Oral Vit C has been reported to reduce viral infections or improve the symptoms or shorten the disease duration like cold or flu. In a 30-day training camp, a group of 1444 young and healthy military recruits in Korea, 695 subjects received high dose oral Vit C (6000 mg daily) and 749 subjects did not receive Vit C. The Vit C group showed a 0.8 times lower risk of getting common cold than the control group[1]. In an earlier study, a group of 463 students between 18 and 32 years of age were divided into 2 groups, the Vit C group of 252 students, when they reported upper respiratory viral infection signs and symptoms, were given 1000 mg of Vit C hourly for the first 6 hours and then followed by 1000 mg 3 times daily. The Control group, when they showed signs and symptoms, were given pain relievers and decongestants. The authors concluded that the symptoms decreased by 85% with the mega-dose Vit C[2].

1. Kim TK, Lim HR, Byun JS  Vitamin C supplementation reduces the odds of developing a common cold in Republic of Korea Army recruits: randomised controlled trial. BMJ Mil Health. 2020 Mar 5. pii: bmjmilitary-2019-001384. doi: 10.1136/bmjmilitary-2019-001384. [Epub ahead of print]

2.  Gorton HC, Jarvis K. The effectiveness of vitamin C in preventing and relieving the symptoms of virus-induced respiratory infections. J Manipulative Physiol Ther. 1999 Oct;22(8):530-3.

1.

Hospital treatment of serious and critical COVID-19 infection with high-dose Vitamin C

Shanghai Expert Consensus on Covid-19 Treatment

The City of Shanghai Expert Consensus on Comprehensive Treatment
of COVID-19

Shanghai Expert Group on Clinical Treatment of New Coronavirus Disease.
Chinese Journal of Infectious Diseases, 2020, 38: Pre-published online. DOI: 10.3760 / cma.j.issn.1000-6680.2020.0016

Abstract
With the deepening of the understanding of corona virus disease 2019 (COVID-19), the Shanghai COVID-19 Clinical Treatment Expert Group followed the National COVID-19 Diagnosis and Treatment Program, and fully absorbed the experience of domestic and foreign peers in the treatment, and continuously optimized and refined the treatment protocol. This expert consensus was formed from the three aspects of etiology and epidemiological characteristics, clinical characteristics and diagnosis, and treatment protocol.

Cite this article: Shanghai Expert Group on Clinical Treatment of New Coronavirus Diseases. Expert Consensus on Comprehensive Treatment of Coronavirus Diseases in Shanghai in 2019 [J / OL]. Chinese Journal of Infectious Diseases, 2020,38 (2020-03-01). rs.yiigle.com/yufabiao/1183266.htm. DOI: 10.3760 / cma.j.issn.1000-6680.2020.0016. [Pre-published online].

Corona virus disease 2019 (COVID-19) was first reported in Wuhan, Hubei Province on December 31, 2019 [1,2]. COVID-19, as a respiratory infectious disease, has been included by the Law of the People’s Republic of China on the Prevention and Control of Infectious Diseases in the Class B infectious diseases stipulated and managed as a Class A infectious disease.
With the deepening of understanding of the disease, China has accumulated some experience in the prevention and control of COVID-19. The Shanghai COVID-19 Clinical Treatment Expert Team follows the National COVID-19 Diagnosis and Treatment Program [3], and fully absorbs domestic and foreign colleagues’ experience in the management of this disease, to improve the success rate of clinical treatment and reduce the patient’s mortality rate, to prevent the progress of the disease, and gradually reduce the proportion of severe cases and improves their clinical prognosis. Based on the continuous optimization and refinement of the treatment protocol, expert consensus has been formed on the relevant clinical diagnosis and treatment.

I. Etiology and epidemiological characteristics
2019 novel coronavirus (2019-nCoV) is a new coronavirus belonging to the genus β. On February 11, 2020, the International Committee on Taxonomy of Viruses (ICTV) named the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [ 4]. Patients with COVID-19 and asymptomatic infection can transmit 2019-nCoV. Respiratory droplet transmission is the main route of transmission, and the virus can also be transmitted through contact. There is a risk of aerosol transmission in confined enclosed spaces. 2019-nCoV can be detected in patients’ stool, urine, and blood. Some patients can be tested positive for fecal pathogenic nucleic acid after the pathogenic nucleic acid test of respiratory specimens is negative. The whole population is generally susceptible. Children, infants, and young children also develop disease, but the condition is relatively mild.

