczor, ND, FABNO

Editor In Chief

Lise Alschuler, ND, FABNO Editor, Abstracts & Commentary

Deirdre Shevlin Bell VP of Content and Communications

Karolyn A. Gazella Founder and NMJ Podcast Host

Avery St. Onge Associate Editor

Kristin Bjornsen, MA Copyeditor

Karen Sperry Designer

Katherine Shagoury Group Digital Product Manager

Kelcey George Marketing Manager

Abigael Sleeper Marketing Coordinator

Carmella Perrone Sales Manager, Integrative Practitioner Shannon Gray Digital Sales Representative

Liz Plizga Group Vice President

PUBLISHED BY

Diversified Communications 121 Free St Portland, ME 04101

Natural Medicine Journal (ISSN 2157-6769) is published 13 times per year by Diversified Communications. Copyright © 2022 by Diversified Communications. All rights reserved. No part of this publication may be reproduced in whole or in part without written permission from the publisher. The statements and opinions in the articles in this publication are the responsibility of the authors; Diversified Communications assumes no liability for any information published herein. Advertisements in this publication do not indicate endorsement or approval of the products or services by the editors or authors of this publication. Diversified Communications is not liable for any injury or harm to persons or property resulting from statements made or products or services referred to in the articles or advertisements.

SPECIAL

HEALTH

&

With

Provide

EXPERT INTERVIEW

We Can Learn About Long-Covid from

Syndrome

Contributors

JENNA K. BAILEY, ND, FABNO, received her bachelor’s degree in clinical laboratory science from the University of North Carolina at Chapel Hill and doctorate of naturopathic medicine from Bastyr University. She is also a graduate of the 2-year Seattle Integrative Oncology residency program and is board-certified. Bailey gives talks on naturopathic care and natural health at the Providence Regional Cancer Partnership’s Survivorship Series in Everett, WA, as well as nutrition presenta tions at Providence Integrative Cancer Care in Lacey/Olympia, WA. With her background in laboratory sciences and special interest in hematological cancers, Bailey combines a strong technical under standing of disease with her desire to care for patients. She believes in providing every patient with foundational treatment to make sure they are getting proper sleep, nutrients, vitamins, and hydration, while building a therapeutic relationship to treat the whole person.

LILY HOLMBERG holds a bachelor’s degree in biology and a master’s degree in education. She has worked as a naturalist, a biology educator and has dedicated much of her career to premium, mission-driven and health-focused work starting with Whole Foods Market in the mid-2000s, at various roles over a 10-year period at Gaia Herbs, and most recently at Ōura. Holmberg is a trusted educator on topics including herb alism and herbal supplements, medicinal mushrooms, and hemp and has presented on these topics for national audiences. Holm berg has been a runner for more than 20 years and is passionate about gardening, cooking, mindfulness, and advocating for people to spend more time in nature.

TORI HUDSON, ND, graduated from the National University of Naturopathic Medicine (NUNM) in 1984 and has served the college in several capac ities. She is currently a clinical professor at NUNM, Southwest College of Naturopathic Medicine, and Bastyr University. Hudson is the medical director of A Woman’s Time in Portland, OR, and director of product research and education for VITANICA. She is the founder and codirector of Naturopathic Education and Research Consortium (NERC), a nonprofit organization for accredited naturopathic resi dencies. Hudson is a faculty member of the Fellowship in Integra tive Health & Medicine, Academy of Integrative Health & Medicine.

TINA KACZOR, ND, FABNO, is editor-in-chief of Natural Medicine Journal and the creator of Round Table Cancer Care. Kaczor is a naturopathic physician board certi fied in naturopathic oncology. She received her naturopathic doctorate from the National University of Natural Medicine and completed her residency at Cancer Treatment Centers of America. She is also the editor of the Textbook of Naturo pathic Oncology and cofounder of The Cancer Pod, a podcast for cancer patients, survivors, caregivers, and everyone in between.

ANNE KENNARD, DO, is tripleboard certified in obstetrics and gyne cology, integrative medicine, and lifestyle medicine and holds a bach elor’s degree in nutrition science. She completed a 2-year fellowship in integrative medicine through the Andrew Weil Center for Integrative Medicine and has additional training in contemplative medicine, herbal medicine, and Ayurveda. She is also a registered yoga instructor. Kennard serves as the associate program director for OB/GYN and director for Integrative and Life style Medicine at Marian Regional Medical Center in Santa Maria, CA.

BRETT WILLIAMS, MD, is an asso ciate professor in the Department of Internal Medicine, Division of Infec tious Diseases, at Rush Medical College in Chicago, IL. He also chairs both the Biohazard Committee and the Dual Use Research of Concern Committee. Williams earned his medical degree from University of Toledo College of Medicine before completing his internal medicine residency at Beth Israel Deaconess Medical Center in Boston and his infectious disease fellowship at Rush University Medical Center. Williams’s research focuses on the role gut microbiota play in the chronic immune activation seen in HIV infected individuals.

BREAK

The groundbreaking, safe, and fast-acting way to help your patients find their calm.

Available At: emersonecologics.com | fullscript.com | meyerdc.com

Available At: emersonecologics.com | fullscript.com | meyerdc.com

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

*These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure, or prevent any disease.

Lactobacillus Crispatus and Bacterial Vaginosis

REFERENCE

Armstrong E, Hemmerling A, Steve Miller, et al. Sustained effect of LACTIN-V (Lacto bacillus crispatus CTV-05) on genital immunology following standard bacte rial vaginosis treatment: results from a randomised, placebo-controlled trial. Lancet Microbe. 2022;3(6):e435-e442.

STUDY OBJECTIVE

To investigate the effect of a live biother apeutic vaginal agent containing L crispatus CTV-05 (LACTIN-V) on genital immunology and key vaginal bacteria

KEY TAKEAWAY

This study suggests that the vaginal application of LACTIN-V is associated with sustained reductions in mucosal inflammation and possibly improved mucosal barrier function.

DESIGN

A substudy of a randomized, placebo-controlled, phase 2b trial of LACTIN-V to reduce bacterial vaginosis recurrence

PARTICIPANTS

The original study recruited 228 women (aged 18–45 years) to partake in a phase 2b trial of LACTIN-V to reduce bacterial vaginosis recurrence. The study subset reviewed here included 66 highly adherent women who were randomly selected from the original study (32 in the LACTIN-V group; 34 in the placebo group). The median age was 33 years. None of the women tested positive for human immunodeficiency virus (HIV), syphilis, Neisseria gonorrhoeae, Chla mydia trachomatis, or Trichomonas vaginalis at baseline. Women were negative for pregnancy and urinary tract infection. Baseline participant charac teristics and sexual behaviors, including recent sex and hormonal-contraceptive use and ethnicity, did not substantially

differ between groups. Women who met at least 3 of 4 clinical Amsel criteria for bacterial vaginosis and had a Nugent score of 4 to 10 from Gram staining were eligible.

