DRAGONFLY KINGDOM NTERNATIONAL SERVICE AGENCY

Spices in the Apiaceae Family Represent the Healthiest Fatty Acid Profile: A Systematic Comparison of 34 Widely Used Spices and Herbs

Ramesh Kumar Saini, Awraris Derbie Assefa, and Young-Soo Keum

Abstract

Spices and herbs are well-known for being rich in healthy bioactive metabolites. In recent years, interest in the fatty acid composition of different foods has greatly increased. Thus, the present study was designed to characterize the fatty acid composition of 34 widely used spices and herbs. Utilizing gas chromatography (GC) flame ionization detection (FID) and GC mass spectrometry (MS), we identified and quantified 18 fatty acids. This showed a significant variation among the studied spices and herbs. In general, oleic and linoleic acid dominate in seed spices, whereas palmitic, stearic, oleic, linoleic, and α-linolenic acids are the major constituents of herbs. Among the studied spices and herbs, the ratio of n−6/n−3 polyunsaturated fatty acids (PUFAs) was recorded to be in the range of 0.36 (oregano) to 85.99 (cumin), whereas the ratio of PUFAs/saturated fatty acids (SFAs) ranged from 0.17 (nutmeg) to 4.90 (cumin). Cumin, coriander, fennel, and dill seeds represent the healthiest fatty acid profile, based upon fat quality indices such as the ratio of hypocholesterolemic/hypercholesterolemic (h/H) fatty acids, the atherogenic index (AI), and the thrombogenic index (TI). All these seed spices belong to the Apiaceae family of plants, which are an exceptionally rich source of monounsaturated fatty acids (MUFAs) in the form of petroselinic acid (C18:1n12), with a very small amount of SFAs.

Keywords: polyunsaturated fatty acids (PUFAs), erucic acid, petroselinic acid, fat quality indices, hypocholesterolemic fatty acids, atherogenic index (AI)

1. Introduction

Spices and herbs are a vital part of human nutrition around the world, especially in India, China, and southeastern Asian countries [1]. Spices and herbs are food adjuncts, traditionally used as flavoring, seasoning, coloring, and as a food preservative agent [1,2]. Moreover, spices and herbs are an exceptionally rich source of nutritionally important phenolic compounds [3]. These phenolic compounds are primarily responsible for the potent antioxidative, digestive stimulative, hypolipidemic, antibacterial, anti-inflammatory, antiviral, and anticancer properties of spices and herbs [4,5,6].

In general, the terms herbs and spices have more than one meaning. However, the most widely used are those that consider herbs to be derived from the green parts of a plant, such as a stem and leaves used in small amounts to impart flavor, whereas spices are obtained from seeds, buds, fruits, roots, or even the bark of the plants [2].

Fatty acids are the primary nutritional components found in edible seed oils [7]. Seed oils provide essential polyunsaturated fatty acids, linoleic acid (ω−6 or n−6), and α-linolenic acid (n−3) to humans and other higher animals. In the human body, linoleic acid give rise to n−6 very long-chain (VLC)-PUFA arachidonic acid, and α-linolenic acid converts to n−3 VLC-PUFA eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA, n−3). These n−6 and n−3 VLC-PUFAs plays key distinct roles in regulating body homeostasis. In general, n−6 VLC-PUFAs gives rise to proinflammatory mediators (eicosanoids) whereas n−3 VLC-PUFAs give rise to anti-inflammatory mediators. Thus, a higher amount of n−3 VLC-PUFAs in the body may protect from chronic diseases, including cancer, inflammatory, or cardiovascular diseases (CVD) [8]. Moreover, a diet with a high proportion of n−6 PUFAs (high ratio of n−6/n−3 PUFAs) cannot be considered beneficial to health, as n−3 PUFAs to n−3 VLC-PUFAs conversion occurs at a very low rate (e.g., 8% for EPA and less than 1% for DHA), and conversion is largely dependent upon the ratio of ingested n−6 (linoleic acid) and n−3 (α-linolenic) PUFAs [9]. In human hepatoma cells, this conversion is highest when these n−6 and n−3 acids are provided at a 1:1 ratio. Thus, the consumption of an appropriate amount of fats with a 1:1 n−6/n−3 PUFAs ratio, which was probably followed by our ancestors [10], may be considered beneficial.

Similar to the consumption of fats with a balanced ratio of n−6/n−3 PUFAs, growing evidence suggests that replacing saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) from plant sources may decrease the risk of CVD [11]. And with the health benefits associated with consumption of n−3 PUFAs and MUFAs, consumer interest is shifting towards foods with a low proportion of SFAs, a high proportion of MUFAs, and balanced n−6/n−3 PUFAs. Given this, it is necessary to characterize all the major and minor components of the diet to acquire a better estimate of the fatty acid composition of our food.

Spices and herbs are not a significant source of fatty acids, as they form a small part of the diet. However, a detailed and comparative study of the fatty acid composition of various spices and herbs may be useful to identify those with health-beneficial fatty acids. Considering these facts, this study aims to investigate the fatty acid composition of commercially available major spices and herbs utilizing gas chromatography-flame ionization detection and GC-mass spectrometry analysis. We used fatty acid composition data to study spices and herbs to determine their fat quality indices. We anticipate the results contained herein will contribute significantly to the identification of spices with a healthy fatty acid profile.

2. Materials and Methods

2.1. Plant Material, Reagents, and Standards

A total of 34 commercially packed spices and herbs (Table 1; 200–500 g each spice and herb from at least three different brands) were obtained from retail outlets in Seoul, Korea. The spice and herb samples of different brands were mixed in equal proportions (200–300 g total) to make a representative sample, ground into a fine powder using a 7010HG laboratory blender (Waring Commercial, Torrington, CT, USA), placed into an air-tight container, and stored at room temperature. The fatty acid standard mix (37 Component FAME Mix, CRM47885) was obtained from Merck Ltd., Seoul, Korea. The organic solvents used for the extraction of lipids were of high-pressure liquid chromatography (HPLC) grade, obtained from Samchun Chemical Co., Ltd., Seoul, Korea.

List of spices and herbs used in the present investigation (arranged according to botanical name).

2.2. Extraction of Crude Lipid Compounds

The crude lipids were extracted by using the previous method [12,13] with minor modification. Briefly, 0.6 g dehydrated and powdered spices and herb samples were precisely weighed and transferred to a 50 mL glass tube. In each tube, 150 mg sodium ascorbate and 22 mL (isopropyl alcohol/cyclohexane, 10:12, v/v) containing 0.075% butylated hydroxytoluene (BHT: w/v; antioxidant) were added, and the contents were subjected to bath sonication (JAC-2010; 300 w, 60 Hz, for 12 min) for efficient disintegration and complete extraction, followed by 15 h shaking (200 RPM at 22 °C) in a rotary shaker. Contents were centrifuged at 7000× g (12 min at 4 °C). The supernatant was collected, and pellets were extracted again with 30 mL cyclohexane. Supernatants from both extractions were pooled (total volume of ~50 mL) and partitioned with an equal volume of 1 M of sodium chloride (NaCl). The upper cyclohexane phase containing crude lipids were collected, filtered over anhydrous sodium sulfate, transferred to a 250-mL round-bottom flask, and vacuum-dried in a rotary evaporator at 30 °C. The crude lipids were recovered into 3 mL methanol/dichloromethane (DCM) (1:3, v/v) containing 0.1% BHT, transferred to a 5 mL glass vial fitted with a Teflon-lined screw cap, and stored at −20 °C. One milliliter of sample was used to prepare fatty acid methyl esters (FAMEs).

2.3. Preparation of Fatty Acid Methyl Esters (FAMEs)

The crude lipids extracted from the spices and herb samples were used to prepare the FAMEs, following the previously optimized method [14] with minor modification. Briefly, 1 mL of a crude lipids sample was transferred into a 5 mL glass vial fitted with a Teflon-lined screw cap. Contents were evaporated to dryness using a rotary evaporator at 30 °C. After evaporation, 3 mL of anhydrous methanolic-HCl (methanol/acetyl chloride, 95:5, v/v) was added and incubated for 2 h at 55 °C in a heat block. Samples were cooled in ice, and FAMEs were sequentially washed with 1M NaCl and 2% sodium bicarbonate (NaHCO3) and recovered in 4 mL hexane. A pinch of anhydrous sodium sulfate (Na2SO4) was added to the recovered sample (hexane) to absorb the traces of water. One milliliter of sample was filtered through a 0.45 μm PTFE syringe filter and transferred to a 1.5 mL autosampler vial for GC-FID and GC-MS analysis.

2.4. GC-FID and GC-MS Analysis of FAMEs

FAMEs were quantitatively analyzed with GC (Agilent 7890B, Agilent Technologies Canada, Inc., Mississauga, ON, Canada) equipped with an autoinjector, an FID, and an SP-2560 capillary column (100 m, 0.20 μm film thickness, 0.25 mm ID; Merck KGaA, Darmstadt, Germany). The injector and the detectors were maintained at 250 °C and 260 °C, respectively. The inlet flow was 2 mL/min with a constant pressure of 54 psi. The FID parameters of hydrogen (H2) fuel flow, airflow, and make flow (nitrogen, N2) were set to 30, 400, and 25 mL/min, respectively. The column oven temperature was kept at 140 °C for 5 min, then progressively increased to 240 °C for 25 min (linear temperature program 4 °C/min and held at 240 °C for 15 min [15]. The FAMEs were precisely identified by comparing them with the retention time with authentic standards. For a more accurate qualitative analysis, the mass spectra were also recorded using a GC-MS system (QP2010 SE; Shimadzu, Kyoto, Japan), following the optimized GC-FID analysis thermal program. The identity of FAMEs was confirmed by comparing their fragmentation pattern with authentic standards, and also by using the National Institute of Standards and Technology (NIST; U.S. Department of Commerce, Gaithersburg, MD, USA) mass spectrum database (NIST08 and NIST08s).