II. Clinical characteristics and diagnosis
(A) clinical characteristics
The incubation period is 1 to 14 d, mostly 3 to 7 d, with an average of 6.4 d. Main symptoms are fever, fatigue, and dry cough. Symptoms can include runny nose, sore throat, chest tightness, vomiting and diarrhea. Some patients have mild symptoms, and a small portion of patients has no symptoms or no pneumonia.
The elderly and those suffering from basic diseases such as diabetes, hypertension, coronary atherosclerotic heart disease, and extreme obesity tend to develop severe illness after infection. Some patients develop symptoms such as dyspnea within 1 week after the onset of the disease. In severe cases, they can progress to acute respiratory distress syndrome (ARDS) and multiple organ dysfunction. The time to progression to severe illness was approximately 8.5 days. It is worth noting that in the course of severe and critically ill patients, there may be moderate to low fever, even without obvious fever. Most patients have a good prognosis, and deaths are more common in the elderly and those with chronic underlying disease.
The early CT examination showed multiple small patches or ground glass shadows, and the internal texture of the CT scans was thickened in the form of grid cables, which was obvious in the outer lung zone. A few days later, the lesions increased and the scope expanded, showing extensive lungs, multiple ground glass shadows, or infiltrating lesions, some of which showed consolidation of the lungs, often with bronchial inflation signs, and pleural effusions were rare. A small number of patients progressed rapidly, with imaging changes reaching a peak on days 7 to 10 of the course. Typical “white lung” is rare. After entering the recovery period, the lesions are reduced, the scope is narrowed, the exudative lesions are absorbed, part of the fiber cable shadow appears, and some patients’ lesions can be completely absorbed.
In the early stage of the disease, the total number of white blood cells in the peripheral blood was normal or decreased, and the lymphocyte count was reduced. Some patients may have abnormal liver function, and the levels of lactate dehydrogenase, muscle enzyme, and myoglobin may increase; troponin levels may be increased. Most patients had elevated CRP and ESR levels and normal procalcitonin levels. In severe cases, D-dimer levels are elevated, other coagulation indicators are abnormal, lactic acid levels are elevated, peripheral blood lymphocytes and CD4 + T lymphocytes are progressively reduced, and electrolyte disorders and acid-base imbalances are often caused by metabolic alkalosis. Elevated levels of inflammatory cytokines (such as IL-6, IL-8, etc.) can occur during the disease progression stage [5].
(B) diagnostic criteria
1. Suspected cases:
Combined with the following epidemiological history and clinical analysis. Suspected cases were diagnosed as having any one of epidemiological history and meeting any two of the clinical manifestations, or having no clear epidemiological history but meeting three of the clinical manifestations. ① Epidemiological history: Travel history or residence history of Wuhan and surrounding areas or other communities with case reports within 14 days before the onset; history of contact with 2019-nCoV infected person(s) (positive nucleic acid test) within 14 days before the onset ; Patients with fever or respiratory symptoms from Wuhan and surrounding areas or from communities with case reports within 14 days before the onset of the disease; or cluster onset. ② Clinical manifestations: fever and / or respiratory symptoms; with the above-mentioned imaging features of the new coronavirus pneumonia; the total number of white blood cells was normal or decreased in the early stage of onset, and the lymphocyte count decreased.
2. Confirmed cases:
A confirmed case is diagnosed with one of the following pathogenic evidence. ① Real-time fluorescent reverse transcription PCR detected 2019-nCoV nucleic acid positive. ② Viral gene sequencing revealed high homology with the known 2019-nCoV. ③ Besides nasopharyngeal swabs, it is recommended to take as much sputum as possible. Lower respiratory tract secretions can be collected for viral nucleic acid testing in patients undergoing tracheal intubation.
(C) Differential diagnosis
It is important to distinguished COVID-19 diagnosis from other known viral pneumonias such as influenza virus, parainfluenza virus, adenovirus, respiratory syncytial virus, rhinovirus, human metapneumovirus, severe acute respiratory syndrome (SARS) coronavirus, etc. , and from Mycoplasma pneumoniae, Chlamydia pneumonia and bacterial pneumonia. In addition, it should be distinguished from non-infectious diseases, such as pulmonary interstitial lesions and organizing pneumonia caused by connective tissue diseases such as vasculitis and dermatomyositis [6,7].
(D) clinical classification
1. Mild type:
The clinical symptoms were mild, and no pneumonia manifested on imaging examination.

2. Moderate (common) type:
With fever, respiratory tract and other symptoms, imaging examination showed pneumonia.

Early warning of severe cases progressed from moderate (common) type patients should be strengthened. Based on current clinical studies, early warning indicators of progression into severe disease include elderly (age> 65 years) with underlying diseases, CD4 + T lymphocyte count 50%on in lung imaging for 2 to 3 consecutive days, lactic dehydrogenase (LDH)> 2 times the upper limit of normal value, blood lactic acid ≥ 3 mmol / L, and metabolic alkalosis [8].
3． Severe type:
Meet any of the following. ① Shortness of breath, respiratory rate ≥ 30 times / min; ② In resting state, arterial oxygen saturation (SaO2) ≤ 93%; ③ arterial partial pressure of oxygen, PaO2) / fraction of inspired oxygen (FiO2) ≤300 mmHg (1 mmHg = 0.133 kPa). At high altitudes (above 1 000 m), PaO2 / FiO2 should be corrected according to the following formula: PaO2 / FiO2 × [Atmospheric Pressure (mmHg) / 760].
Pulmonary imaging showing lesions progressed significantly within 24 to 48 hours, and those with more than 50% of the lesions were managed as severe.
4． Critical type:
Those who meet any of the following can be judged as critical. ①Respiratory failure occurs and requires mechanical ventilation; ②Shock occurs; ③Combination with other organ failure requiring ICU monitoring and treatment.

(E) Clinical monitoring
The patient’s clinical manifestations, vital signs, fluid volume, gastrointestinal function and mental state are monitored daily.
All patients were dynamically monitored for terminal blood oxygen saturation. For severe and critical patients, timely blood gas analysis is performed according to the changes of the patient’s condition; blood routine, electrolytes, CRP, procalcitonin, LDH, blood coagulation function indicators, blood lactic acid, etc. are tested at least once every 2 days; liver function, kidney function , ESR, IL-6, IL-8, lymphocyte subsets, at least once every 3 days; chest imaging examination, usually every 2 days. For patients with ARDS, routine ultrasound examination of the heart and lungs at the bedside is recommended to observe extravascular lung water and cardiac parameters. For monitoring of extracorporeal membrane oxygenation (ECMO) patients, refer to the implementation section of ECMO.