INTERVENTION

All participants received a 5-day course of vaginal metronidazole 0.75% gel. After this treatment, they were randomly assigned to receive either LACTIN-V or placebo, applied vaginally once per day for 5 days for the first week and then twice per week for 10 more weeks. Follow-up visits occurred 4, 8, 12, and 24 weeks after enrollment.

Lactobacillus crispatus CTV-05 (LACTIN-V) is a live biotherapeutic product that contains a naturally occur ring strain of L crispatus. LACTIN-V is composed of a powder containing 2 x 10 9 colony-forming units of L cris patus CTV-05 preserved with inactive ingredients and administered by a pre filled applicator.

STUDY PARAMETERS ASSESSED

Investigators assayed soluble immune factors and the absolute abundance of bacterial taxa using multiplex ELISA and quantitative polymerase chain reaction (PCR).

PRIMARY OUTCOME

The primary outcomes were the vaginal interleukin 1 alpha (IL-1a) and soluble E-cadherin concentrations at 24 weeks (ie, 13 weeks after treatment cessation, whether LACTIN-V or placebo).

Other outcomes included vaginal concentrations of soluble immune factors and the absolute abundance of key vaginal bacteria including L cris patus, L crispatus strain CTV-05, L iners, L jensenii, L gasseri, Gardnerella vaginalis, Atopobium vaginae, Megas phaera species, and Prevotella species.

KEY FINDINGS

By Tori Hudson, ND

LACTIN-V treatment was associated with significantly lower concentra tions of the proinflammatory cytokine IL-1a ( P =0.042), a marker of inflam mation, and soluble E-cadherin ( P =0.035), a biomarker of epithelial barrier disruption.

In addition, among the 6 exploratory endpoints, LACTIN-V was associated with elevated concentrations of induced protein 10 (IP-10) at 23 weeks. Inter feron (IFN) alpha 2a and IL-17A were undetectable in more than 50% of the samples. Detectability of IFN-alpha 2a or IL-17A was not significantly associ ated with treatment.

TRANSPARENCY

This study was funded by the Cana dian Institutes of Health and Research and the National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID). One of the authors of this study, CR Cohen, MD, is chair of the scientific advisory board for Osel, the biotherapeutics company whose product pipeline includes LACTIN-V. He reports grants from NIAID and the NIH National Institute of Child Health and Human Development. He holds stock options in Osel and Evvy. Another author, B Coburn, PhD, reports grants from the Western Foundation, Canadian Insti tutes of Health Research, Canadian Cancer Society, McLaughlin Foun dation, National Cancer Institute, and Cystic Fibrosis Foundation and receipts for research from Nubiyota, a microbiome therapeutics company focused on the development of novel microbiota-based drugs to restore gut equilibrium. Coauthor R Kaul reports a grant from Canadian Institutes of Health Research.

Possibilities in reducing the risk of recurrence

PRACTICE IMPLICATIONS AND LIMITATIONS

Bacterial vaginosis (BV) affects 15% to 50% of reproductive-aged women worldwide.1 The recurrence rate is quite problematic, and even after treatment with an indi cated antibiotic agent, 20% to 75% of women have a recur rence within 3 months.2 BV is associated with increased risk of sexually transmitted infections (STIs) including HIV, as well as premature birth.3 BV also leads to negative emotional, sexual, and social effects and is an economic burden for patients. If we could reduce the risk of recurrence, let alone promote primary prevention, we would be helping provide a much-needed solution in women’s health.

I’ll get to the study implications and limitations of the current study in a moment, but first, let’s look at the orig inal study that spawned the current substudy. I see that study as having greater practice implications. The original study (Cohen et al, NEJM, 2020) involved a phase 2b trial to assess whether treatment with LACTIN-V after vaginal metronidazole for BV lowered the incidence of recurrence of BV. Women aged 18 to 45 years with BV completed a 5-day course of vaginal metronidazole gel (0.75%). Within 48 hours of completing that treatment, they were random ized to vaginal LACTIN-V for 11 weeks vs placebo. This intervention required participants to insert an applicator nightly for 5 days, then twice weekly for 10 weeks. The primary outcome was the percentage of women who had a recurrence of BV by week 12. Investigators randomized 228 women, with 152 in the treatment group and 76 in the placebo group. By week 12, BV recurrence was significantly lower in the LACTIN-V group, with a 30% rate of recur rence in the LACTIN-V group (compared to a 45% rate of recurrence in the placebo group) and with a sustained effect in the treatment group at week 24.

Now, to our current substudy, which resulted in a sustained reduction in genital inflammation and a biomarker of epithe lial integrity. LACTIN-V was associated with the concentrations of soluble immune factors and an abundance of multiple bacterial taxa, which bodes well for genital immu nity. These sustained genital immune effects were primarily mediated by a reduced amount of bacterial vaginosis–associ ated taxa, especially Prevotella spp and Megasphaera spp, and to a lesser extent, an elevated amount of L crispatus. There

are strong links between vaginal microbiota and HIV risk, suggesting that promoting a predominance of L crispatus in the vagina might reduce the risk of HIV.

Women with L crispatus predominance in their vaginal ecosystems also exhibit fewer transitions to bacterial vaginosis–type microbiota than women with other Lactobacillus species dominating, such as L iners predominance. This suggests that L crispatus can competitively inhibit or exclude inflammatory bacterial vaginosis–associated bacteria. This is, in part, mediated by the production of lactic acid and anti microbial metabolites. We have other evidence that shows that L crispatus is a key producer of lactic acid in the vagina.4

There are some limitations of the study. Investigators assessed STIs only at initial screening, and they only tested for them again if women were symptomatic. The stage of the menstrual cycle was not recorded unless the women were menstruating. A fluctuation in the normal sex hormones is a potential determinant of genital immunology and pH. The testing used was targeted qPCR rather than 16SrRNA gene sequencing, which limited the ability to evaluate the vaginal microbiota and identify contributions by other microbes. The study involved only US American women, though it was an ethnically heterogeneous cohort.

CONFLICT OF INTEREST DISCLOSURE

Dr Tori Hudson is the co-owner of a women’s supplement company, Vitanica, which offers a broad range of women’s health, nutritional, and herbal products including oral and vaginal-use probiotic species and strains for prevention and treatment of urogynecological conditions. She is also a medical advisor to Nutritional Fundamentals for Health, Symphony, Integrative Therapeutics, and Gaia Herbs Pro.

REFERENCES

1 Koumans EH, Sternberg M, Bruce C, et al. The prevalence of bacterial vaginosis in the United States, 2001–2004; associations with symptoms, sexual behaviors, and reproductive health. Sex Transm Dis. 2007;34(11):864-869.

2 Vodstrcil LA, Muzny CA, Plummer EL, Sobel JD, Bradshaw CS. Bacterial vaginosis: drivers of recurrence and challenges and opportunities in partner treatment. BMC Med. 2021;19(1)194.

3 Nelson DB, Hanlon A, Hassan S, et al. Preterm labor and bacterial vaginosisassociated bacteria among urban women. J Perinat Med. 2009;37(2):130-134.