2.5. Calculation of Fat Quality Indices

We used the spice and herbs fatty acid profile to determine several nutritional parameters of lipids, including the ratios of PUFAs/monounsaturated fatty acids (MUFAs), PUFAs/saturated fatty acids (SFAs), the ratio of hypocholesterolemic/hypercholesterolemic (h/H) fatty acids, atherogenic index (AI), and thrombogenic index (TI) [16]. The ratio of h/H fatty acids, AI, and TI was calculated with the following equations [16]:

2.6. Statistical Analysis and Quality Control

We performed a total of six replicate extractions and analyses from each representative sample. The data were analyzed by one-way analysis of variance (ANOVA), and homogenous subsets (mean separation) were determined using Turkey HSD with a significance level of p < 0.05, utilizing the IBM statistical 25.0 software.

The method used for GC-FID quantification of FAMEs was validated recently [15].

3. Results and Discussion

3.1. Fatty Acids Composition

In the present study, 18 fatty acids were identified and quantified, utilizing GC-FID and GC-MS analyses (Table 2). The results, given in Table 2, show that oleic (C18:1n9) and linoleic acid (C18:2n6) are dominated in seed spices, and palmitic (C16:0), stearic, oleic, linoleic, and α-linolenic acid (C18:3n3) are the major constituents of herbs. An exception was myristic (C14:0) acid, which was 60.8% of total fatty acids in Myristica fragrans (nutmeg) seeds (Figure 1A,B). Surprisingly, myristic acid was just 1.59% of the total fatty acids in the M. fragrans (mace; Figure 1C) seed arils. The highest proportions of oleic acid (41.64–41.85%) were recorded in cardamon pods/capsules (Figure S1) and white pepper seeds (Table 2). The data of the fatty acid composition of cardamom pods and white pepper seeds are scarce. However, 40.6–49.2% of oleic acid has been reportedly extracted from cold-pressed cardamom seeds [17,18], which agrees with data obtained in the present study from whole cardamon pods.

(A) The gas chromatography (GC)-flame ionization detection (FID) profiles of fatty acid methyl esters (FAMEs) of nutmeg. (B) The GC-mass spectrum of dominating fatty acid (myristic acid) from nutmeg. (C) The GC-FID profiles of FAMEs of mace. The numbers, ...

Fatty acid composition of spices and herbs.

In the present study, a substantial amount of erucic (C22:1n9; 17.3%) and eicosenoic (20:1n9; gondoic acid; 8%) acids were exclusively recorded in white mustard (Sinapis alba; syn Brassica alba) seeds. Similarly, a significant amount of petroselinic acid (C18:1n12c; an isomer of oleic acid) was recorded only in Apiaceae family seeds.

Among the studied 34 spices and herbs, total fatty acids were recorded to be in the range of 2.3 (galangal root) to 130.32 mg/g (mace). The odd chain fatty acid, pentadecanoic (C15:0) acid, was recorded as being a minor constituent (1.18%) in the galangal root. Similarly, heptadecanoic (C17:0) was recorded at only 0.13–0.14% in cayenne pepper, allspice, and mace. In nutmeg (Myristica fragrans) seed hexane extract, Anaduaka et al. [19] reported a significant amount of (27%) heptadecanoic (C17:0; margaric) acid. However, in the present study, heptadecanoic acid is not detected in nutmeg seeds.

3.2. Black Pepper and White Pepper

Black pepper and white pepper are prepared from the fruits of Piper nigrum L., according to the harvesting time and inclusion of the outer skin. Black pepper is the dried immature but fully developed fruit, whereas white pepper consists of the mature fruit lacking the outer skin [20]. The fatty acid composition data of black and white pepper is scarce. In the present study, 28.57%, 14.95%, 26.61%, and 9.32% of palmitic, oleic, linoleic, and α-linolenic acid were recorded being in black pepper. In contrast, 22.55%, 41.64%, 17.19%, and 1.49% of palmitic, oleic, linoleic, and α-linolenic was reported as being in white pepper (Table 2). These observations show that oleic acid increases significantly, whereas the palmitic, linoleic, and α-linolenic acids decrease significantly during the maturation of pepper fruits.

3.3. Nutmeg and Mace

Nutmeg and mace spices are obtained from different parts of the same fruit of the nutmeg (Myristica fragrans; Myristicaceae) tree. Nutmeg is the dried kernel of the seed, whereas mace is the dried aril surrounding the seed [21]. Myristic acid’s name is derived from Myristica fragrans, from which it was first isolated [22]. In the present study, myristic acid was 60.8% of total fatty acids in nutmeg, followed by oleic (C18:1n9c; 13.4%), linoleic (C18:2n6c; 11.9%), and palmitic (C16:0; 8.94%) (Figure 1A). Surprisingly, in mace, linoleic acid was 33.7% of total fatty acids, followed by palmitic (30.6%) and oleic (28.0%). Myristic acid was only 1.59% of the total fatty acids (Figure 1C, Table 2). In the investigations of Al-Khatib et al. [23], myristic acid was recorded as being 79.7% of the total fatty acids in nutmeg. Kozłowska et al. [24] analyzed the fatty acids composition of plant seeds, including anise, coriander, caraway, white mustard, and nutmeg. They reported dominance of oleic (56.5%), palmitic (18.29%), and linoleic (13.6%) acids in nutmeg. These contrasting observations probably arose as these authors reported only above C16 fatty acids. Myristic acid is widely used in the food industry as a flavor ingredient. It is approved as a pharmaceutical excipient by the Food and Drug Administration (FDA) and declared generally recognized as safe (GRAS) by various regulators [25].

3.4. Erucic Acid in White Mustard

Mustard (Sinapis alba; syn Brassica alba) seeds are well known for the occurrence of a substantial amount of erucic and eicosenoic acid [24]. In the present study, white mustard seeds were found containing 17.3% and 8.0% of erucic and eicosenoic acid, respectively (Figure 2A, Table 2). High intake of erucic acid is considered harmful for cardiac health [26]. The panel on contaminants in the food chain established a tolerable daily intake (TDI) of 7 mg/kg body weight (BW) for erucic acid based on a no-observed adverse effect level (NOAEL) for myocardial lipidosis in rats and pigs [26]. Considering the 43 mg of total fatty acids/g of white mustard seeds, consumption of 100 g of seeds may provide 7.31 mg of erucic acid. The intake of erucic acid from white mustard used as food condiments in daily food preparations is far below the TDI and is safe for consumption.

(A) The gas chromatography (GC)-flame ionization detection (FID) profiles of fatty acid methyl esters (FAMEs) of white mustard seeds. (B,C) The GC-mass spectrum of eicosenoic acid and erucic acid from white mustard seeds. (D) The GC-FID profiles of FAMEs ...

Petroselinic acid (C18:1n12c; an isomer of oleic acid) is the major component of the lipid constituent of Apiaceae family seeds [27,28]. In a previous study [27] of dill (Anethum graveolens) seeds, 87.2% of total fatty acids were composed of petroselinic acid. Similarly, in celery (Apium graveolens), coriander seeds (Coriandrum sativum), and fennel seeds (Foeniculum vulgare), petroselinic acid was recorded as being 56.1%, 72.8%, and 31.32% of total fatty acids. In agreement with the present study, we have also recorded the 50.4%, 49.4%, 62.1%, and 63.3% of petroselinic acid in dill, coriander celery, and fennel seeds, respectively (Table 2). And a similar high amount of petroselinic acid was reported to be in the seeds of other Apiaceae family plants, such as caraway (Carum carvi, 34.1%) and cumin (Cuminum cyminum; 49.9%). In seeds of different varieties of caraway, Reiter et al. [28] recorded 33.5–42.5% of petroselinic acid, which is in agreement with the present study. Petroselinic acid possesses potent anti-inflammatory and antiaging properties by reducing the metabolites of arachidonic acid [29]. And owing to its anti-aging properties, petroselinic acid is widely used in cosmetics or dermatological compositions [29]. Surprisingly, petroselinic acid was not detected in herbs (leaves) of the Apiaceae family member parsley (Petroselinum crispum). In the parsley herb, hexadecatrienoic (C16:3n3) was reported to be 17.7% of the total fatty acids (Figure 2D), whereas no other spices were found to contain this fatty acid. Parsley has been previously classified as a “16:3” plant owing to the presence of a significant amount of hexadecatrienoic acid in photosynthetic tissues, which is part of primitive lipid metabolism [30].

3.5. Fat Quality Indices

The present study is based on the fatty acid composition of 34 spices and herbs. We evaluated them for fat quality indices, including the n–6/n–3 ratio, AI, TI, and h/H fatty acid ratios (Table 3). Among the studied spices and food condiments, the ratio of n–6/n–3 PUFAs was found to be in the range of 0.36 (oregano) to 85.99 (cumin). In view of health benefits associated with the consumption of n−6/n−3 PUFAs ratio of 0.5–2.0 (nearest to 1:1), lipids obtained from leaf spices, including tarragon (0.76), bay leaf (1.33), basil (0.55), marjoram (0.75), parsley (0.48), white mustard (0.95), sage (0.86), and thyme (0.52) can be considered to be beneficial. In general, the high occurrence of α-linolenic acids compared to linoleic acid is responsible for the low n−6/n−3 ratio in leaves (photosynthetic tissue).

The fat quality indices of lipids of spices and herbs.

In view of the high risk of CVD and other chronic diseases that are associated with the dietary intake of SFAs [11], fats with a PUFAs/SFAs ratio lower than 0.45 are not advised for diet [31]. In the present study, PUFAs/SFAs ratios ranged from 0.17 (nutmeg) to 4.90 (cumin). Low PUFAs/SFAs ratios of 0.17 in nutmeg lipids are the result of the dominance of myristic acid (an SFA; Figure 1A), whereas in the case of cumin, linoleic acid is dominant over SFAs. In addition to the nutmeg, low PUFAs/SFAs ratios (<0.44) were recorded from galangal root (0.29), lemongrass (0.24), rosemary (0.28), and sage (0.38) because of the occurrence of a substantial amount of palmitic acid (Figure S2).