III. Treatment plans
(A) antiviral treatment
Recommend experimental use of hydroxychloroquine sulfate or chloroquine phosphate, or abidol for oral administration, interferon atomization and inhalation, interferon κ is preferred. It is not recommended to use 3 or more antivirals at the same time. The antiviral treatment should be stopped immediately after viral nucleic acid becomes negative. The efficacy of all antiviral drugs remains to be evaluated in further clinical studies.
For severe and critical patients with viral nucleic acid positive, plasma from recovered patients can be used. For detailed operation and management of adverse reactions, please refer to the “Clinical Treatment Protocol for COVID-19 using Plasma from COVID-19 Patients in Recovery Period” (trial version 1) [3]. Infusion within 14 days of the disease onset may be more effective. If the viral nucleic acid is continuously detected positive at the later stage of the disease, the plasma treatment can also be used.
(B) treatment for mild and moderate types
Recommend enhanced supportive treatment to ensure sufficient heat; maintenance of water and electrolyte balance for internal environment stability; close monitoring of patient vital signs and finger oxygen saturation. Give effective oxygen therapy in time. Antibacterials and glucocorticoids are not recommended in principle. The patient’s condition needs to be closely monitored. If the disease progresses significantly and there is a risk of progressing into severe disease, it is recommended to take comprehensive measures to prevent the disease from progressing to severe. Low-dose short-course glucocorticoids can be used with caution (see the application section of glucocorticoids for specific protocols). Heparin anticoagulation and high-dose vitamin C treatment are recommended [9,10]. Low-molecular-weight heparin 1 to 2 dose per day, continued until the patient’s D-dimer level returned to normal. Once fibrinogen degradation product (FDP) ≥10 µg / mL and / or D-dimer ≥5 μg / mL, switch to unfractionated heparin. Vitamin C is administered at a dose of 50 to 100 mg / kg per day, and should be continued until significant improvement in the oxygenation index. If lung lesions progress, it is recommended to apply large doses of broad-spectrum protease inhibitors from 600 to 1 million units / day until the pulmonary imaging examination improves. In case of “cytokine storm”, intermittent short veno-venuous hemofiltration (ISVVH) is recommended [11].
(C) Organ function supportive treatment for severe and critically ill patients
1. Protection and maintenance of cyclic functions:
Implement the principle of early active controlled fluid replacement. It is recommended to evaluate the effective volume and initiate fluid therapy as soon as possible after admission. Severe patients can choose intravenous or transcolonic fluid resuscitation depending on the conditions. The preferred supplement is lactated Ringer’s solution. Regarding vasoactive drugs, noradrenaline and dopamine are recommended to maintain vascular tone and increase cardiac output. For patients with shock, norepinephrine is the first choice. It is recommended to start low-dose vasoactive drugs at the same time as fluid resuscitation to maintain circulation stability and avoid excessive fluid infusion. Cardioprotective drugs are recommended for severe and critically ill patients, and sedative drugs that inhibit the heart are avoided as much as possible. For patients with sinus bradycardia, isoprenaline can be used. For patients with sinus rhythm, heart rate 300 mmHg, the dose of broad-spectrum protease inhibitor can be reduced to 1 million units / d. Anticoagulation therapy can be used to protect endothelial cells and reduce cytokine release. Anticoagulation with unfractionated heparin (3 to 15 IU / kg per hour) when FDP ≥10 µg / mL and / or D-dimer ≥5 μg / mL . The patient’s coagulation function and platelets must be re-examined 4 h after the first use of heparin. With ISVVH, 6 to 10 hours per day.
7. Sedation and Artificial Hibernation:
Patients undergoing mechanical ventilation or receiving ECMO need to be sedated on the basis of analgesia. For patients with severe man-machine confrontation during the establishment of an artificial airway, short-term application of low-dose muscle relaxants is recommended. Hibernation therapy is recommended for severe patients with oxygenation index 8. Oxygen therapy and respiratory support:
① Oxygen therapy with nasal cannula or mask, SaO2 ≤93% under resting air, or SaO2 <90% after exercise, or oxygenation index (PaO2 / FiO2) 200-300 mmHg; with or without respiratory distress. Continuous oxygen therapy is recommended. ② Transnasal high-flow nasal cannula oxygen therapy (HFNC), receiving nasal cannula or mask oxygen therapy for 1 to 2 hours. HFNC is recommended when oxygenation fails to meet treatment requirements, and respiratory distress does not improve; or hypoxemia during treatment and / or exacerbation of respiratory distress; or an oxygenation index of 150 to 200 mmHg. ③ Noninvasive positive pressure ventilation (NPPV) is an option when receiving 1 to 2 h of HFNC oxygenation does not achieve the treatment effect, and there is no improvement in respiratory distress; or hypoxemia and / or exacerbation of respiratory distress during treatment; or When the oxygenation index is 150 ～ 200 mmHg. ④ Invasive mechanical ventilation should be considered when HFNC or NPPV treatment for 1 to 2 hours oxygenation cannot meet the treatment requirements, no improvement in respiratory distress; or hypoxemia and / or exacerbation of respiratory distress during treatment; or oxygenation index 9. ECMO implementation:
Those who meet one of the following conditions may be considered implementing ECMO. ① PaO2 / FiO2 60 mmHg for more than 6 h. ECMO mode is preferred for intravenous-venous ECMO.