4 Abdelmaksoud AA, Koparde VN, Sheth NU, et al. Comparison of Lactobacillus crispatus isolates from Lactobacillus-dominated vaginal microbiomes with isolates from microbiomes containing bacterial vaginosis-associated bacteria. Microbi ology (Reading). 2016;162(3):466-475.

Vaginal Seeding After Cesarean Delivery

REFERENCE

Song SJ, Wang J, Martino C, et al. Naturalization of the micro biota developmental trajectory of Cesarean-born neonates after vaginal seeding. Med (N Y). 2021;2(8):951-964.e5.

STUDY OBJECTIVE

To provide an adequately powered longitudinal study to determine the effect on neonatal microbiota of restoring exposure to maternal vaginal fluids after cesarean (CS) birth

KEY TAKEAWAY

Vaginal seeding of cesarean–born babies naturalizes their microbiota and can engraft multiple body sites.

DESIGN

Multicentered observational study

PARTICIPANTS

The study followed 177 babies from birth to 1 year (98 born vaginally, 79 born via cesarean delivery). Thirty of the cesarean babies were swabbed with a maternal vaginal gauze at time of birth. All seeded cesarean babies were negative for Group B Streptococcus and for sexually trans mitted infections (STI) and had intact membranes at time of birth. Demographic details were as follows:

• 101 babies were born in the United States, 20 in Spain, 50 in Chile, and 6 in Bolivia

• 52% of babies were female, 48% male

• 75% of vaginally born babies were breastfeeding dominant; 69% of cesarean-delivered babies and 53% of seeded-cesarean-delivered babies were breast feeding dominant.

INTERVENTION

Vaginal seeding via vaginal maternal gauze of cesarean-born infants

STUDY PARAMETERS ASSESSED

Investigators obtained stool, mouth, and skin samples to analyze microbiota diversity at different body sites through use of compositional tensor factorization, which allows for analyzing diversity over time.

PRIMARY OUTCOME

Microbial trajectory in multiple body sites of seededcesarean babies compared to vaginally delivered babies vs cesarean births (not seeded)

KEY FINDINGS

By Anne Kennard, DO, FACOG, ABOIM, Dipl-ABLM

The trajectory of gut microbiota development in CS-born infants diverged from that of vaginally born infants through the entire 1st year of life. Seeded CS-born infants led to a develop mental microbiota trajectory that more closely resembled that of vaginally born infants, most prominently in feces and skin.

The effectiveness of seeding was variable depending on the bacterial taxa; for example, investigators identified that gut bacteria, including Bacteroides, Streptococcus, and Clostridium, were enriched in seeded CS infants, and these infants had microbes missing in CS-born babies. Other taxa did not prove to have an effective seeding and did not persist in the infant microbiome. The seeding differences were most prominent in the infant feces.

During the taxonomic analysis, investigators observed a notable overlap between the species present in the maternal vagina and those present in sites including feces, skin, nose, and mouth of the baby, as compared with nonpregnant controls. This indicates that the perinatal vaginal microbiome is pluripotent and can engraft multiple body sites in the neonate.

Of note, all 3 groups demonstrated maximum divergence of microbiota at time of birth and then converged over time to 1 year, with seeded CS babies more closely approximating, but not equaling, vaginally born babies.

TRANSPARENCY

Funding for this study was provided by C&D, Emch Fund, CIFAR, Chilean CONICYT and SOCHIPE, Norwegian Institute of Public Health, Emerald Foundation, NIH, National Institute of Justice, and Janssen.

A promising method for increasing naturalization of neonatal microbiota

This study adds to the growing body of evidence that vaginal seeding partially restores infant microbiota of cesarean-born infants to approximate that of vaginally born infants.

PRACTICE IMPLICATIONS & LIMITATIONS

Over the past decade, research has demonstrated the multitude of ways that the microbiome can impact human health and the effects that mode of delivery can have on the microbiome. Differences in microbiome diversity and dysbiosis have been linked with childhood infections, cognitive and behavioral disorders, immune diseases, and potentially lifelong effects on obesity and metabolic distur bances.1-4 These differences may be due to many factors affecting the newborn’s microbiome, one of which is the mode of delivery.

Several studies have noted a difference in the microbiota and clinical disease burden in cesarean-born versus vaginally born children, although this idea is not without its detrac tors.5,6 Regardless, the practice of “vaginal seeding” has been developed, whereby gauze is soaked in maternal vaginal fluid and then wiped over the neonate’s eyes, mouth, and skin to inoculate the infant.

Up to this point, there has not been an adequately powered longitudinal study to demonstrate differences in the micro biota at different colonization sites. This study adds to the growing body of evidence that vaginal seeding partially restores infant microbiota of cesarean-born infants to approximate that of vaginally born infants.

While promising for potentially long-term health impli cations, the findings from this study may also influence future clinical practice recommendations. Presently, the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists (ACOG) both have formal statements that recommend against the practice of vaginal seeding. The American College of Obstetricians and Gynecologists Committee Opinion number 725 acknowl edges that “the increase in the frequency of asthma, atopic disease, and immune disorders mirrors the increase in the rate of cesarean delivery, the theory of vaginal seeding is to allow for proper colonization of the fetal gut and, therefore, reduce the subsequent risk of asthma, atopic disease, and immune disorders.” However, it recommends against the practice outside of the context of an institutional review board–approved research protocol.7 The college does give

guidance that if vaginal seeding is planned/performed, the patient should be tested and negative for diseases that can affect the newborn, including serum testing for herpes simplex virus and cultures for group B streptococci, Chlamydia trachomatis, and Neisseria gonorrhoeae. 7

The American Academy of Pediatrics (AAP) similarly states that “vaginal seeding is not recommended outside of a research study because of current lack of evidence of benefit and risk of infectious exposure” and should be strongly cautioned against in the setting of group B strep tococci and herpes simplex virus, including education about the possibility of false negative testing for group B streptococci.8 The academy also notes that there is a signif icant influence of breastfeeding and maternal areola on the microbiome regardless of mode of delivery,9 and it questions the long-term consequences of cesarean delivery on human microbiota given that the available body of literature does not generally extend past age 2 years.8 The 2 position state ments do not specifically address the body of literature that suggests mode of delivery has long-term effects on childhood and adult obesity and a related role between mode of delivery and microbiome.10-13

While vaginal seeding potentially could be a clinical tool to mitigate the rise of obesity, immune disorders, and neuro developmental disorders in the United States, it is unlikely that most obstetricians and pediatricians in the United

LISTEN TO NATURAL MEDICINE JOURNAL ON THE GO.

PODCAST SERIES

SUBSCRIBE TO OUR PODCAST

States will be able to recommend and/or perform this practice with such oppositional position statements from profes sional organizations as cited above. In the current climate, recommending and/or performing vaginal seeding exposes the clinician to any potential liability that may occur and is unlikely to be recommended in a clinical setting outside of a research protocol.