Fats with lower AI and TI and higher ratios of h/H fatty acids are recommended for minimizing the risk of CVD [32]. In the present study, a significant difference was recorded for AI, TI values as well as h/H fatty acids among the studied spices and herbs. The lowest significant values of the AI (0.06) and the highest ratios of h/H fatty acids (17.0) were obtained from cumin seeds (Table 3, Figure 3), because of the presence of a low amount of atherogenic lauric, myristic, and palmitic fatty acids, and high amounts of hypocholesterolemic C18:1 MUFAs and PUFAs. Whereas the lowest significant values of TI (white mustard, due to the low contents SFAs and high content of PUFAs.

(A) Illustrations showing the high content of healthy monounsaturated (MUFAs) and polyunsaturated fatty acids (PUFAs) in cumin, compared to low contents of MUFAs and PUFAs, and high contents of saturated fatty acids (SFAs) in nutmeg. (B) Arrangements ...

Overall, based on a higher ratio of h/H fatty acids and their lower AI and TI values, cumin, coriander, fennel, and dill spices have the healthiest fatty acid profiles (Figure 3). These spices belong to the Apiaceae family. White mustard also represents a higher ratio of h/H fatty acids and lower values of AI and TI. However, it contains a substantial amount of erucic acid.

In Figure 3, cumin, coriander, fennel, and dill spices top the fat quality indices, the ratio of h/H fatty acids, AI, and TI. However, the occurrence of a very low proportion of α-linolenic acid (a n−3 PUFA; 0.35–0.85%) and a fairly good amount of linoleic acid (a n–6 PUFA; 19.60–33.34%) in these spices, give rise to the high ratio of n–6/n–3 PUFAs (24.02–85.99), which is substantially higher than the recommended ratio of 1:1. Considering this, the culinary use of these spices can be recommended with n–3 PUFA rich components to obtain the overall n–6/n–3 PUFAs ratio of 1:1.

Previously, we had analyzed the total phenolic contents (TPC) and antioxidant activities of 39 spices and herbs (including the 34 spices and herbs investigated in the present study) and found that cloves possess the highest antioxidant activities, followed by allspice, cinnamon, oregano, and marjoram [33]. The high antioxidant activities of these spices and herbs were probably the results of the richness of phenolic compounds, as the antioxidant activities showed a good correlation (0.835–0.966) with TPC. In contrast, in the present study, cumin, coriander, fennel, and dill spices showed the healthiest fatty acid profile among the 34 spices and herbs. These observations show that the selection of healthy spices and herbs may vary with nutrient requirements. Thus, in the present study, cumin, coriander, fennel, and dill spices are the recommendations based on the fatty acid profile. However, other spices and herbs might be richer in other health-beneficial dietary components.

4. Conclusions

Spices belonging to Apiaceae family plants (cumin, coriander, fennel, and dill) are an exceptionally rich source of monounsaturated fatty acids (MUFAs) in the form of petroselinic acid, a good amount of polyunsaturated fatty acids (PUFAs; linoleic acid), and a small amount of saturated fatty acids. And, with high proportions of MUFAs and PUFAs, the Apiaceae family spices top the fat quality indices, particularly in terms of a higher ratio of hypocholesterolemic/hypercholesterolemic fatty acids, and lower values of the atherogenic index and the thrombogenic index (Figure 3).

Acknowledgments

This paper was supported by the KU Research Professor Program of Konkuk University, Seoul, Korea.

Supplementary Materials

The following are available online at https://www.mdpi.com/article/10.3390/foods10040854/s1, Figure S1: (A) The gas chromatography (GC)-flame ionization detection (FID) profiles of fatty acid methyl esters (FAMEs) of cardamom. (B) The GC-mass spectrum of dominating fatty acid (Palmitic acid); Figure S2. (A–C) The gas chromatography (GC)-flame ionization detection (FID) profiles of fatty acid methyl esters (FAMEs) of lemongrass, rosemary, and Sage. The GC-mass spectrum of dominating fatty acid (Palmitic acid). The numbers, 4, 7, 9, 11, and 14 correspond to peak numbers illustrated in Table 1. BHT: Butylated hydroxytoluene (A synthetic antioxidant used during lipid extraction).

Author Contributions

Conceptualization, R.K.S. and A.D.A.; methodology, R.K.S. and A.D.A.; software, R.K.S. and A.D.A.; validation, R.K.S. and A.D.A. and Y.-S.K.; formal analysis, R.K.S.; investigation, R.K.S.; resources, Y.-S.K.; data curation, R.K.S. and A.D.A.; writing—original draft preparation, R.K.S.; writing—review and editing, A.D.A. and Y.-S.K.; visualization, Y.-S.K.; supervision, Y.-S.K.; project administration, R.K.S.; funding acquisition, R.K.S. All authors have read and agreed to the published version of the manuscript.

Funding

This paper was supported by the KU Research Professor Program of Konkuk University, Seoul, Republic of Korea and “The APC was supported by Konkuk University research fund (2021A0190061)”.

Conflicts of Interest

The authors declare no conflict of interest.

Footnotes

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Article information

Foods. 2021 Apr; 10(4): 854.

Published online 2021 Apr 14. doi: 10.3390/foods10040854

PMCID: PMC8071036

PMID: 33920058

Ramesh Kumar Saini,1 Awraris Derbie Assefa,2 and Young-Soo Keum1,*

Andreas Eisenreich, Academic Editor and Bernd Schaefer, Academic Editor

1Department of Crop Science, Konkuk University, Seoul 05029, Korea; rk.ca.kuknok@7991inias

2National Agrobiodiversity Center, National Institute of Agricultural Sciences, Rural Development Administration, Jeonju 54874, Korea; rk.aerok@sirarwa

*Correspondence: rk.ca.kuknok@lanoitar

Received 2021 Mar 8; Accepted 2021 Apr 12.

Copyright © 2021 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

This article has been cited by other articles in PMC.

Articles from Foods are provided here courtesy of Multidisciplinary Digital Publishing Institute (MDPI)

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Iranian Journal of Psychiatry

Tehran University of Medical Sciences

Abstract

Despite the overwhelming prevalence of anxiety disorders in modern society, medications and psychotherapy often fail to achieve complete symptom resolution.

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Anxiety

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A complementary approach to medicating symptoms is to address the underlying metabolic pathologies associated with mental illnesses and anxiety. This may be achieved through nutritional interventions.

In this perspectives piece, we highlight the roles of the microbiome and inflammation as influencers of anxiety. We further discuss the evidence base for six specific nutritional interventions: avoiding artificial sweeteners and gluten, including omega-3 fatty acids and turmeric in the diet, supplementation with vitamin D, and ketogenic diets. We attempt to integrate insights from the nutrition science-literature in order to highlight some practices that practitioners may consider when treating individual patients.

Notably, this piece is not meant to serve as a comprehensive review of the literature, but rather argue our perspective that nutritional interventions should be more widely considered among clinical psychiatrists. Nutritional psychiatry is in its infancy and more research is needed in this burgeoning low-risk and potentially high-yield field........

Indexed for NIH/Frontiers In Psychiatry by Dragonfly Kingdom Library

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7907178/

Dandelions have a reputation as both a granter of wishes and a dreaded weed and lawn nuisance. However, did you know that dandelion root is loaded with nutrients and boasts a variety of benefits to your health — just like dandelion greens and dandelion tea?

What is dandelion root good for? This plant is low in calories, yet high in fiber as well as antioxidants, vitamin K, vitamin A and vitamin C. Research even suggests it can help reduce cancer growth, lower cholesterol levels and support liver function.

In addition to being rich in many vitamins and minerals that promote a strong immune system, dandelion is also readily available, easy to add to your diet and bursting with a signature, peppery flavor.

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What Is Dandelion?

Dandelions, also known as Taraxacum officinale, are a type of flowering plant native to Europe, Asia and North America.

As a member of the daisy family of plants, dandelions are related to dahlias, thistle, ragweed, lettuce, artichokes and sunflowers.

Dandelions produce many small yellow flowers, called florets, which collectively form one flower head. Once it has finished flowering, the flower head dries out, the florets drop off and a seed head is formed.

The dandelion seeds are then naturally dispersed by the wind … or those looking to score a free wish.

Dandelion Nutrients:

Although dandelion is often overlooked as just a pesky weed, it can actually be a useful addition to both your kitchen and your medicine cabinet. Many parts of the dandelion plant are edible, including the roots, leaves, seeds and flowers.

Both the root and greens are packed with health-promoting properties and can be used to make everything from dandelion tea to super-nutritious salads. Not only is this plant high in vitamins and antioxidants — such as silymarin, silibinin, curcumin, berberine and resveratrol — it also contains potassium, magnesium, zinc, iron and choline.

Historical Uses:

Just like other roots, such as burdock and ashwagandha, dandelion root also has a rich history of use in traditional medicine. In fact, the origins of dandelion as a natural remedy can be traced all the way back to 659 B.C. in ancient China. It was also used in Arabic, Welsh and European medicine and was eaten raw or made into a juice or tonic.

Traditional uses of the dandelion ranged from promoting better digestion to healing the liver. Some Native American tribes chewed on dandelion root to relieve pain, while others steamed the leaves and applied topically to ease sore throats.

Why are dandelions sometimes called “pee the beds”? In some countries, including Scotland and France, these plants earned the nickname pee-the-beds, or pissenlit in French, due to their natural diuretic effects that can cause increased urination.

Dandelion Root Benefits

What does dandelion do to your body? Here’s more about what research has shown us regarding dandelion root benefits. ....... https://draxe.com/nutrition/dandelion-root/

Abstract

Antioxidants and diets supplemented with foods high in oxygen radical absorbance capacity (ORAC) reverse age-related decreases in cerebellar β-adrenergic receptor function. We examined whether this effect was related to the antioxidant capacity of the food supplement and whether an antioxidant-rich diet reduced the levels of proinflammatory cytokines in the cerebellum. Aged male Fischer 344 rats were given apple (5 mg dry weight), spirulina (5 mg), or cucumber (5 mg) either in 0.5 ml water by oral gavage or supplied in the rat chow daily for 14 d.