(D) Some Specific issues and managements
1. Application of glucocorticoids:
Use glucocorticoids with caution. Glucocorticoids can be added with imaging shows significant progress in pneumonia; SaO2 ≤ 93% or shortness of breath (respiratory frequency ≥ 30 breaths / min) or oxygenation index ≤ 300 mmHg in the state of no oxygen inhalation, especially when the disease progresses significantly faster and there is a risk for intubation. It is recommended to promptly withdraw glucocorticoid when intubation or ECMO support can maintain effective blood oxygen concentrations. For non-severe patients, it is recommended to use methylprednisolone at 20 to 40 mg / d, and for severe patients at 40 to 80 mg / d, and the course of treatment is generally 3 to 6 days. Can be increased or decreased according to body weight [12].
2. Use of immunomodulatory drugs:
Injecting thymosin subcutaneously twice a week has certain effects on improving patients’ immune function, preventing the disease from becoming worse, and shortening the time of detoxification. Due to the lack of specific antibodies, high-dose intravenous immunoglobulin therapy is currently not supported. However, some patients have low levels of lymphocytes and at the risk of co-infection with other viruses, and in these cases human immunoglobulin can be infused intravenously at 10 g / d for 3 to 5 days.
3． Accurate diagnosis and treatment of bacterial and fungal infections:
Clinical microbiological monitoring should be done to all severe and critical cases. The sputum and urine samples are collected daily for culture. Blood culture should be promptly done in patients with high fever. All patients with suspected sepsis who have indwelling vascular catheters should be sent for peripheral venous blood culture and catheter blood culture at the same time. For patients with suspected sepsis, it may be considered collecting peripheral blood for molecular diagnostic tests for etiology, including PCR-based molecular biology testing and next-generation sequencing.
Elevated procalcitonin levels indicate for the diagnosis of sepsis / septic shock. When COVID-19 progresses, there is an increase in CRP levels, which is not specific for the diagnosis of sepsis caused by bacterial and fungal infection.
Critically ill patients with open airways are often prone to bacterial and fungal infections at a later stage. If sepsis occurs, empirical anti-infective treatment should be given as soon as possible. For patients with septic shock, empirical antibacterial drugs can be used in combination before obtaining an etiological diagnosis, while covering the most common Enterobacteriaceae, Staphylococcus and Enterococcus infections. Patients with infection after hospitalization can choose β-lactamase inhibitor complex. If the treatment effect is not good, or the patient has severe septic shock, it can be replaced with carbapenem drugs. In considering enterococci and staphylococcal infections, glycopeptide drugs (vancomycin) can be added for empirical treatment. Daptomycin can be used for bloodstream infections, and linezolid can be used for lung infections. Attention should be paid to catheter-related infections in critically ill patients, and treatment should be empirically covered with methicillin-resistant staphylococci. Glycopeptide drugs (vancomycin) can be used for empirical treatment. Candida infection is also more common in critically ill patients. Candida should be covered empirically when necessary. Echinocin drugs can be added. With the length of hospitalization of critically ill patients, drug-resistant infections can gradually increased. At this time, the use of antibacterial drugs must be adjusted according to drug sensitivity tests.
4． Nosocomial infection prevention and control:
① According to the Basic System for Infection Prevention and Control of Medical Institutions (Trial) [13] of the China National Health and Health Commission 2019, hospitals should actively implement evidence-based infection prevention and control clustering intervention strategies to effectively prevent ventilator-associated pneumonia and intravascular catheter-related blood flow Infections, urinary tract-associated urinary tract infections, multi-resistant bacteria and fungal infections such as carbapenem-resistant gram-negative bacilli. ② Strictly follow the National Health and Health Commission’s “Technical Guidelines for the Prevention and Control of New Coronavirus Infection in Medical Institutions (First Edition)”, “Guidelines for the Use of Common Medical Protective Products in the Prevention and Control of Pneumonia of New Coronavirus Infection (Trial)” and “New Coronary Pneumonia During the epidemic, the requirements of Technical Guidelines for Protecting Medical Staff (Trial) [14,15,16], hospitals should strengthen process of management, and the correct selection and usage of personal protective equipment such as masks, gowns, protective clothing, eye masks, protective masks, gloves, etc, and implement disinfection and quarantine measure to minimize the risk of nosocomial infections and to eliminate infections in medical staff.
5． Treatment of infants and young children:
Children with mild symptoms are treated with symptomatic oral medicines. For moderate disease type, treatments with Traditional Chinese Medicine (TCM) with syndrome differentiation can be considered in addition to symptomatic oral treatments. If combined with bacterial infection, antibacterial drugs can be added. Severely ill children are mainly under symptomatic and supportive treatments. By experience, Ribavirin injection is given for antiviral therapy empirically at 15 mg / kg (2 times / day). Ribavirin treatment should be limited to no more than 5 days.
(E) Integrated traditional Chinese and western medicine