The 2 position statements were published in 2017 and 2022, respectively, and may be updated in the future to reflect the translational research that this article and others have provided. However, for several more years, a tension may exist between clinicians’ awareness of the potential positive implications of this practice vs the potential liability. This tension may be mitigated in other settings,

such as homebirth or a freestanding birth center with a certified nurse or licensed midwife, as well as ongoing pediatric care in a naturopathic setting as opposed to with a medical or osteopathic physician. An educated patient may also perform this practice independently, without the express knowledge or consent of the care team, though transparency is ideal so that health practitioners can properly test for infectious organisms and fully evaluate the infant if any concerns arise regarding potential neonatal infection.

One hopes that research protocols will continue to expand longitudinal data, including larger sample sizes and longer-term outcomes, with significant clinical differences and minimal harm noted. Accumulating ongoing clinical data will be key to changing the AAP and ACOG position statements so that

the practice of vaginal seeding may be used widely in clinical practice in the United States in a safe and effective way.

REFERENCES

1 Stokholm J, Blaser MJ, Thorsen J, et al. Maturation of the gut microbiome and risk of asthma in childhood. Nat Commun. 2018;9:141.

2 Andersen V, Möller S, Jensen PB, Møller FT, Green A. Caesarean delivery and risk of chronic inflammatory diseases (inflammatory bowel disease, rheumatoid arthritis, coeliac disease, and diabetes mellitus): a population based registry study of 2,699,479 births in Denmark during 1973-2016. Clin Epidemiol. 2020;12:287-293.

3 Blustein J, Attina T, Liu M, et al. Association of caesarean delivery with child adiposity from age 6 weeks to 15 years. Int J Obes. 2013;37:900-906.

4 Cox LM, Yamanishi S, Sohn J, et al. Altering the intestinal microbiota during a critical developmental window has lasting metabolic consequences. Cell. 2014;158:705-721.

5 Chu D, Ma J, Prince A, et al. Maturation of the infant microbiome community structure and function across multiple body sites and in relation to mode of delivery. Nat Med 2017;23:314-326.

6 Stinson LF, Payne MS, Keelan JA. A critical review of the bacterial baptism hypothesis and the impact of cesarean delivery on the infant microbiome. Front Med. 2018;5:135.

7 American College of Obstetricians and Gynecologists. Vaginal seeding. Committee Opinion Number 725. https://www.acog.org/clinical/clinical-guid ance/committee-opinion/articles/2017/11/vaginal-seeding. Accessed September 10, 2022.

8 Nolt D, O’Leary ST, Aucott SW. Risks of infectious diseases in newborns exposed to alternative perinatal practices. Pediatrics. 2022;149(2).

9 Pannaraj PS, Li F, Cerini C, et al. Association between breast milk bacterial communities and establishment and development of the infant gut microbiome. JAMA Pediatrics. 2017;171(7):647.

10 Tun HM, Bridgman SL, Chari R, et al. Roles of birth mode and infant gut micro biota in intergenerational transmission of overweight and obesity from mother to offspring. JAMA Pediatr. 2018;172:368-377.

11 Masukume G, O’Neill SM, Baker PN, et al. The impact of caesarean section on the risk of childhood overweight and obesity: new evidence from a contemporary cohort study. Sci Rep. 2018;8:15113.

12 Kuhle S, Tong OS, Woolcott CG. Association between caesarean section and childhood obesity: a systematic review and meta-analysis. Obes Rev. 2015;16:295-303.

13 Mueller NT, Mao G, Bennet WL, et al. Does vaginal delivery mitigate or strengthen the intergenerational association of overweight and obesity? Findings from the Boston Birth Cohort. Int J Obes (Lond). 2017;41:497-501.

Improved Gastrectomy Outcomes With Omega-3s

A controlled trial involving gastric cancer patients

REFERENCE

Yang J, Zhang X, Li K, et al. Effects of EN combined with PN enriched with n-3 polyunsaturated fatty acids on immune related indicators and early rehabilitation of patients with gastric cancer: a randomized controlled trial. Clin Nutr. 2022;41(6):1163-1170.

STUDY OBJECTIVE

To evaluate the effect of adding omega-3 polyunsaturated fatty acids (PUFA) to usual postsurgical nutritional care in individuals undergoing gastrectomy for gastric cancer

KEY TAKEAWAY

The addition of n-3 polyunsaturated fats to parenteral nutrition in combination with enteral nutrition following gastrectomy improves immune parameters, inflammatory markers, and nutritional parameters and reduces postop erative complications.

DESIGN

Prospective, randomized, controlled trial with patients undergoing elective radical gastrectomy at the West China Hospital of Sichuan University

PARTICIPANTS

Investigators recruited 123 patients with biopsy-confirmed gastric adenocarcinoma, aged 18 to 80 years with a mean age of 57.8 ± 10.5 years. A total of 120 patients completed the study: 60 in the control group and 60 in the study group (male=82; female=38).

There were no significant differences between the study and control groups in regard to gender; age; weight; body mass index (BMI); tumor location; tumor, node, metastasis (TNM) stage; or surgical parameters. There were also no significant differences in baseline parameters (immune function, inflammatory markers, and nutrition markers).

INTERVENTION

The intervention period consisted of the 5 days immedi ately postoperative. Both the study group and the control group received the same base of enteral nutrition (EN) plus parenteral nutrition (PN). The study group received n-3 polyunsaturated fatty acids in their PN.

EN was 500 mL of 5% glucose and sodium chloride through a nasojejunal tube starting day 1. Day 2 EN was an enteral

nutrition emulsion (Huarui). Researchers calculated energy requirements based on ideal weight x 30 kcal/kg/d. PN was given via peripheral or central venous routes starting day 1 postop. Both groups received Kaviven™ PI (Huarui). The study group additionally received 0.2 g/kg/d of 10% fish oil fat emulsion (Omegaven®, Huarui), which contained 1.25 to 2.82 g eicosapentaenoic acid (EPA) and 1.44 to 3.09 g docosahexaenoic acid (DHA; 10 g/100 mL).

STUDY PARAMETERS ASSESSED

Investigators assessed the following through fasting blood collected the day before surgery and again on postopera tive days 1, 3, and 5:

• Immune parameters: lymphocyte count (LYM), cluster of differentiation 3+ (CD3+), CD4+, CD8+, and CD4+/ CD8+

• Inflammatory indicators: white blood cells (WBC), C-reactive protein (CRP), interleukin 6 (Il-6), tumor necrosis factor alpha (TNF-α)

• Nutrition parameters: hemoglobin (Hb), total protein (TP), albumin (Alb), prealbumin (PAB), and transferrin (TAF)

• Incidence of postoperative complication

Secondary endpoints included:

• Time to first aerofluxus (flatus) and defecation

• Postoperative length of stay

• Rate of unplanned 30-day readmission

• Unplanned reoperation after surgery

By Jenna Bailey, ND, FABNO Specifically for gastric cancer, we have seen complication rates decrease from around 28% to 10% with these fast-track procedures.