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Electrophysiologic techniques revealed a significant decrease in β-adrenergic receptor function in aged control rats. Spirulina reversed this effect. Apple (a food with intermediate ORAC) had an intermediate effect on cerebellar β-adrenergic receptor physiology, and cucumber (low ORAC) had no effect, indicating that the reversal of β-adrenergic receptor function decreases might be related to the ORAC dose. The mRNA of the proinflammatory cytokines tumor necrosis factor-α (TNFα) and TNFβ was also examined. RNase protection assays revealed increased levels of these cytokines in the aged cerebellum.

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Spirulina and apple significantly downregulated this age-related increase in proinflammatory cytokines, whereas cucumber had no effect, suggesting that one mechanism by which these diets work is by modulation of an age-related increase in inflammatory responses. Malondialdehyde (MDA) was measured as a marker of oxidative damage. Apple and spirulina but not cucumber decreased MDA levels in the aged rats. In summary, the improved β-adrenergic receptor function in aged rats induced by diets rich in antioxidants is related to the ORAC dose, and these diets reduce proinflammatory cytokine levels.

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Impaired antioxidant defense mechanisms and increases in reactive oxygen species and reactive nitrogen species are postulated to be causative factors in aging-related functional declines and in neurodegenerative diseases (Harman, 1956; Leibovitz and Siegel, 1980; Ames et al., 1993). Increasing evidence suggests that inflammatory processes are linked to oxidative damage in the CNS. Injection of the antioxidant enzyme superoxide dismutase decreases inflammation in some animal model systems.

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Antioxidants such as vitamins E, C, and β-carotene enhance some parameters of immune function when added to isolated immune cellsin vitro or when given as supplements to humans or animalsin vivo (Han and Meydani, 2000). Despite extensive evidence of the anti-inflammatory effects of antioxidants, little is known about the underlying molecular mechanisms.

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One potential mechanism is the effect of antioxidants on the production of immunoregulatory molecules such as cytokines. Cytokines are induced in response to brain injury and can mediate and inhibit cellular injury and repair. Many clinical studies report increased cytokine expression in the CSF or in postmortem brain tissue of patients that have suffered stroke or brain injury. Several lines of evidence indicate that proinflammatory cytokines such as interleukin-1 (IL-1), tumor necrosis factor (TNF), and transforming growth factor-β increase with aging (Lynch, 1998; Knoblach et al., 1999

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Several studies have examined antioxidants and their effects in aged animals and humans. Diets enriched in fruits and vegetables that have a high antioxidant capacity as measured by oxygen radical absorbance capacity (ORAC) (Cao et al., 1997) fed to rats for periods as short as 2 weeks to 2 months starting at 18 months of age can reverse the age-related onset of some behavioral and neurochemical deficits (Gould and Bickford, 1997; Joseph et al., 1999; Bickford et al., 2000). Much of the evidence supporting the beneficial role of fruits and vegetables to health comes from epidemiological literature.

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The traditional common diet of the Mediterranean region, a diet high in fruits and vegetables, is associated with a significant (17%) reduction in overall mortality in the elderly from these regions (Willet et al., 1995). Recent studies with vitamin E indicate that high doses slow the progression of certain aspects of Alzheimer's disease (Sano et al., 1997). Vitamin E 1300 IU Oil

The nature of the protective effects of specific nutrients found in fruits and vegetables, such as β-carotene, vitamin C, and vitamin E, however, is unknown.

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A single factor is not likely to be the only effective agent in these studies. With few exceptions, a single nutrient is not packaged into a single food, and it is possible that combinations of nutrients have greater protective effects than each nutrient alone.......

Indexed for Journal of Neuroscience by Dragonfly Kingdom Library

https://www.jneurosci.org/content/22/14/6114

Abstract

An in-treatment web-based survey was conducted in 2005 with 50 New York World Trade Center rescue and recovery workers, volunteers, and area residents and workers who were treated with Ayurvedic herbs for post-9/11 symptoms.

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The survey documented pretreatment efforts at symptom relief, post-treatment symptom impact, and the context for using the herbal intervention. Herbal treatment was administered and monitored by a private non-profit organization.

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The natural detoxification and immune-strengthening program consists of 4 herbal supplements developed by an Ayurvedic physician. A minimum 6-month basic program was recommended, but many participants continued to 1 year and longer. All 50 respondents reported high incidence of alleviation of previously intractable symptoms, chiefly respiratory symptoms, fatigue, and depression.

Indexed for NIH Pubmed by Dragonfly Kingdom Library 

https://pubmed.ncbi.nlm.nih.gov/18251318/

Abstract

Disturbed epigenetic mechanisms, which developmentally regulate gene expression via modifications to DNA, histone proteins, and chromatin, have been hypothesized to play a key role in many human diseases. Recently it was shown that engineered nanoparticles (NPs), that already have a wide range of applications in various fields including food production, could dramatically affect epigenetic processes, while their ability to induce diseases remains poorly understood. Besides the obvious benefits of the new technologies, it is critical to assess their health effects before proceeding with industrial production. In this article, after surveying the applications of NPs in food technology, we review recent advances in the understanding of epigenetic pathological effects of NPs, and discuss their possible health impact with the aim of avoiding potential health risks posed by the use of nanomaterials in foods and food-packaging.

Keywords: Epigenetic effects; Impact on health; Nanomaterials in food; Nanoparticles; Risk assessment.

Indexed for NIH Pubmed by Dragonfly Kingdom Library

https://pubmed.ncbi.nlm.nih.gov/25554528/

Copyright © 2014 Elsevier Ltd. All rights

It is rare to find a patient with electrical sensitivities who does not already have multiple on-

going sensitivities to chemicals, volatiles and particulates.

ELECTRICAL SENSITIVITIES

and the

ELECTRICAL ENVIRONMENT

Cyril W. Smith, Ph.D.

E:mail: cyril.smith@which.net

A shortened and edited version of notes written for and in cooperation with The

Breakspear Hospital, Hemel Hempstead, HP2 4FD, U.K. The writer has been helping

their electrically hypersensitive patients since 1982

.

What are Electrical Sensitivities?

Many persons suffer from sensitivities to certain foods and environmental chemicals which

cause them discomfort, or even in extreme cases prevent them from functioning in any

effective manner. Even the most minute amounts of these substances may on occasions

‘trigger’ reactions which are specific to each individual. Warnings regarding nuts, peanuts or

gluten are commonly found displayed on food products. When a sensitivity reaction occurs,

some regulatory system within the body has ceased to function properly and gives alarm

signals, calling for an unjustified panic reaction. Usually, it is the autonomic nervous system

(ANS) which is the first to become compromised in this way. This system controls all the

involuntary body functions. Thus, any part or function of the body might become affected by

the same allergen acting in different people which is why such effects do not show up in

medical statistics.

Those who have already acquired several chemical hypersensitivities and which are ‘on-

going’, are at particular risk of acquiring electrical sensitivities as an additional problem. The

allergen ‘triggering effect’ may transfer from a minute amount of some chemical in the

environment to some patient-specific frequency of an electromagnetic field in the

environment. Usually, it is the same patient symptoms that continue to be ‘triggered’. It is

the frequency of the electromagnetic field that matters, once some patient-specific threshold of

intensity or field strength has been exceeded. The range of effective coherent frequencies

extends from below a thousand seconds per cycle (circadian rhythms) through audio- and

radio- and microwave-frequencies to visible light. All these effects are ‘non-thermal’: the

electrical power is insufficient to produce any significant heating. It is the frequency that

matters. In technical terms, it is the spectral power density or the watts per cycle of bandwidth

of the radiation which matters. The more precise the frequency – the less power is needed to

produce an effect.

Germany has introduced the WHO International Classification of Diseases Code T78.4 for

‘Chemical-Sensitivity Syndrome Multiple’, against which this can be reported and statistics

collected. There is no electrical equivalent WHO Classification to date but it would seem

reasonable for these cases to be recorded as a complication of the multiple chemical

sensitivities which precede the electrical sensitivities. Sweden regards electrical sensitivity as

a disability with the implication that all public places must be fit for the electrically sensitive

disabled person to be in.

The Electrical Environment

Such persons may experience problems from the natural electrical environment beyond what

is normal such as the influence of light on melatonin levels. Electrical or acoustic (even sub-

audio) frequencies from approaching weather fronts or thunderstorms may become

troublesome. Eventually, there may be a hypersensitivity to sunlight.

Fluorescent lighting and lasers at check-outs may make shopping difficult, particularly if

inhalants such as chemicals on in-store fabrics provide an initial chemical sensitisation. The

patient may experience problems when near any electrical equipment such as power lines,

radio- TV- or mobile phone transmitters, tape or DVD-recorders, computers, mobile phones,

satellites or in fact any one of the multitude of electronic devices in the modern environment.

It is not necessary for an electrical device to be active, any passive resonant circuit may

suffice; this could be the resonant frequency of a row of metal railings in the street. Persons

may become aware of actually having electrical devices malfunction when they handle them

or, even when in their vicinity.

The female characteristic is towards chronic sensitivities appearing at an early stage, resulting

in being labelled as “over-anxious”; the male characteristic is for no reaction until the onset of

a sudden and disabling crash which may result in the person becoming completely unable to

function normally.

The hazard of chronic over-exposure to electrical frequencies is one of adaptation to

symptoms triggered by a particular pattern of frequencies until they become indistinguishable

from a disease condition. The problem seems to arise when the frequency pattern of a toxic

chemical in the body matches that of the person’s electrical environment. It is the frequencies

in the electrical environment which makes the body think it is under chemical attack

Typical Subjective Symptoms Relating to Electrical Sensitivities

Drowsiness, malaise and headache, mood swings, tearfulness and eye pain, poor

concentration, vertigo and tinnitus, numbness and tingling, nausea and flatulence,

convulsions, noise sensitivity, alteration in appetite, visual disturbances, restlessness,

blushing.