The combination of traditional Chinese and western medicine for the treatment of new coronavirus pneumonia can improve the synergistic effect. For adult patients, the condition can be improved through TCM syndrome differentiation. For mild disease, those with a syndrome of wind-heat type are given the TCM Yinqiaosan plus and minus treatment; those with gastrointestinal symptoms and those with damp-wetting and yang-type syndrome are given the plus and minus Xuanpuxialing and Sanren decoction. For moderate disease, those with syndromes of hot and evil stagnation of lungs can be treated with Ma Xing Shi Gan Decoction; those with syndromes of dampness and stagnation of lungs can be treated with Da Yuan Yin, Gan Lu Fang Dan, etc. These treatments can control to some degree the progression of the disease, reducing the incidence of progression from moderate to severe type. For anorexia, nausea, bloating, fatigue, anxiety and insomnia, the Xiao Chai Hu Tang plus and minus treatment can significantly improve symptoms. For severe patients, if the fever persists, or with high fever, bloating, and dry stools or constipation, and those who are heat-tolerant and the lungs are closed, Dachengqi Decoction enema can be given to release symptoms, or Baihu Decoction, Shengjiang San and Xuanbai Chengqi Decoction plus and minus can be used to reduce the progression from severe to critical illness.
In children with mild symptoms, the syndrome differentiation belongs to the epidemic offence, Yinqiaosan or Xiangsusan plus and minus treatment can be used. Children with moderate symptoms, those with damp heat and closed lungs, are given Ma Xing Shi Gan Decoction and Sanren Decoction; those with moderate scorching dampness and heat such as bloating and vomiting with abdominal distension can be BuHuanJinzhengqi San plus and minus. For severe children patients with epidemic toxicity closing the lung (currently rare in the country), please refer to adult Xuanbai Chengqi Decoction and Manna Disinfection Danjiao; if the poisonous hot accumulates, the gas can’t pass, and food and medicines are not tolerated, the Rhubarb Decoction is given to enema for emergency.
(F) discharge standards
Those who meet all the following conditions can be considered for discharge: ①The body temperature returns to normal> 3 d; ②Respiratory symptoms have improved significantly; ③Imaging of the lungs shows a significant improvement of acute exudative lesions; ④Two consecutive negative airway nucleic acid tests (sampling time at least 1 d apart); ⑤ After the nucleic acid test of the respiratory specimen is negative, the fecal pathogenic nucleic acid test is also negative; ⑥ The total disease course exceeds 2 weeks.
(G) Self-management of discharged patients
1. For discharged patients, close follow-up is still required. Follow-up is recommended at 2 weeks and at 4 weeks after discharge to the designated follow-up clinic.
2. When a patient is discharged from the hospital, his place of residence and address in the city should be specified.
3． Patients should rest at home for 2 weeks after leaving the hospital, avoid activities in public places, and must wear masks when going out.
4． According to the patient’s address (including hotel), the relevant district health committee is responsible for coordinating the corresponding medical institution for health management. Professionals will visit for the patient’s temperature twice a day for 2 weeks, ask their health status, and deliver related health education.
5． If fever and / or respiratory symptoms recur, the corresponding medical institution shall report to the District Health and Health Commission and the District Centers for Disease Control and Prevention in time, and assist in sending the patient(s) to the designated medical institutions in the area for treatment.
6. After receiving the report, the District Health and Health Committee and the District Centers for Disease Control and Prevention should report to the superior department in a timely manner.
Panelist
Writing experts (sorted in alphabetical order by last name): Wu Yuan (Department of Critical Medicine, Renji Hospital, Shanghai Jiaotong University School of Medicine), Hu Bijie (Department of Infectious Diseases, Zhongshan Hospital, Fudan University), Li Feng (Department of Respiratory Medicine, Shanghai Public Health Clinical Center), Xin Li (Department of Cardiovascular Surgery / ECMO Treatment Center, Zhongshan Hospital Affiliated to Fudan University), Li Yingchuan (Department of Anesthesiology, Sixth People’s Hospital Affiliated to Shanghai Jiaotong University), Lu Hongzhou (Department of Infection and Immunology, Shanghai Public Health Clinical Center), Mao Enqiang (Shanghai Jiaotong University Medicine Department of Emergency Medicine, Ruijin Hospital Affiliated to the Hospital), Qu Hongping (Department of Critical Care Medicine, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine), Shi Kehua (Department of Respiratory Medicine, Shanghai University of Traditional Chinese Medicine Hospital of Shanghai University of Traditional Chinese Medicine), Wang Lan (Department of Pulmonary Circulation, Shanghai Pulmonary Hospital Affiliated to Tongji University ), Wang Qibing (Department of Laboratory Medicine, Zhongshan Hospital Affiliated to Fudan University), Wang Sheng (Department of Emergency Medicine, Tenth People’s Hospital Affiliated to Tongji University), Yu Kanglong (Department of Emergency and Critical Care, First People’s Hospital Affiliated to Shanghai Jiaotong University), Zeng Mei ( Department of Infectious Diseases, Children’s Hospital of Fudan University), Zhang Wei ( Department of Respiratory Diseases, Shuguang Hospital Affiliated to Shanghai University of Chinese Medicine, Zhang Wenhong (Department of Infectious Diseases, Huashan Hospital Affiliated to Fudan University), Zhu Duming (Department of Critical Medicine, Zhongshan Hospital Affiliated to Fudan University), Zhu Lei (Department of Respiratory Medicine, Zhongshan Hospital Affiliated to Fudan University)