PRIMARY OUTCOME

To assess the effect of n-3 PUFA–enriched PN on immune- and inflammatory-related indices com pared to PUFA PN without n-3.

KEY FINDINGS

Findings revealed statistically significant differences in several immune parameters (LYM, CD3+, CD4+, and CD4+/CD8+; no difference in CD8+ between groups), as well as improvement in inflammatory indicators (CRP, IL-6, and TNF-α; CRP in study group lower than in control group at days 3 and 5 postop; TNF-α in study group lower than in control group at day 5 postop), and nutri tion parameters (total protein P level in study group higher than in control group at day 5 postop; Alb and PAB in study group higher than in control group at days 3 and 5 postop).

Additionally, there were fewer postoperative complications in the study group (4 cases) compared to usual care (12 cases; P=0.032).

For secondary outcomes, there was a statistically significant decrease in time to flatus and defecation for the study group (P=0.044 and P=0.002, respec tively).

Researchers saw no differences in postoperative length of stay or the rate of unplanned 30-day readmission or reoperation between the 2 groups.

TRANSPARENCY

No conflicts of interest.

PRACTICE IMPLICATIONS & LIMITATIONS

In 2020, gastric cancer was the 5th most common cancer and the 4th leading cause of death worldwide (accountable for about 7.7% cancer deaths1), which amounts to about 1.1 million new cases and 770,000 deaths attributable to the disease. It is predicted that by 2040 there will be about 1.8 million new cases and 1.3 million deaths. Unfortunately, survival rates remain low as the disease is often found in an advanced stage. We are now also seeing, similarly to other tumor types, a rise in cases among younger individuals (aged less than 50 years). There are many modifiable risk factors including smoking, alcohol consumption, intake of salt-preserved foods, obesity, and reflux.2

Although there have been advances in treatment, surgery remains the only treatment offered with curative intent. However, 5-year survival for stage I resected gastric cancer is only 70%, and for stage IIB and beyond, 5-year survival is less than 30%.3

Risk for postoperative complications following total gastrectomy has been found to be as high as 36% and mortality rate as high as 4.7% in the 30 days following surgery.4

So how can we reduce these complications and improve morbidity and mortality rates for these individuals, especially given that surgery and anesthesia can also cause immunosuppression and increased inflammation?5

Researchers have found several relatively simple and clinically applicable tools that can help predict complications in individuals undergoing gastrectomy.

Prior to surgery, a low prognostic nutritional index (PNI) is associated with a lower 5-year overall survival. The PNI is equal to 10 x serum albumin value (g/dL) + 0.005 x total lymphocyte count in the peripheral blood (per mm3 ). PNI values less than 46 were associated with a 21.1% 5-year overall survival, and PNI values greater than 46 were associated with a 54.15% 5-year overall survival.6 Screening individuals before surgery may allow for improving their PNI and subsequently their postoperative course and overall survival, especially given the high (66.7%–80.4%) incidence of malnutrition in individuals with gastric cancer and the almost 2-fold increased risk for postoperative complications associated with malnutrition.7

C-reactive protein (CRP) has also been found to be an independent risk factor for predicting complications following total gastrectomy. A retrospective study found that CRP was elevated on day 3 postop in 60.4% of the patients who developed complications.8

Surgical practices are changing, and we are seeing more fast-track procedures that allow for higher carbohydrate and protein intake in the preoperative period, in addition to higher oral intake in the postoperative period and implementation

of parenteral nutrition when oral intake is not adequate. Specifically for gastric cancer, we have seen complication rates decrease from around 28% to 10% with these fast-track procedures. Additional factors that play a role are optimal pain control, improving gut function, and protecting gut mucosal barrier.9 Adequate intake of n-3 PUFAs can modify all those factors. The authors of the current study under review write:

“n-3 PUFAs in gastrointestinal cancer cannot only reduce inflammatory reactions, and improve the postop erative curative effect, but also improve immune suppres sion. The possible mechanism has been discussed, EPA and DHA could regulate the immune inflammatory response by enhancing T cell function, and B cell func tion, altering membrane fluidity, lipid peroxide formation, and eicosanoid production; regulating of gene expression and subsequently inhibiting many aspects of inflammation, including leukocyte chemotaxis, adhesion molecule expression and leukocyte-endothelial adhesive interactions, production of eicosanoids like prostaglan dins and leukotrienes from the n-6 fatty acid arachidonic acid and production of proinflammatory cytokines.”

Yang et al investigated the use of n-3 PUFA–enriched paren teral nutrition in combination with enteral nutrition on days 1 to 5 following gastrectomy in individuals with gastric adenocarcinoma. Individuals in the study arm were given 0.2 g/kg/d of 10% fat oil emulsion containing 1.25 to 2.82 g EPA and 1.44 to 3.09 g DHA (10 g/100 mL).10 If we were to translate this into an oral dose for a 150-pound individual, this would be anywhere from 1.7 to 3.8 g EPA and 1.95 to 4.2 g DHA. Fortunately, achieving these doses would be attainable with commercially available omega-3 fatty acids with high concentrations of EPA and DHA. Enteral supple mentation and parenteral supplementation have been shown to increase EPA in plasma cell membranes, though incorpo ration was slower with enteral supplementation.11

The individuals who received n-3 PUFA–enriched paren teral nutrition had improved immune parameters, inflam matory indicators, and nutritional markers. Additionally, they had fewer postoperative complications. There was

also a decrease in time to first flatus and defecation but no difference in postoperative length of stay. Unfortunately, parenteral nutrition is often underused in the postoperative setting, especially in individuals who receive enteral nutrition but remain undernourished.12

Although we rarely have the opportunity to influence the postoperative course while an individual is inpatient, it would seem that in the case of gastrectomy, recommending postoperative oral n-3 PUFAs would be not only safe but beneficial for these individuals. Using tools such as the PNI and CRP may be useful predictive markers for those who may benefit the most from supplementation. Additionally, given that about 60% of patients will undergo surgery to treat their cancer, healthcare providers should consider n-3 PUFAs across tumor types in the postoperative setting.

REFERENCES

1 Mocan L. Surgical management of gastric cancer: a systematic review. J Clin Med 2021;10(12):2557.

2 Yang J, Zhang X, Li K, et al. Effects of EN combined with PN enriched with n-3 polyunsaturated fatty acids on immune related indicators and early rehabili tation of patients with gastric cancer: a randomized controlled trial. Clin Nutr 2022;41(6):1163-1170.

3 Mocan L. Surgical management of gastric cancer: a systematic review. J Clin Med 2021;10(12):2557.

4 Bartlett E, Roses R, Kelz R, Drebin J, Fraker D, Karakousis G. Morbidity and mortality after total gastrectomy for gastric malignancy using the American College of Surgeons National Surgical Quality Improvement Program Database. Surgery 2014;156(2):298-304.

5 Kim R. Effects of surgery and anesthetic choice on immunosuppression and cancer recurrence. J Transl Med. 2018;16(1):8.