Clinical Observations Relating to Electrical Sensitivities

Changes in respiration, heart rate changes (heart rate variability analysis is a good indicator of

the status of the ANS), eye pupil dilation, perspiration or lack of it, muscular weakness, loss

of visual acuity, speech or writing difficulties, loss of consciousness, convulsions.

At the Breakspear Hospital, about 10% of all patients with chemical, nutritional or particulate

sensitivities had acquired electromagnetic sensitivities. Tests often showed stress coming

from some common environmental frequency such as the power supply (50Hz in UK, 60 Hz

in North America) or the 2.45 GHz frequency of microwave cookers and other devices using

this frequency.

Patients’ reactions were triggered over a very wide range of frequencies for which at first

there was no recognisable pattern. Then it was realised that 7.8 Hz often appeared.

Measurements quickly revealed that 7.8 Hz was the endogenous frequency of the heart

acupuncture meridian. The endogenous frequencies of other acupuncture meridians also

appeared when these were under stress. The frequencies on acupuncture meridians are very

precise; for 53 heart meridian frequencies from 38 patients, the mean was 7.788 Hz (standard

deviation ± 0.92%). This frequency is used in some therapeutic or environment protection

devices and it occurs in radiation from the Schumann Bands in the upper atmosphere to

which we are all exposed.

Sensitivities to Foods and Chemicals

About 1-in-6 of a ‘population’ is usually considered to have some degree of impaired function

due to an allergic reaction to the environment or to food. Repeated exposure to a frequency

while a person is reacting to some other allergic trigger may link that specific sensitivity

pattern to that frequency, so that the same reaction is triggered on encountering either the

frequency or the allergen on a subsequent occasion. In general, the patient’s pattern of

response is the same whether the trigger is chemical, biological, particulate, nutritional or

electrical – it is characteristic of the patient.

Exposure to pesticides or herbicides seems to enhance or even create electrical sensitivities.

Formaldehyde is a very good sensitizer. Ionising radiation exposure (e.g. long-haul flights)

represents an additional stress factor. A few persons may become hypersensitive to light,

some to sunlight, or to the light of the mercury vapour spectrum, which is superimposed on

the emission from fluorescent tubes and energy-saving lamps.

Dental fillings may cause problems due to electrolytic currents between amalgam fillings containing different mixtures of metals or, between fillings and surrounding tissue. Patients

have been seen with black stains on the palate due to the electrolytic transport of mercury.

Amalgam-to-tissue contacts may detect environmental frequencies such as radio transmissions

just like a cat’s-whisker crystal set. There has been a case where a dentist heard music coming

from a patient’s mouth. The mercury toxicity frequency and a mobile phone frequency

unfortunately happen to stress the parasympathetic branch of the autonomic nervous system.

A common feature of electrical hypersensitivity is that its sufferers complain vigorously that

nobody does anything for them, such as turning off an electrical source which they know is

“triggering” their reactions but, which seems to have no effect on anyone else. When a

hypersensitivity to sunlight is acquired, the futility of this approach is realised but perhaps not

before the sufferer has become almost paranoid about these problems.

Treatment

When patients have acquired a high degree of sensitivity to many factors in foods and/or the

chemical environment (multiple-sensitivities), they are very likely to have acquired an

abnormal sensitivity to their electrical environment as a part of this ‘package’ of symptoms.

It is rare to find electrical sensitivities without on-going chemical sensitivities. This electrical

sensitivity can become so severe that a person becomes incompatible with technology and

unable to function in the modern environment. Electrical sensitivity is not mutually exclusive

of other clinical conditions; it can co-exist with and even trigger physical or mental illness.

Electrical sensitivities make diagnosis and therapy more difficult. Medications may produce

abnormal responses or side effects, even chronic sensitisation to the electrical environment.

A therapy for alleviating allergic reactions is called provocation/neutralisation

therapy. It was developed from earlier work in the USA by Dr. Joseph Miller of Mobile,

Alabama, and further developed at the Environmental Health Center, in Dallas, Texas, by Dr.

W. J. Rea and at the Breakspear Hospital, Hemel Hempstead, England by its Medical

Director, Dr. Jean Monro. This therapy relies on successive serial dilutions of the substance

having in sequence the effects of stimulating and/or quelling the reactions that they produce.

This therapy is not a substitute for eventually reducing the total body loading of triggering

substances to a level that the individual can cope with which can be done by simultaneously

increasing the rate of detoxification and reducing the rate of toxin intake until the body can

function normally, assuming that the enzyme systems for detoxification are still intact.

However, while this can produce an alleviation of the symptoms and thereby assist achieving

eventual normalisation, it may not be possible to achieve this without some change in the

patient’s lifestyle. It is also labour-intensive and therefore expensive.

The general concept introduced by Dr. W. J. Rea is to seek to reduce the total body load of

stressors. Which stress factors one seeks to reduce may be a matter of choice although some

stresses are involuntary through exposure to the general environment. Dr. Rea has

demonstrated the reality of electrical sensitivities in double-blind trials1

. The equivalent

therapy for alleviating reactions to electrical frequencies involves trying to find one or more

frequencies which will turn-off the body’s abnormal frequency sensitivity. This is not a

cure but it can help stabilise the body for more effective allergy therapy. As foods and

chemicals sensitivities are brought under control and the body detoxifies itself, the electrical

sensitivities usually disappear as well. Symptoms usually disappear in the reverse order to

their appearance. However, it is worth noting that if a person is working or sleeping in a zone

of ‘geopathic stress’, which may be electrical in origin, then their problems may persist and

resist therapies.

Reducing the Impact of the Electrical Environment

The sensitive person is best able to determine what affects them. It is impossible to get away

from the natural electromagnetic radiation from the sun, the ionosphere, the weather and the

geomagnetic field. It is almost impossible to get away from man-made electromagnetic radiation. Persons who find a deep canyon or go to the ‘out-back’ still get zapped when a

satellite comes over the horizon. The best indicators for safer places are – mobile phones do

not work, TV reception is poor and there are no overhead lines.

In the home, electricity supply meters emit large fields and may be located in a passage on the

other side of the wall from a bed-head. From where the power supply reaches the house, its

cable may run on an outside wall but, close to a bed. Power lines on overhead poles may act

as antennae for radio and microwave transmissions and channel them into the house wiring. It

is good practice to turn off all non-essential electrical circuits at night. Power frequencies

may have the same effect as daylight in the arctic summer depressing the level of melatonin

(an anti-cancer agent). Some biologically based shielding may be provided by pine trees

which have terpene problems, cacti or spider-plants.

The power supply frequencies are in effect impossible to shield with any practical measures.

Higher frequencies can be shielded by metal wire mesh, metallised fabric or aluminium foil,

although these may act as mirrors to reflect the radiation elsewhere. They can also reflect

self-radiation emitted by a person having an allergic reaction making it even worse. A very

sensitive person may react to a quantum component of the electromagnetic field called the

magnetic vector potential and this cannot be shielded2

.

It is rare to find electrical sensitivities without previous and ongoing chemical sensitivities. If

a person is sensitised chemically, the electrical sensitivity can be enhanced. Remember that

electronic equipment emits chemical fumes and as these may be a trigger for reactions so they

need to be ventilated. For example, a person may tolerate the electromagnetic radiation from

a television set if it is enclosed in a glass-fronted box ventilated to the outside keeping fumes

from the hot plastic out of the room.

Computers have different clock frequencies usually specified in terms of their speed of

operation. These frequencies will be sub-divided in the process of carrying out the various

computational functions. It may be possible to find a model/manufacturer whose equipment is

tolerated. The flat screen displays are likely to have less emission. The pulses emitted when a

mobile phone dials-up a number can imprint frequencies into the head if it is held against the

ear before dialling is complete.

The eye can also be a pathway for frequencies to enter the body such as when viewing TV or a

computer. Most acupuncture meridians are stimulated/stressed while viewing a light source

flashing at a frequency equal to the endogenous frequency of the meridian. Frequencies

greater than 0.05 Hz and less than 47 kHz have this effect as do strong visual patterns and

colours. The body as a whole is sensitive to resonances in its environment, so metal structures

or even electronic equipment which is not switched on may cause problems.

Computer keyboards can have a long cable or an infrared optical link to the computer unit

enabling the latter to be kept at a distance. A whole building or public area may be fitted out

with a wire-less internet link which cannot be avoided. There is software which enables one to

dictate to a computer, so that the process of typing in a lot of text can be circumvented; only

error correction and editing need be done at the keyboard.

Conclusion

It is rare to find a patient with electrical sensitivities who does not already have multiple on-

going sensitivities to chemicals, volatiles and particulates. To avoid becoming electrically

sensitive, one must be careful about acquiring a body load of chemicals which happen to be

toxic to you because your body cannot get rid of them quickly. Then, if the frequency pattern

of such substances happens to match a pattern of frequencies in your electrical environment

this will make the body think it is under further chemical attack. That is why only some

people are affected by their electrical environment. Engineers (chemical or electrical) work to

specifications, unless they are told that certain environmental frequency patterns cause. 

1. For evidence that electromagnetic field sensitivity actually does exist and can be elicited under

environmentally controlled double-blind conditions with 100% reactions to an active frequency and 0% to

the placebos, see: Rea WJ. Pan Y. Fenyves EJ. Sujisawa I. Suyama H. Samadi N. and Ross GH.

“Electromagnetic Field Sensitivity”, Journal of Bioelectricity 10(1&2): 241-256 (1991).

 2. Smith C.W. Is a living system a macroscopic quantum system? Frontier Perspectives, 7(1), 9-15 (1998),

(Temple University, Philadelphia, 1997 lecture to Frontier Sciences Department).