Consulting experts (in alphabetical order by last name): Li Qiang (Department of Respiratory Medicine, Oriental Hospital Affiliated to Tongji University), Li Xiangyang (Department of Respiratory Medicine, East China Hospital Affiliated to Fudan University), Qu Jieming (Department of Respiratory Medicine, Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine), Song Yuanlin (Affiliated to Fudan University Department of Respiratory Medicine, Zhongshan Hospital), Tian Rui (Department of Critical Care, First People’s Hospital Affiliated to Shanghai Jiaotong University), Wang Xingpeng (Shanghai Shenkang Hospital Development Center), Wu Yingen (Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine), Xu Jinfu (Affiliated to Tongji University Department of Respiratory Medicine, Shanghai Pulmonary Hospital, Xu Jie (Department of Infectious Diseases, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine), Zhang Huiyong (Department of Pulmonology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine), Zhu Tongyu (Urology, Shanghai Public Health Clinical Center) Zhuchen Chen (Department of Emergency, Huashan Hospital, Fudan University)

Conflict of interest: All authors declare no conflict of interest

参考文献
[1]
武汉市卫生健康委员会.武汉市卫健委关于当前我市肺炎疫情的情况通报[EB/OL].(2020-12-31)[2020-02-25]. http://wjw.wuhan.gov.cn/front/web/showDetail/2019123108989.
[2]
World Health Organization. Naming the coronavirus disease (COVID-2019) and the virus that causes it[EB/OL].[2020-02-25]. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/technical-guidance/naming-the-coronavirus-disease-(covid-2019)-and-the-virus-that-causes-it.
[3]
国家卫生健康委办公厅.新型冠状病毒肺炎诊疗方案（试行第六版）[EB/OL]. （2020-02-18）[2020-02-25]. http://www.nhc.gov.cn/yzygj/s7653p/202002/8334a8326dd94d329df351d7da8aefc2/files/b218cfeb1bc54639af227f922bf6b817.pdf.
[4]
Gorbalenya AE，Baker SC，Baric RS，et al. Severe acute respiratory syndrome-related coronavirus：the species and its viruses-a statement of the Coronavirus Study Group[J/OL].BioRxiv,2020(2020-02-11)[2020-02-25]. https://www.biorxiv.org/content/10.1101/2020.02.07.937862v1.DOI：10.1101/2020.02.07.937862.
[5]
Lu HZ, Ai JW, Shen YZ，et al. A descriptive study of the impact of diseases control and prevention on the epidemics dynamics and clinical features of SARS-CoV-2 outbreak in Shanghai, lessons learned for metropolis epidemics prevention. medRxiv，2020（2020-02-23）[2020-02-25]. https://www.medrxiv.org/content/10.1101/2020.02.19.20025031v1. DOI：10.1101/2020.02.19.2002503.
[6]
Ai JW, Zhang Y, Zhang HC,et al. Era of molecular diagnosis for pathogen identification of unexplained pneumonia, lessons to be learned[J]. Emerg Microbes Infect,2020,In press.
[7]
Ai JW, Zhang HC, Xu T，et al. Optimizing diagnostic strategy for novel coronavirus pneumonia, a multi-center study in Eastern China[J/OL].medRxiv,2020(2020-02-17)[2020-02-25]. https://www.medrxiv.org/content/10.1101/2020.02.13.20022673v1.DOI:10.1101/2020.02.13.20022673.
[8]
Wang D, Hu B, Hu C, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China[J/OL]. JAMA,2020[2020-02-25]. https://jamanetwork.com/journals/jama/fullarticle/2761044.[published online ahead of print February 07, 2020]. DOI:10.1001/jama.2020.1585.
[9]
Chen Y, Ma L, Song X, et al. Beneficial effects of fluid resuscitation via the rectum on hemodynamic disorders and multiple organ injuries in an experimental severe acute pancreatitis model[J]. Pancreatology,2015,15(6):626-634. DOI: 10.1016/j.pan.2015.09.001.
[10]
Ma L, Chen Y, Song X, et al. Vitamin C attenuates hemorrhagic hypotension induced epithelial-dendritic cell transformation in rat intestines by maintaining GSK-3β activity and E-cadherin expression[J]. Shock,2016,45(1):55-64. DOI: 10.1097/SHK.0000000000000486.
[11]
李磊，汤耀卿，毛恩强,等.急性重症胰腺炎血液滤过治疗的机制[J].世界华人消化杂志,2004,12（12）：2822-2825. DOI：10.3969/j.issn.1009-3079.2004.12.012.
[12]
Shang L, Zhao J, Hu Y, et al. On the use of corticosteroids for 2019-nCoV pneumonia[J/OL]. The Lancet, 2020（2020-02-11）[2020-02-25]. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30361-5/fulltext.DOI:10.1016/S0140-6736(20)30361-5.
[13]
国家卫生健康委办公厅.医疗机构感染预防与控制基本制度（试行）[EB/OL].(2019-05-18)[2020-02-25].http://www.nhc.gov.cn/yzygj/s7659/201905/d831719a5ebf450f991ce47baf944829.shtml.
[14]
国家卫生健康委办公厅.医疗机构内新型冠状病毒感染预防与控制技术指南（第一版）[EB/OL].(2020-01-22)[2020-02-25]. http://www.nhc.gov.cn/yzygj/s7659/202001/b91fdab7c304431eb082d67847d27e14.shtml.
[15]
国家卫生健康委办公厅.新型冠状病毒感染的肺炎防控中常见医用防护用品使用范围指引(试行)[EB/OL]. （2020-01-26）[2020-02-25]. http://www.nhc.gov.cn/yzygj/s7659/202001/e71c5de925a64eafbe1ce790debab5c6.shtml.
[16]
国家卫生健康委办公厅.新冠肺炎疫情期间医务人员防护技术指南（试行）[EB/OL].（2020-02-21）[2020-02-25]. http://www.henanyz.com/uploadAttach/20200224/20200224095242_338.pdf.

The original documents in Chinese: https://mp.weixin.qq.com/s/bF2YhJKiOfe1yimBc4XwOA

Translated by Dr. Qi Chen

The following is from Thomas Levy, M.D, J.D., a board certified cardiolosit and a prolific medical writer of 13 books and a international speaker.  Thomas is a good friend of mine and I trust him.  Dr. Frank Shallenberger is also an internationally well known doctor whom I trust as well.  Although I have not personally tested this, I will recommend to you just in case you need it.  This method makes scientific sense and is safe, most definitely worth trying, especially now at this global covid-19 crisis. -Richard Cheng, M.D., Ph.D.

An At-Home Treatment That Can Cure Any Virus, Including Coronavirus

Originally Conceptualized, circa 1990, by Charles Farr, MD
Subsequently Researched and Prescribed by Frank Shallenberger, MD
Current Protocol Created by Thomas Levy, MD, JD

Although COVID-19, aka coronavirus, is deadly in some select cases, and it can spread rapidly, there is a simple, very inexpensive, and highly effective treatment that can treat and rapidly resolve coronavirus and virtually any other respiratory virus. While different individuals can be expected to have variable degrees of positive response, this intervention can be anticipated to eliminate eventual fatal disease outcomes in all but the most advanced cases.