6 Jiang N, Deng JY, Ding XW, et al. Prognostic nutritional index predicts postoper ative complications and long-term outcomes of gastric cancer. World J Gastroen terol. 2014;20(30):10537-10544.

7 Yang J, Zhang X, Li K, et al. Effects of EN combined with PN enriched with n-3 polyunsaturated fatty acids on immune related indicators and early rehabili tation of patients with gastric cancer: a randomized controlled trial. Clin Nutr 2022;41(6):1163-1170.

8 Okubo K, Arigami T, Matsushita D, et al. Clinical impact of creatine phosphokinase and c-reactive protein as predictors of postgastrectomy complications in patients with gastric cancer. BMC Cancer. 2021;21(1):95.

9 Feng F, Ji G, Li JP, et al. Fast-track surgery could improve postoperative recovery in radical total gastrectomy patients. World J Gastroenterol. 2013;19(23):36423648.

10 Yang J, Zhang X, Li K, et al. Effects of EN combined with PN enriched with n-3 polyunsaturated fatty acids on immune related indicators and early rehabili tation of patients with gastric cancer: a randomized controlled trial. Clin Nutr 2022;41(6):1163-1170.

11 van der Meij BS, van Bokhorst-de van der Schueren MA, Langius JA, Brouwer IA, van Leeuwen PA. n–3 PUFAs in cancer, surgery, and critical care: a systematic review on clinical effects, incorporation, and washout of oral or enteral compared with parenteral supplementation. Am J Clin Nutr. 2011;94(5):1248-1265.

12 Yang J, Zhang X, Li K, et al. Effects of EN combined with PN enriched with n-3 polyunsaturated fatty acids on immune related indicators and early rehabili tation of patients with gastric cancer: a randomized controlled trial. Clin Nutr 2022;41(6):1163-1170.

A Multistrain Probiotic May Provide Immune Support in the Elderly

Results from a double-blind, placebo-controlled study

REFERENCE

Sandionigi A, De Giani A, Tursi F, et al. Effectiveness of multistrain probiotic formulation on common infectious disease symptoms and gut microbiota modulation in flu-vaccinated healthy elderly subjects. Abbassi MS, ed. Biomed Res Int. 2022;2022:3860896.

STUDY OBJECTIVE

To see whether the probiotic formulation reduced “common infection symptoms” in study participants

KEY TAKEAWAY

Common symptoms of infection in the elderly were less prevalent in those who took a multistrain probiotic

DESIGN

Randomized, double-blind, placebo-controlled, parallelgroup study

PARTICIPANTS

Fifty healthy elderly subjects, aged between 60 to 80 years and vaccinated for influenza, were assigned randomly to probiotics (n=25, with 17 female) or placebo (n=25, with 19 female) groups.

INTERVENTION

The study period was 56 days, with 28 days of intervention or placebo (3 time points were T0, T28, T56). Participants in the intervention group consumed 1 unit of a probiotic formulation, and the other group consumed a placebo that contained only the excipients used in the intervention product.

Both groups mixed their study material in nonsparkling water and consumed it away from meals.

The probiotic formulation contained probiotic strains derived from samples of human origin: 1×109 colonyforming units (CFU) of Lactiplantibacillus plantarum subsp plantarum (formerly Lactobacillus plantarum)

PBS067, 1×109 CFU of Bifidobacterium animalis subsp lactis BL050, 1×109 CFU of Bifidobacterium longum subsp infantis BI221, 1×109 CFU of Bifidobacterium longum subsp longum BLG240, and common excipients used in food supplements. The placebo contained only common excipients. Product was supplied by Roelmi HPC (Origgio, Italy).

STUDY PARAMETERS ASSESSED

By Lily Holmberg and Brett Williams, MD

• Common Infectious Disease (CID) symptom occurrence. The CID symptoms were described as:

Respiratory symptoms (RI; ie, cold, cough, sneezing, sore/itchy throat, nasal obstruction, with or without fever)

Gastrointestinal symptoms (GI; ie, vomiting, diarrhea, abdominal pain)

Musculoskeletal symptoms (MS; ie, tension head aches, pain, weakness, stiffness, joint noises, decreased range of motion)

• Researchers computed 1 day with concomitant CID symptoms as 1. They calculated the number of days and the number of subjects with at least 1 CID.

• Number of days with CID symptoms

• Salivary immunoglobulin A (IgA) concentration

• Salivary total antioxidant capacity

• Fecal β-defensin2 (HBD-2)

• Fecal calprotectin

• Gut microbiota diversity

PRIMARY OUTCOME

• Common symptom occurrence

• Number of days with common symptoms

• Salivary IgA concentration

• Salivary total antioxidant capacity

• Fecal β-defensin2 (HBD-2)

• Fecal calprotectin

• Gut microbiota diversity

KEY FINDINGS

Elderly participants who received multistrain probiotic supple mentation were less likely to experience CID symptoms than those in the placebo group (P<0.05). Participants in the probi otic group experienced symptoms on fewer days during the study than subjects in the placebo group (P<0.01).

TRANSPARENCY

This study was financed by Lombardy Region POR FESR 2014-2020 in support of the development of advancements.

PRACTICE IMPLICATIONS & LIMITATIONS

Research interest in human aging, including caring for older generations with waning immune health, continues to be an important area of clinical research, especially in the wake of the pandemic. The urgency surrounding how we can better protect our most vulnerable populations, including our elderly, is of interest worldwide. Research focusing on immu nosenescence, or the way the aging immune system changes throughout the lifespan, has become a growing field in search of ways to support the aging process and potentially improve one’s later years.

An aspect of this research necessarily involves looking at the role the gut microbiome plays in the human immune response. It is well-known that the gut microbiota plays important roles in the response to disease,1 and that role may be impacted in advanced years,2 but what is less understood in the elderly population is how lifestyle factors such as diet,3 exercise,4 and other interventions, including the use of probi otic supplements,5 may support or augment the immune response.

To safeguard the elderly from common infectious diseases, vaccination is the standard of care. Annual vaccination for influenza and schedules for other infectious diseases are used in clinical practice to protect this population from severe illness.6 The reality, however, is that vaccines are less effective in the elderly, a phenomenon highlighted by immunologic responses to the Covid-19 vaccines.7 Healthcare providers historically have used, with limited success, higher-dose vaccines, alternate versions of vaccines, booster shots, or vaccines that include adjuvants in an effort to provoke a robust immune response in the aging.8

Taking this into account, we are compelled to look at life style factors that may offset some of the common infection symptoms that occur in the elderly. This study focused on exploring a population that was vaccinated against influenza; it then aimed to investigate whether a probiotic mixture could reduce common infectious disease symptoms.