[Congressional Record Volume 144, Number 141 (Friday, October 9, 1998)]

[Extensions of Remarks]

[Pages E1992-E1994]

From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]

MULTIPLE CHEMICAL SENSITIVITY

______

HON. BERNARD SANDERS

of vermont

in the house of representatives

Thursday, October 8, 1998

Mr. SANDERS. Mr. Speaker, I rise today to discuss the issue of

Multiple Chemical Sensitivity as it relates to both our civilian

population and our Gulf war veterans.

Multiple Chemical Sensitivity or MCS is a chronic condition marked by

heightened sensitivity to multiple different chemicals and other

irritants at or below previously tolerated levels of exposure.

Sensitivity to odors is often accompanied by food and drug intolerance,

sensitivity to sunlight and other sensory abnormalities, such as

hypersensitivity to touch,

[[Page E1993]]

heat and-or cold, and loud noises. MCS is often accompanied by impaired

balance, memory and concentration.

As a member of the Human Resources Subcommittee, which has oversight

jurisdiction for the Veterans' Affairs, I have been involved in the

issue of Gulf war illness and Multiple Chemical Sensitivity. I have

been concerned for many years about the role that chemicals may be

playing on human health, not only in Gulf war veterans and their

families, but in civilian society as well. I have talked to many people

who are suffering symptoms not dissimilar from the symptoms that our

Persian Gulf veterans are experiencing because of chemicals in their

homes or workplaces.

As has been well-documented, the military theater in the Persian Gulf

was a chemical cesspool. Our troops were exposed to chemical warfare

agents, leaded petroleum, widespread use of pesticides, depleted

uranium and burning oil wells. In addition, they were given a myriad of

pharmaceuticals as vaccines. Further, and perhaps most importantly, as

a result of a waiver from the FDA, hundreds of thousands of troops were

given pyridostigmine bromide. Pyridostigmine bromide, which was being

used as an anti-nerve agent, had never been used in this capacity

before. In the midst of all this, our troops were living in a hot,

unpleasant climate and were under very great stress.

The Department of Defense and the Department of Veterans Affairs have

downplayed the presence of Multiple Chemical Sensitivity in Gulf war

veterans. In the very beginning, the Defense Department and Veterans'

Affairs actually denied that there was any problem whatsoever with our

veterans' health. Then, after finally acknowledging that there was a

problem, they concluded that the problem was in the heads of our

soldiers--of psychological origin. The DOD and the VA responded very

poorly to our veterans' concerns. Tragically, our veterans were

discounted. They were called malingerers.

Ever so slowly, the truth about chemical exposure in the Persian Gulf

has begun to surface. On July 24, 1997, the Defense Department and the

Central Intelligence Agency gave us their best estimate--that as many

as 98,910 American troops could have been exposed to chemical warfare

agents due to destruction of ``the Pit'' in Khamisiyah, an Iraqi

munitions facility.

Not waiting for the DOD and VA, many other Federal, State, and local

government agencies have recognized the existence of Multiple Chemical

Sensitivity. I want to submit for the Record the latest ``Recognition

of Multiple Chemical Sensitivity'' newsletter which lists the U.S.

Federal, State, and local government authorities, U.S. Federal and

State courts, U.S. workers' compensation boards, and independent

organizations that have adopted policies, made statements, and-or

published documents recognizing Multiple Chemical Sensitivity

disorders.

Recognition of Multiple Chemical Sensitivity

Multiple Chemical Sensitivity or MCS is a chronic condition

marked by heightened sensitivity to multiple different

chemicals and other irritants at or below previously

tolerated levels of exposure. Sensitivity to odors is often

accompanied by food and drug intolerances, photosensitivity

to sunlight and other sensory abnormalities, such as

hypersensitivity to touch, heat and/or cold, and loud noises

and impaired balance, memory and concentration. MCS is more

common in women and can start at any age, but usually begins

in one's 20's to 40's. Onset may be sudden (from a brief

high-level toxic exposures) or gradual (from chronic low-

level exposures), as in ``sick buildings.'' The syndrome is

defined by multiple symptoms occuring in multiple organ

systems (most commonly the neurological, gastrointestinal,

respiratory, and musculoskeletal) in response to multiple

different exposures. Symptoms may include chronic fatigue,

aching joints and muscles, irritable bowel, difficulty

sleeping and concentrating, memory loss, migraines, and

irritated eyes, nose, ears, throat and/or skin. Symptoms

usually begin after a chronic or acute exposure to one or

more toxic chemical(s), after when they ``spread'' to other

exposures involving unrelated chemicals and other irritants

from a great variety of sources (air pollutants, food

additives, fuels, building materials, scented products,

etc.). Consistent with basic principles of toxicology, MCS

usually can be improved, although not completely cured,

through the reduction and environmental control of such

exposures. Many different terms have been proposed in medical

literature since 1869 to describe MCS syndrome and possibly

related disorders whose symptoms also wax and wane in

response to chemical exposures.

Alternate Names Proposed for MCS

Acquired Intolerance to Solvents, Allergic Toxemia,

Cerebral Allergy, Chemical Hypersensitivity Syndrome,

Chemical-Induced Immune Dysfunction, Ecological Illness,

Environmental Illness or ``EI,'' Environmental Irritant

Syndrome, Environmentally Induced Illness, Environmental

Hypersensitivity Disorder, Idiopathic Environmental

Intolerances or ``IEI,'' Immune System Dysregulation,

Multiple Chemical Hypersensitivity Syndrome, Multiple

Chemical Reactivity, Total Allergy Syndrome, Toxic Carpet

Syndrome, Toxin Induced Loss of Tolerance of ``TILT,'' Toxic

Response Syndrome, 20th Century Disease.

Disorders Associated With Single or Multi-Organ Chemical Sensitivity

Akureyri Disease (coded as EN), Asthma, Cacosmia, Chronic

Fatigue Syndrome, Disorders of Porphyrin Metabolism, [Benign

Myalgic] Encephalomyelitis, Epidemic Neuromyastenia (EN),

Fibromyalgia Syndrome, Gulf War Syndrome, Icelandic Disease

(coded as EN), Mastocytosis, Migraine, Neurasthenia, Royal

Free [Hospital] Disease, Sick Building Syndrome, Silicone

Adjutant Disease, Systemic Lupus Erythematosus, Toxic

Encephalopathy.

Listed alphabetically below are the U.S. Federal, State,

and local government authorities, U.S. Federal and State

courts, U.S. workers' compensation boards, and independent

organizations that have adopted policies, made statement,

and/or published documents recognizing MCS disorders under

one name or another as a ligitimate medical condition and/or

disability. An introductory section summarizes recognition or

MCS in peer-reviewed medical literature, and the last section

lists upcoming MCS conferences as well as past conferences

sponsored by Federal Government agencies.

The exact meaning of ``recognition'' varies with the

context as each listing makes clear. Recognition by a court

of law, for example, usually refers to a verdict or appeal in

favor of an MCS plaintiff, while recognition by government

agencies varies tremendously--from acknowledgement of the

condition in publications and policies to research funding

and legal protection of disability rights.

Recognition of MCS by 25 Federal Authorities

U.S. Agency for Toxic Substances & Disease Registry in a

unanimously adopted recommendation of the ATSDR's Board of

Scientific Counselors, which calls on the ATSDR to ``take a

leadership role in the investigation of MCS'' [1992, 24

pages, R-1]. To coordinate interagency research into MCS,

the ATSDR co-chairs the Federal Work Group on Chemical

Sensitivity, which it convened for the first time in 1994

(see below). The ATSDR has helped organize and pay for

three national medical conferences on MCS: sponsored by

the National Academy of Sciences in 1991, the Association

of Occupational and Environmental Clinics in 1991, and the

ATSDR in 1994. The combined proceedings of these three

conferences are reprinted in Multiple Chemical

Sensitivity, A Scientific Overview, ed. Frank Mitchell,

Princeton NJ: Princeton Scientific Publishing, 1995 (609-

683-4750 to order). ATSDR also contributed funding to a

study conducted by the California Department of Health

Services to develop a protocol for detecting MCS outbreaks

in toxic-exposed communities via questionnaires and

diagnostic tests (see entry below on California Department

of Health Services). Officially, however, ATSDR has not

``established a formal position regarding this syndrome''

[1995, 1 page, R-2].

U.S. Army, Medical Evaluation Board on US Army Form 3947

(from the U.S. Army Surgeon General), Army Medical Evaluation

Board certified a diagnosis of ``Multiple Chemical

Sensitivities Syndrome'' for a Persian Gulf veteran on 14

April 1993 [1 page, R-3]. MCS is defined on this form as

``manifested by headache, shortness of breath, congestion,

rhinorrhea, transient rash, and incoordination associated

with exposure to a variety of chemicals.'' The Board's report

further recognizes that this patient's particular MCS

condition began approximately in April 1991 (while the

patient was serving in the Gulf and entitled to base pay),

that the condition did not exist prior to service, and that

it has been permanently aggravated by service. At least five

other active duty Persian Gulf veterans have been diagnosed

by the Army with MCS, as reported by the Persian Gulf

Veterans coordinating Board in ``Summary of the Issues

Impacting Upon the Health of Persian Gulf Veterans,'' [3

March 1994, 4 page excerpt, R-4]. The Army Medical Department

also has requested funding for a research facility to study

MCS (reported in an Army information paper on ``Post Persian

Gulf War Health Issues,'' 16 November 1993).

U.S. Congress in a VA/HUD Appropriations Bill for FY1993

signed by President Bush in 1992 appropriating ``$250,000

from Superfund funds for chemical sensitivity workshops.''

These funds were used by the U.S. Agency for Toxic Substances

and Disease Registry (see above) to co-sponsor scientific

meetings on MCS with various other organizations [1992, 3

page excerpt, R-5] and support an MCS study (see California

State Department of Health Services below). For FY 1998,

Vermont Congressman Bernard Sanders proposed and Congress

appropriated $800,000 to start a new 5-year civilian agency

research program into MCS among Gulf War veterans. Congress

also requested that the administration report back by January

1998 on how it planned to spend the funds (text of

appropriations is quoted in report; see below: U.S.