As I hope you will eventually experience, the treatment works for all acute viral infections, and especially well for flu viruses of any variety. In fact, although we are constantly conditioned to not believe in anything “too good to be true,” you will never have to worry about getting a cold or the flu again because you can cure it on your own.

The key ingredient in this treatment is common household 3% hydrogen peroxide, and this is the same substance that can be purchased in a 32-ounce plastic bottle at Walmart, for 88 cents, or at Walgreens for under a $1.00. Perhaps you have never heard of hydrogen peroxide therapy, but since the treatment was first championed by Dr. Charles Farr in about 1990, thousands of doctors have used this therapy for decades to conquer infections in many thousands of patients throughout the world.

How and Why Hydrogen Peroxide Works

Because hydrogen peroxide consists of a water molecule (H2O) with an extra oxygen atom (H2O2), it is this extra oxygen atom that makes it so deadly for viruses. In order to comprehend why H2O2 therapy works so well, you must first understand that viral infections are eradicated from the body not by killing the virus itself, but rather by killing the cells that produce them.

Technically, viruses are not alive, and so it is not possible to kill them. But some agents can physically break down the viral structure and render them inactive. Viruses are actually pieces of genetic code that, in and of themselves, can neither survive nor reproduce. Therefore, in order to replicate, viruses need to infect cells, which means that in the interior of cell, a virus uses the cell’s own DNA and RNA in order to effectively reproduce. Essentially, therefore, the virus controls an infected cell and uses the cell to manufacture new viruses. Then, the new virus can exit the cell and proceed to infect other cells. As a result, the way to control any viral infection is not to kill the virus; rather, the infected cells that have been turned into viral factories must be killed. This is the role of the extra oxygen atom in hydrogen peroxide.

Under normal circumstances with a healthy immune system, one’s immune cells produce their own hydrogen peroxide to kill the infected cells that propagate viruses. When one’s immune cells are overwhelmed, such as the case with COVID-19, hydrogen peroxide therapy merely assists the immune cells in doing the job for which they were originally created.

One Disadvantage of Dr. Farr’s Original H2O2 Therapy

From a patient and consumer perspective, the single main drawback to Dr. Farr’s original therapy is/was that it is primarily an intravenous (IV) therapy. Under most circumstances, this means that you must either administer the IV needle yourself or depend upon another person to assist you. Unfortunately, this is beyond the logistical (and perhaps financial) capacity of most people, and it may be one reason why the original hydrogen peroxide therapy is not more widespread. Nevertheless, it should be realized that the proper intravenous application of hydrogen peroxide exerts a powerful anti-viral and general anti-pathogen effect.

Dr. Shallenberger’s Ingenious Use of a Nebulizer

The great news is that there is a safe and simple way to avoid doctors and IV needles. This method developed by Dr. Frank Shallenberger is almost as effective as IV, can be performed at home, and is much less costly than IV.

The treatment is known as nebulized hydrogen peroxide, and Dr. Shallenberger began using the technique some years ago when he had a patient who was taking asthma medication that her doctor had been administering in a nebulizer. For those who are unfamiliar, a nebulizer is a device that is able to convert a liquid into tiny, microscopic bubbles. As a result, these extremely small bubbles, which appear as smoke escaping from the nebulizer, can be inhaled into the deepest regions of the lungs without any discomfort or irritation. Such a device has long been utilized for asthmatics to get medication to open their lungs, but Shallenberger further noticed that nebulizers have a systemic effect, which is delivery far beyond the lungs only. According to one of Dr. Shallenberger’s patients, the inhalation of her prescribed drug in the nebulizer was “unbelievably strong,” and “affected her entire body.”

What Was Taking Place

It turns out that the tiny bubbles were not only providing medication to the patient’s lungs, but the drug was being delivered to her entire body through her lungs. Based on Dr. Farr’s prior research, Shallenberger reasoned that perhaps H2O2 could be delivered to the entire body with a nebulizer.

Dr. Shallenberger tried the nebulizer delivery system on himself, and he was delighted to discover that the treatment was extremely easy to administer, very comfortable like breathing extremely pure air, and the treatment was in no way irritating. Shallenberger’s first actually ill test subject was his wife who had developed the initial symptoms of flu. She immediately began 10-minute treatments every waking hour, and within 72 hours, (three days), the flu was fully cured. Shallenberger was predictably amazed in that even IV hydrogen peroxide cannot resolve flu in much less time.

Since Mrs. Shallenberger’s rapid recovery, Dr. Shallenberger has treated hundreds of cases of colds, flus, sinusitis, and bronchitis all with the same results. Indeed, Shallenberger has discovered that nebulizer treatments actually have an advantage over the IV therapy. Not only is the hydrogen peroxide disseminated into the entire body through the lungs, it is also going directly to the areas of the body that are most affected by viruses: the sinuses, throat, bronchial tract, and lungs. This is especially important since colds and flu viruses replicate to very high titers in these areas, serving to supply a continuous feed of virus to the rest of the body. Effective hydrogen peroxide nebulization quite literally, “chops the head off of the snake,” and the virus present elsewhere in the body can then readily be mopped up when the new virus influx has been terminated.

It should be kept in mind that hydrogen peroxide kills all pathogens very readily upon contact in an open wound. It should, therefore, be understandable why putting a fine mist of hydrogen peroxide in all the areas of maximal viral replication promptly puts the body on a pathway to rapid healing.
Dr. Levy’s Simple, Inexpensive, and Extremely Effective H2O2 Protocol

Early Onset and Treatment of Virus

Regular off-the shelf 3% hydrogen peroxide can be utilized. Preparations of greater pharmacological purity can be obtained if desired.