Despite the compelling subject matter, this study was chal lenged in a few areas. The sample size was relatively small,

Research focusing on immunosenescence, or the way the aging immune system changes throughout the lifespan, has become a growing field in search of ways to support the aging process and potentially improve one’s later years.

with only 50 individuals total. Additionally, researchers did not assess (or did not report) baseline symptom scores. It appears they did not ask study participants if, on day 0 of the study, or during the 2 weeks before the study began, they had experienced any of the defined common infectious disease symptoms (respiratory symptoms included cold, cough, sneezing, sore/itchy throat, nasal obstruction, with or without fever; gastrointestinal symptoms included vomiting, diarrhea, abdominal pain; musculoskeletal symptoms included tension headaches, pain, weakness, stiffness, joint noises, decreased range of motion). Given the small sample size, the researchers may have been able to make a stronger argument for the efficacy of their intervention had they demonstrated a decrease in symptom scores over time in the intervention group and stability of scores in the placebo group.

Furthermore, musculoskeletal symptoms accounted for a large proportion of the symptoms reported in the placebo group. These symptoms are highly nonspecific for infection; for example, a study of influenza vaccine effectiveness defined influenza-like illness as “respiratory illness with sore throat, cough, sputum production, wheezing, or difficulty breathing, concurrent with one or more of the following: temperature above 37.2°C, chills, tiredness, headaches, or myalgia.”9 In this elderly cohort, many of these musculoskeletal symptoms are likely attributable to chronic osteoarthritis and deconditioning

associated with aging and, thus, may have been present at baseline. In a small study such as this, random allocation of a small number of participants who are more symptomatic at baseline could easily account for the positive findings.

The rate at which participants in the placebo group reported symptoms was quite high: 76% reported common infectious disease symptoms over the 8 weeks of the trial. For comparison, the influenza vaccine study cited above found that 23.7% of participants had a protocol-defined influenza-like illness and 51.4% had a respiratory illness over an approximately 6-month period. This further suggests that the symptoms collected were overly vague and that the placebo group may have included individuals more prone to reporting symptoms or who were more symptom atic at baseline.

Perhaps the most interesting element, particularly because this study is examining common infection symptoms as they may relate to influenza and common infections, is the curious omission of fever as a common infection symptom. Fever would be one of the first things a clinician would look for in a patient with an acute infection, and its absence as a standalone “common infectious disease symptom” in this study is puzzling. The authors may have included fever on their symptom checklist, but that is not clear from the article as written because the precise symptom checklist as seen by participants is not included in the text or in supplemental material.

Lastly, use of an objective assessment, such as respiratory viral PCR, to confirm that symptoms were due to infection would have markedly strengthened this study and would have likely been less costly than the laboratory parameters that were reported.

The authors report no change in salivary IgA concentrations with the study treatment. Fecal beta-defensin 2 increased in the probiotic group compared to baseline, though it did not increase in the placebo group compared to baseline. The more important analysis would have been a direct comparison of these levels between the probiotic and placebo groups at baseline and then after the intervention. Based on the

included figures, it appears that fecal beta-defensin 2 levels rose in both groups, but that the trend was statistically signif icant only in the probiotic group; this is an odd result to report. Unsurprisingly there were changes in the stool micro biome. It would be interesting to see whether stool micro biome changes predicted clinical symptoms, but given the size of the study, this analysis may be underpowered and does not appear to have been done.

Research on the connections between the gut microbiome, immunosenescence, vaccination, and common symptoms associated with infections is an emerging area. This study does seem to connect these areas, showing that there may be some effect, but initial findings will benefit from clarifica tion through future research with larger study sizes and more rigorous definition of clinical events.

Furthermore, although this research alone may not convince a clinician to prescribe or recommend probiotic formulations, clinicians may counsel patients to incorporate prebiotics, such as high-fiber vegetables, fruits, and legumes, and probiotics, such as fermented or cultured foods, into their diet. This method offers an avenue in which a patient may create a gut environment friendly to microbiota and then inoculate that environment with common bacterial strains found naturally in fermented foods.

REFERENCES

1 Gomaa EZ. Human gut microbiota/microbiome in health and diseases: a review. Antonie van Leeuwenhoek. 2020;113(12):2019-2040.

2 Cianci R, Franza L, Massaro MG, Borriello R, De Vito F, Gambassi G. The interplay between immunosenescence and microbiota in the efficacy of vaccines. Vaccines. 2020;8(4):636.

3 Wastyk HC, Fragiadakis GK, Perelman D, et al. Gut-microbiota-targeted diets modulate human immune status. Cell. 2021;184(16):4137-4153.e14.

4 Simpson RJ, Kunz H, Agha N, Graff R. Exercise and the regulation of immune func tions. Prog Mol Biol Transl Sci. 2015;135:355-380.

5 Akatsu H. Exploring the effect of probiotics, prebiotics, and postbiotics in strength ening immune activity in the elderly. Vaccines. 2021;9(2):136.

6 Centers for Disease Control and Prevention. Adult immunization schedule. https://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html#table-age. Accessed February 6, 2020.

7 Bajaj V, Gadi N, Spihlman AP, Wu SC, Choi CH, Moulton VR. Aging, immunity, and COVID-19: how age influences the host immune response to coronavirus infec tions? Front Physiol. 2021;11:571416.

8 Lord JM. The effect of aging of the immune system on vaccination responses. Hum Vaccin Immunother. 2013;9(6):1364-1367.

9 DiazGranados CA, Dunning AJ, Kimmel M, et al. Efficacy of high-dose versus stan dard-dose influenza vaccine in older adults. N Engl J Med. 2014;371(7):635-645.

What We Can Learn About Long-Covid from Chronic Fatigue Syndrome

An interview with Jacob Teitelbaum, MD

Chronic fatigue syndrome (CFS) is a poorly understood condition that affects up to 2.5 million Americans. Since the Covid-19 pandemic has left untold numbers of people with postviral symptoms that resemble CFS, interest in understanding the condition has been renewed. In a recent NMJ Podcast interview Natural Medicine Journal editor-in-chief Tina Kaczor, ND, FABNO, spoke with Jacob Teitelbaum, MD, who has studied postviral CFS for decades. This is a condensed version of their discussion.

Listen to the full podcast here.

Approximate listening time: 45 minutes

Tina Kaczor, ND, FABNO: How did you get into studying chronic fatigue?

Jacob Teitelbaum, MD: For those of us who have been doing integrative medicine for so long, we’ve been seeing chronic fatigue syndrome, fibromyalgia, and similar syndromes for years, and they’re often postviral. It’s really caught our eye now because it’s finally getting the attention that it’s probably deserved all along, but with Covid there’s a bright research light being shined on it.

Kaczor: Is there anything about long-Covid that’s different than other postviral syndromes?

Teitelbaum: Well to start with, long-Covid hasn’t been fully defined. It’s any symptom that persists. So your long-Covid can be cardiomyopathy, or if you’re having shock lung and you’re out of the game, or if you’re having trouble smelling or tasting, or if you have postviral CFS. So you want to break those 4 groups out because the treatments are quite different and may overlap a bit.

Kaczor: What is shock lung?

Teitelbaum: ARDS, acute respiratory distress syndrome. It is what happens to the lungs when people get Covid pneumonias. Once you have persistent problems, you have that shock lung or oxidative stress to the lung .

Kaczor: You mentioned some of the organ systems involved. How about the brain?