Department of Health Services, Agency for Health Care Policy

and Research).

U.S. Consumer Product Safety Commission, U.S. Environmental

Protection Agency, American Lung Association, and American

Medical Association (jointly) in a jointly published booklet

entitled Indoor Air Pollution

[[Page E1994]]

An Introduction for Health Professional [US GPO 1994-523-217/

81322] under the heading ``What is `multiple chemical

sensitivity' or `total allergy'?, these organizations state

that ``The current consensus is that in cases of claimed or

suspected MCS, complaints should not be dismissed as

psychogenic, and a thorough workup is essential.'' The

booklet is prefaced by the claim that ``Information provided

in this booklet is based upon current scientific and

technical understanding of the issues presented . . .``

[1994, 3 page excerpt, R-6]

U.S. Department of Agriculture, Forest Service in its Final

Environmental Impact Statement on ``Gypsy Moth Management

in the United States: a cooperative approach'', people

with MCS are mentioned as a ``potential high risk group''

who should be given advance notification of insecticide

treatment projects via ``organizations, groups and

agencies that consist of or work with people who are

chemically sensitive or immunocompromised.'' MCS also is

discussed in an appendix on Human Health Risk Assessment

(Appendix F, Volume III of V) under both ``Harzard

Identification'' and ``Groups at Special Risk'' [1995, 11

page excerpt and 1 page cover letter from John Hazel, the

USDA's EIS Team Leader, to Dr. Grace Ziem of MCS Referral

& Resources, R-130].

U.S. Department of Education in the enforcement by its

Office of Civil Rights of Section 504 of the Rehabilitation

Act of 1973 which requires accommodation of persons with

``MCS Syndrome'' via modification of their educational

environment, as evidenced by several ``agency letters of

finding'' (including San Diego (Calif) Unified School

District, 1 National Disability Law Reporter, para. 61, p.

311, 24 May 1990; Montville (Conn.) Board of Education, 1

National Disability Law Reporter, para. 123, p. 515, 6 July

1990; and four letters (along with an individualized

environment management program) in the case of the Arminger

children of Baltimore County, MD [in 1991, 1992, 1993 and

1994; 20 pages total, R-7]. These accommodations also are

required under the terms of Public Law 94-142, now known as

the Individuals with Disabilities Education Act (CFR34 Part

300). The Department of Education as a whole, however, has no

formal policy or position statement on the accommodation of

students with MCS.

U.S. Department of Energy, Oak Ridge National Laboratory in

being the lead sponsor of the 11th Annual Life Sciences

Symposium on ``Indoor Air and Human Health Revisited.'' This

1994 conference was co-sponsored by the US Environmental

Protection Agency and Martin Marietta Energy Systems'

Hazardous Waste Remedial Action Program. The proceedings are

published in Indoor Air and Human Health (Gammage RB and

Berven BA, editors, Boca Raton FL: CRC Lewis Publishers,

1996) and contain several peer-reviewed papers of critical

relevance to MCS by DoE, EPA and other federally funded

researchers. (4 page excerpt with table of contents, R-175)

U.S. Department of Health and Human Services (HHS), Agency

for Health Care Policy and Research in a ``Report to Congress

on Research on Multiple Chemical Exposures and Veterans with

Gulf War Illnesses'' by agency administrator Dr. John

Eisenberg (who is also the acting Assistant Secretary for

Health). Dr. Eisenberg proposes spending $300,000 in 1998 for

a ``consensus building'' and research planning conference,

$400,000 for research into the health effects of chemical

mixtures, and $100,000 for an Interagency Coordinator in the

Office of Public Health and Science [January 1998, 7 pages

including MCS R&R press release, R-168]. Congress requested

the report in 1998, as part of an $800,000 appropriation for

a new civilian research into MCS (see U.S. Congress, above).

U.S. Dept. of HHS, National Institute on Deafness and Other

Communication Disorders in the funding of MCS-related

olfactory research by its Chemical Senses Branch since

NIDCD's creation in 1988; including $29,583,000 in fiscal

year 1998. The Chemical Senses Branch supports both basic and

applied research, with most of its funds going to just five

``chemosensory research centers'': the Connecticut

Chemosensory Clinical Research Center (860-679-2459), Monell

Chemical Senses Center (215-898-6666), Rocky Mountain Taste

and Smell Center (303-315-5650), State University of New York

Clinical Olfactory Research Center (315-464-5588), and

University of Pennsylvania Smell and Taste Center (215-662-

6580). Free information is available from NIDCD Information

Clearinghouse, 800-241-1044.

U.S. Dept. of HHS, National Institute of Environmental

Health Sciences in ``Issues and Challenges in Environmental

Health,'' a publication about the work of NIEHS, research

priorities are proposed for ``hypersensitivity diseases

resulting from allergic reactions to environmental

substances'' [NIH 87-861, 1987, 45 pages, R--8]. It is not

clear from the context if this statement was meant to include

or exclude MCS, since the condition was still thought by some

at the time to be an allergic-type reaction. In 1992, the

director Dr. Bernadine Healy responded in detail to an

inquiry from Congressman Pete Stark about the scope of NIEHS

research into MCS: ``It is hoped that research conducted at

NIEHS will lead to methods to identify individuals who may be

predisposed to chemical hypersensitivities. . . . NIH

research is directed toward the understanding of the effect

of chemical sensitivities on multiple parts of the body,

including the immune system.'' [1992, 3 pages, R-9]. In 1996,

director Dr. Kenneth Olden wrote US Senator Bob Graham that

``NIEHS has provided research support to study MCS. . . .

NIEHS has also supported a number of workshops and meetings

on the subject.'' [15 April 1996, 2 pages, R-101]. Dr. Olden

also states that ``Pesticides and solvents are the two major

classes of chemicals most frequently reported by patients

reporting low level sensitivities as having initiated their

problems.''

U.S. Department of Health and Human Services, National

Library of Medicine . . . in the 1995 Medical Subject

Headings (MESH) codes used to catalog all medical references,

which started using Multiple Chemical Sensitivity (and its

variations) as a subject heading for all publications indexed

after October 1994 [3 pages excerpt, R-10].

U.S. Department of Health and Human Services, Office for

Civil Rights (OCR) . . . in the final report by the Regional

Director (of Region VI) regarding OCR's investigation of an

ADA-related discrimination complaint filed by a patient with

MCS against the University of Texas M.D. Anderson Cancer

Center for failing to accommodate her disability and thereby

forcing her to go elsewhere for surgery. Prior to completion

of the investigation and the issuance of any formal

``findings,'' the OCR accepted a proposal from the Univ. of

Texas to resolve this complaint by creating a joint

subcommittee of the cancer center's Safety and Risk

Management committees. This subcommittee's three tasks (as

approved by the OCR) are to ``identify a rapid response

mechanism which could be triggered by any patient registering

a complaint or presenting a special need which is environment

related; develop a `protocol' outlining steps to be taken to

resolve environmental complaints by patients . . . ; and

inform the medical staff through its newsletter of the

mechanism and the protocol so that they will better

understand how to address such questions or concerns.'' The

OCR has placed the M.D. Anderson Cancer Center ``in

monitoring'' pending completion and documentation of these

changes, but it may initiate further investigation if M.D.

Anderson fails to complete this process within the 13 months

allowed. [27 March 1996, 11 pages, R-99]

U.S. Department of Health and Human Services, Social

Security Administration . . . in enforcement of the Social

Security Disability Act (see Recognition of MCS by Federal

Courts, below), and in the SSA's Program Operations Manual

System (POMS), which includes a section on the ``Medical

Evaluation of Specific Issues--Environmental Illness''

stating that ``evaluation should be made on an individual

case by case basis to determine if the impairment prevents

substantial gainful activity'' [SSA publication 68-0424500,

Part 04, Chapter 245, Section 24515.065, transmittal #12,

1998, 1 page excerpt, R-11]. In 1997, the U.S. District Court

in Massachusetts required Acting SSA Commissioner John

Callahan to spell out the agency's position on MCS in a

formal memo to the court (31 October 1997, 2 pages, R-164;

see Creamer v. Callahan below, under Recognition of MCS by US

Federal Court Decisions). With this memo, SSA now officially

recognizes MCS ``as a medically determinable impairment'' on

an agency wide basis. MCS is also recognized in several

``fully favorable'' decisions of the SSA's Office of Hearing

and Appeals: in case #538-48-7517, in which the

administrative law judge, David J. Delaittre, ruled that

``the claimant has an anxiety disorder and multiple chemical

sensitivity,'' with the latter based in part on the fact that

``objective [qEEG] evidence showed abnormal brain function

when exposed to chemicals'' [1995, 7 pages, R-12]; in case

#264-65-5308, in which the administrative law judge, Martha

Lanphear, ruled that the claimant suffered severe reactive

airways disease secondary to chemical sensitivity and that

this impairment prevented her from performing more than a

limited range of light work [1996, 8 pages, R-120]; in case

#239-54-6581, in which the administrative law judge, D. Kevin

Dugan, ruled that the claimant suffered severe impairments as

a result of pesticide poisoning, including ``marked

sensitivity to airborne chemicals,'' which prevent her from

``performing any substantial gainful activity on a sustained

basis [1996, 4 pages, R-135]; in case #024-40-2499, in which

the administrative law judge, Lynette Diehl Lang, recognized

that the claimant suffered from severe MCS and could not

tolerate chemical fumes at work (as a result of overexposure

to formaldehyde in a state office building), as a result of

which he was awarded both disability benefits and

supplemental security income [1995, 8 pages, R-140]; in case

#184-34-4849, in which administrative law judge Robert Sears

ruled that the claimant suffered from ``extreme environmental

sensitivities,'' and particularly ``severe intolerance to any

amount of exposure to pulmonary irritants'' [11 June 1996, 7

pages, R-156]; and in case #256-98-4768, in which the

administrative law judge, Frank Armstrong, classified the

claimant's ``dysautonomia triggered by multiple chemical

sensitivities'' as severe and said it ``prevents the claimant

from engaging in substantial gainful activity on a sustained

basis'' [18 March 1997, 8 pages, R-157].