Teitelbaum: The brain fog is such an inherent part of postviral CFS. Now there are those with encephalopathic

disease. That’s quite different from brain fog. Most people will have brain fog, which is not a direct viral thing acting on the brain and causing almost a dullness. Your thinking is not sharp and quick-moving. That’s more encephalopathic. With brain fog, there’s difficulty with word finding, word substitu tion, and short-term memory, but it’s a very different feel.

Kaczor: You’ve talked about tripping a breaker. What do you mean by that?

Teitelbaum: When you see postviral chronic fatigue syndrome or CFS or fibromyalgia in general, these condi tions represent an energy crisis. The energy level has gotten low enough that the area using the most energy for its size goes offline. There’s an almond-sized area in the middle of the forehead of the brain called the hypothalamus. It is the circuit breaker and controls sleep. So people find that they’re sleeping all day, and then that morphs to can’t sleep at all. Or they get 3, 4 hours of sleep and can’t get restorative sleep. The hypo thalamus controls the hormone system, and those hormones are low across the board despite normal testing. It also controls autonomic function. Major, major issue, autonomic dysfunc tion in post-Covid, where people stand up and the blood goes out to their legs because of gravity and it stays there and doesn’t come back up to their brains. They start getting fuzzy and they start having issues. You can email me at Fatiguedoc@gmail. com for a home quiz that will help you diagnose and treat it. Ask for the 3 critical tools and you’ll also get some other intake questionnaires that will simplify things dramatically.

Kaczor: What you’re talking about is POTS, or Postural Orthostatic Tachycardia Syndrome. That’s probably the one that’s most talked about in my circles anyway.

Teitelbaum: That’s the current name. I’ve been around long enough that there are many names. For postviral with Covid, if you don’t have that on your radar, you’re not going to be able

to help people properly. It’s especially prominent with Covid more than other viruses.

Kaczor: Let’s say a person just had Covid and wants to address this as early as possible to prevent chronic fatigue from developing. What are some signs or symptoms to look out for?

Teitelbaum: Some people are more vulnerable to energy crises because they have nutritional deficiencies and are not sleeping, but especially people who try to push through the virus, who are thinking, “Well, I can’t rest, I’ve got to keep working.” They’re the ones more likely to blow a fuse. So if they come in showing fatigue, trouble sleeping, brain fog, and achiness, those are the big 4 that tell you that you’re heading toward a postviral fatigue path. You want to nip that in the bud.

Kaczor: I know you had a protocol, many years before Covid, for chronic fatigue. Can you speak about that?

Teitelbaum: The concept was that an increase in energy production will restore function and turn the circuit breaker back on, which is indeed what happens. The acronym we use is SHINE. S addresses sleep, H is hormonal issues, I is infections, N is nutritional support, and E is exercise. In a randomized, double-blind, placebo-controlled study we did, 91% of people improved with an average 90% increase in quality of life in the treatment group. So this is a very, very treatable disease.

Kaczor: With the system-wide energy crisis you are talking about, what tools in general would be indicated after a viral infection to bring down the body’s inflammatory state?

Pre-Conference: February 22, 2023 Conference + Exhibits: February 23-25, 2023 NEW YORK HILTON MIDTOWN, NY ihsymposium.com

D

N C E

Teitelbaum: Yes, Curaphen is a nice mix because that has a highly absorbed curcumin and Boswellia. I’ll also use Curapro if there’s not pain and Curaphen if there is pain. They’re remarkable for shutting inflammation down. You also got to go with a good multivitamin that’s high in anti oxidants, but especially B vitamins, magnesium, zinc, and vitamin A. Zinc is critical, especially in this virus because it will cause these chronic infections, and inflammation causes zinc loss. You’re aiming for 15 mg of zinc in your multivitamin and a half mg copper.

Kaczor: Moving to low-dose Naltrexone, what’s the mech anism behind it?

Teitelbaum: It helps address microglial activation in the brain. The microglial cells are like mild-mannered farmers tending the nerve cells. But then if they see something amiss, like an infection, they start attacking everything. It’s called microbial activation, and this triggers widespread damage. Low-dose Naltrexone, along with some other options, settles down microglial activation. It takes 8 to 10 weeks to start working. It is an important, immediate go-to for most autoimmune disease.

Kaczor: I’m excited that research dollars from the National Institutes of Health has increased from a pittance to over a billion dollars over the next 4 years to study what is going on. Will we do some basic research to understand how the body resolves inflammation?

Teitelbaum: Inflammation is only bad when it’s out of balance. A big part of that is a diet high in sugar, white flour, and grain-fed beef. But by the time something useful comes out from their $1.15 billion, they’ll be about as old as I am because they haven’t even designed a group to study. They’re just starting to do subsets. But we don’t have to wait for all that. You can help all these CFS patients now. For example, we already know how to get people sleeping again.

Kaczor: So there’s a ton of information that we’ve talked about. The big take-homes are to get people to take the time to recover and take it easy on themselves and maybe not just jump right back into the fray too quickly. Get their sleep going, get the inflammation down and their antioxidant status up, so that they’re recovering.

ABOUT THE EXPERT

JACOB TEITELBAUM, MD, is a board-certified internist and nationally known expert in the fields of chronic fatigue syndrome, fibromyalgia, sleep and pain. He has authored numerous books including the best-selling From Fatigued to Fantastic! (now in its 4th edition). He is the lead author of numerous studies on effective treatment for fibromyalgia and chronic fatigue syndrome, and one study on effective treatment of autism using NAET. He also developed the popular free smartphone app “Cures A-Z.” Teitelbaum lives in Kona, Hawaii.

Teitelbaum: Yes, and take a good multivitamin. Also, there’s a study we’ve just published using HRG80 red ginseng. In the study, stamina and energy both went up about 70% in postviral fatigue for severe cases, and about 60% of people improved quite dramatically. On my desk I have 1 bottle of chewable red ginseng energies. There is also a product that is being studied, but not available in the USA yet, called Recovery Factors. It is polypeptides that help with recovery too.

But yes, give patients a good multivitamin. Get them sleeping, rest, hydration. If they have post-Covid vaccine—I’ve seen almost as many of those as I’ve seen post-Covid where they get the CFS after—ivermectin works. I have no idea of the mechanism for why that works for a vaccine, but 27 mg a day for 4 days (or 5 days for really acute cases). Compounded is the easiest way to get it. Their postvaccine seems to clear up, but they often need to repeat courses. I have no idea why, but my old mentor used to say, “First see what it is. Don’t try to understand it or explain it, or you’ll never see anything you don’t expect. See what is, and then you can figure it out if you can.” This is one of those.

The views expressed in this interview are those of the guest and do not represent the views of Natural Medicine Journal, its staff, or its publishers.

REFERENCE

1 Epidemiology | Presentation and Clinical Course | Healthcare Providers | Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) | CDC. www.cdc.gov. Published April 27, 2021. https://www.cdc.gov/me-cfs/healthcare-providers/presen tation-clinical-course/epidemiology.html