____________________

High fat diet influences T cell homeostasis and macrophage phenotype to maintain chronic inflammation

Udai P Singh, Pegah Mehrpooya, Bam Marpe, Narendra P Singh, E. Angela Murphy, Manoj K Mishra, Bob L Price, Mitzi Nagarkatti and Prakash S Nagarkatti

J Immunol May 1, 2016, 196 (1 Supplement) 197.15;

Abstract

Over the past 20 years obesity has become a global health problem affecting the life expectancy of people at epidemic proportions. Obesity is characterized as a state of low-grade chronic inflammation that influences the development and progression of many chronic diseases. A unique role of T cells in adipose tissue has been shown in the initiation and regulation of the inflammatory cascade. However, the mechanisms responsible for the obesity-associated inflammation are not known. We investigated how high fat diet may influence homeostatic expansion of T cells, macrophage behavior and inflammation. High fat diet consumption alters the body weight, fat mass, and lean mass of mice when compared with those on a normal diet. The high fat diet increases the frequency of CD44+ and TCR αβ+T cells in the epididymal adipose tissues as compared with a normal diet. In mice consuming a high fat diet, we also found a significant increase in the frequency of CXCR3+ activated CD8T cells, CD8+KLRG1 cells and pro-inflammatory cytokines in mucosal and epididymal adipose tissues. High fat diet consumption resulted in greater than 2 fold changes in 85 gene and 142 miRs in epididymal adipose immune cells. Among these, ten inflammatory, obesity miRNAs and genes were validated by RT-PCR analysis. Pathway analysis also validated that differentially regulated miRNAs and gene target mRNAs are associated with T cell homeostatic expansion and macrophage function. Taken together, these results indicate that high fat diet modulates T cell homeostatic proliferation, macrophage phenotype, inflammatory miRNAs and genes to sustain inflammation. This study supports a key role of T cell homeostasis and macrophages to induce inflammation during high fat diet-induced obesity.

Copyright © 2016 by The American Association of Immunologists, Inc

Keywords: immune system, vitamin D, vitamin E, n-3 PUFA, probiotics, green EGCG, zinc

Introduction

The main functions of body's immune system are to protect the host against infection from pathological microorganisms, to clear damaged tissues, and to provide constant surveillance of malignant cells that grow within the body. Additionally, the immune system develops appropriate tolerance to avoid unwanted response to healthy tissues of self or harmless foreign substances. There is considerable heterogeneity among individuals in the vigor of their immunological function, largely owing to factors such as genetics, environment, lifestyle, nutrition, and the interaction of these factors. Nutrition as a modifiable factor in impacting immune function has been studied for several decades, and the research in this field has developed into a distinguished study subject called nutritional immunology. As with other bodily systems, the immune system depends on adequate nutrients to function properly. It is well-documented that nutritional status is closely associated with immunity and host resistance to infection. There is little argument that deficiency in both macronutrients and micronutrients causes immune function impairment, which can be reversed by nutrient repletion. Nutritional deficiencies are still prevalent in less developed regions and are a main contributor to a high incidence of morbidity and mortality from infectious diseases. Even in developed countries where general nutritional deficiencies are rare, nutrition issues such as specific nutrient deficiencies, less ideal diet composition, and excess calorie consumption are still a challenging reality......

Indexed for NIH by Dragonfly Kingdom Library

https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6340979/

Major international research efforts are being made to fight this trend – including an initiative at London’s Francis Crick Institute, where two world experts, James Lee and Carola Vinuesa, have set up separate research groups to help pinpoint the precise causes of autoimmune disease, as these conditions are known.

“Numbers of autoimmune cases began to increase about 40 years ago in the west,” Lee told the Observer. “However, we are now seeing some emerge in countries that never had such diseases before.

For example, the biggest recent increase in inflammatory bowel disease cases has been in the Middle East and east Asia. Before that they had hardly seen the disease.”

Autoimmune diseases range from type 1 diabetes to rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis. In each case, the immune system gets its wires crossed and turns on healthy tissue instead of infectious agents.......... 

Highlights

 Endogenous retrovirus sensing is required for commensal-

specific immunity

 Reverse transcription inhibition impairs commensal-induced

immunity in the skin

 cGAS/STING signaling in keratinocytes is required for skin

immunity to the microbiota

 Enhanced endogenous retrovirus expression promotes

microbiota-induced inflammation

Endogenous retroviruses promote homeostatic

and inflammatory responses to the microbiota

Djalma S. Lima-Junior,1,11 Siddharth R. Krishnamurthy,1,2,11 Nicolas Bouladoux,1,2 Nicholas Collins,1 Seong-Ji Han,1

Erin Y. Chen,3 Michael G. Constantinides,1,10 Verena M. Link,1,4 Ai Ing Lim,1 Michel Enamorado,1 Christophe Cataisson,5

Louis Gil,2 Indira Rao,1,6 Taylor K. Farley,1,7 Galina Koroleva,4 Jan Attig,8,9 Stuart H. Yuspa,5 Michael A. Fischbach,3

George Kassiotis,8,9 and Yasmine Belkaid1,2,12,*

1Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, National

Institutes of Health, Bethesda, MD 20892, USA

2NIAID Microbiome Program, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA

3Department of Bioengineering and ChEM-H, Stanford University, Stanford, CA 94305, USA

4NIH Center for Human Immunology, Bethesda, MD 20896, USA

5In Vitro Pathogenesis Section, Laboratory of Cancer Biology and Genetics, Center for Cancer Research, National Cancer Institute, National

Institutes of Health, Bethesda, MD 20892, USA

6Immunology Graduate Group, University of Pennsylvania, Philadelphia, PA 19104, USA

7Kennedy Institute of Rheumatology, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of

Oxford, Roosevelt Drive, Oxford OX3 7FY, UK

8Retroviral Immunology, The Francis Crick Institute, 1 Midland Road, London NW1 1AT, UK

9Department of Medicine, Faculty of Medicine, Imperial College London, London W2 1PG, UK

10Present address: Department of Immunology and Microbiology, Scripps Research, La Jolla, CA 92037, USA

11These authors contributed equally

12Lead contact

*Correspondence: ybelkaid@niaid.nih.gov

https://doi.org/10.1016/j.cell.2021.05.020

SUMMARY

The microbiota plays a fundamental role in regulating host immunity. However, the processes involved in

the initiation and regulation of immunity to the microbiota remain largely unknown. Here, we show that the

skin microbiota promotes the discrete expression of defined endogenous retroviruses (ERVs). Keratino-

cyte-intrinsic responses to ERVs depended on cyclic GMP-AMP synthase (cGAS)/stimulator of interferon

genes protein (STING) signaling and promoted the induction of commensal-specific T cells. Inhibition of

ERV reverse transcription significantly impacted these responses, resulting in impaired immunity to the mi-

crobiota and its associated tissue repair function. Conversely, a lipid-enriched diet primed the skin for

heightened ERV- expression in response to commensal colonization, leading to increased immune re-

sponses and tissue inflammation. Together, our results support the idea that the host may have co-opted

its endogenous virome as a means to communicate with the exogenous microbiota, resulting in a multi-

kingdom dialog that controls both tissue homeostasis and inflammation..........

Abstract

Introduction SARS-CoV-2 vaccination is effective in preventing severe COVID-19, but efficacy in reducing viral load and transmission wanes over time. In addition, the emergence of novel SARS-CoV-2 variants increases the threat of uncontrolled dissemination and additional antiviral therapies are urgently needed for effective containment. In previous in vitro studies Echinacea purpurea demonstrated strong antiviral activity against enveloped viruses, including SARS-CoV-2. In this study, we examined the potential of Echinacea purpurea in preventing and treating respiratory tract infections (RTIs) and in particular, SARS-CoV-2 infections.

Methods 120 healthy volunteers (m,f, 18 – 75 years) were randomly assigned to Echinacea prevention or control group without any intervention. After a run-in week, participants went through 3 prevention cycles of 2, 2 and 1 months with daily 2’400mg Echinacea purpurea extract (Echinaforce®, EF). The prevention cycles were interrupted by breaks of 1 week. Acute respiratory symptoms were treated with 4’000 mg EF for up to 10 days, and their severity assessed via a diary. Naso/oropharyngeal swabs and venous blood samples were routinely collected every month and during acute illnesses for detection and identification of respiratory viruses, including SARS-CoV-2 via RT-qPCR and serology.

Results Summarized over all phases of prevention, 21 and 29 samples tested positive for any virus in the EF and control group, of which 5 and 14 samples tested SARS-CoV-2 positive (RR=0.37, Chi-square test, p=0.03). Overall, 10 and 14 symptomatic episodes occurred, of which 5 and 8 were COVID-19 (RR=0.70, Chi-square test, p>0.05). EF treatment when applied during acute episodes significantly reduced the overall virus load by at least 2.12 log10 or approx. 99% (t-test, p<0.05), the time to virus clearance by 8.0 days for all viruses (Wilcoxon test, p=0.02) and by 4.8 days for SARS-CoV-2 (p>0.05) in comparison to control. Finally, EF treatment significantly reduced fever days (1 day vs 11 days, Chi-square test, p=0.003) but not the overall symptom severity. There were fewer COVID-19 related hospitalizations in the EF treatment group (N=0 vs N=2).

Discussion/Conclusion EF exhibited antiviral effects and reduced the risk of viral RTIs, including SARS-CoV-2. By substantially reducing virus loads in infected subjects, EF offers a supportive addition to existing mandated treatments like vaccinations. Future confirmatory studies are warranted.

Indexed for CSH BMJ YALE  by Dragonfly Kingdom Library 

https://www.medrxiv.org/content/10.1101/2021.12.10.21267582v1