For most adults, the 3% concentration can be utilized in the nebulization chamber undiluted. This optimizes the degree and rapidity of anti-viral and anti-pathogen effect.

When a runny nose or slightly sore throat is already present, it is recommended that 10-to 15-minute nebulization sessions be undertaken roughly four times daily or until a symptomatic relief is realized. Many individuals report significant improvement only a few hours after the first one or two treatments. But it would be advisable to persist in these treatments several times daily for at least 24 to 48 hours after you feel everything is completely normal in your sinuses, nose, and throat.

For some, the 3% concentration results in too much stinging/burning in the nose. Such individuals can dilute with water until they find their highest tolerable concentration. Nearly everybody can tolerate a 50/50 combination of the 3% hydrogen peroxide and water. However, still lower concentrations can be utilized with clearly beneficial effect.

Prevention/Maintenance

As it is a completely non-toxic therapy, nebulization can be administered as often as desired. If done on a daily basis at least once, a very positive impact on bowel and gut function will often be realized as killing the chronic pathogen colonization present in most noses and throats stops the 24/7 swallowing of these pathogens and their associated toxins.

If daily prevention is not a practical option, the effectiveness of this treatment is optimized when somebody sneezes in your face or you finally get off of the plane after a trans-Atlantic flight. Don’t wait for initial symptoms. Just nebulize at your first opportunity.

， run down and constantly require recharging or replacement.

Final Note: This fact and protocol sheet does not contain a copyright, and a patent has not been applied for. Therefore, I encourage the reader to disseminate the contents far and wide to as many people as possible. Because you now have a simple, inexpensive, and effective way to conquer virtually all viral infections, you do not have to live in fear of COVID-19 or any other pandemic.

Yours in good health,

Thomas E. Levy, MD, JD
www.PeakEnergy.com

March 18, 2020

Dr. Richard Cheng, M.D., Ph.D. Shanghai

A group of medical doctors, healthcare providers and scientists met today online to discuss the high dose intravenous vitamin C use in the treatment of moderate to severe cases of Covid-19 patients. The key guest is Dr. Enqiang Mao, chief of emergency medicine department at Ruijing Hospital, a major hospital in Shanghai, affiliated with the Jiatong University College of Medicine.  Dr. Mao is a member of the Senior Expert Team at the Shanghai Public Health Center, where all Covid-19 patients have been treated. Dr. Mao also co-authored the Shanghai Expert Panel Consensus for the Treatment of Covid-19 Infection, an official document endorsed by the Shanghai Medical Association and the Shanghai city government.

Dr. Mao has been using large doses of IVC to treat patients with acute pancreatitis, sepsis, surgical wound healing, and other medical conditions for over 10 years. This time around when Covid-19 broke out, he and other experts thought of VC and recommended VC for the treatment of moderate to severe cases of Covid-19 patients. The recommendation was accepted by the Shanghai Expert Team early on.  All Covid-19 patients in the Shanghai area have been treated in Shanghai Public Health Center, there has been a total of 358 Covid-19 patients as of March 17th, 2020.

Dr. Mao stated that his group treated ~50 cases of moderate to severe cases of Covid-19 infection with high dose IVC.  The IVC dosing was around 10,000 mg – 20,000 mg a day for 7-10 days, with 10,000 mg for moderate cases and 20,000 for more severe cases by the pulmonary status (mostly the oxygenation index) and the coagulation status. All patients who received IVC improved and there was no mortality. Compared to the average of 30-day hospital stay for all Covid-19 patients, those patients who received high dose IVC had a hospital stay that‘s about 3-5 days shorter than the overall patients. Dr. Mao discussed one severe case in particular who was deteriorating rapidly.  He gave a bolus of 50,000 mg Vit C IV over a period of 4 hours. They watched the patient’s pulmonary (oxygenation index) status stabilizing and improving in real-time.  There were no side effects reported to all the cases treated with high dose IVC.

Among the experts who attended today‘s video conference were: Dr. Atsuo Yanagisawa, professor of medicine at the Kyorin University, Tokyo Japan and the president of the International Society for Orthomolecular Medicine; Dr. Jun Matsuyama of Japan; Dr. Michael J Gonzalez, professor at University of Puerto Rico Medical Sciences, Dr. Jean Drisko, professor of medicine, and Dr. Qi Chen, professor of pharmacology, both at the Kansas University Medical School,  Dr. Alpha “Berry” Fowler, professor of pulmonary and critical care medicine, Virginia Commonwealth University, Dr. Maurice Beer and Asa Kitfield, both from NutriDrip and the Integrative Medical NY, New York City; Dr. Hong Zhang of Beijing Alps Point Health Technologies, LLC;  William T Penberthy, Ph.D. of Scribe LLC, Florida; Ilyes Baghli, MD, president of the Algerian Society of Nutrition and Orthomolecular Medicine (SANMO); Drs. Mignonne Mary and Charles Mary Jr, both of the Remedy Room, New Orleans; Dr. Selvy Rengasamy, president of SAHAMM, Malaysia. I, Richard Cheng, M.D., Ph.D. of Cheng Integrative Health Center of South Carolina, president of Cheng Health Consulting Services of Shanghai and Senior Adviser to ShenZhen Medical Association and ShenZhen BaoAn Central Hospital, initiated and coordinated this conference. Planned but unable to attend are Dr. Thomas Levy, board-certified cardiologist and world-renowned prolific author of Florida; Dr. Andrew Saul, editor-in-chief of Orthomolecular Medicine News Service, Dr. Hyoongjoo Shin of Daegu Korea and Dr. Federica Spurio of Italy.

Albeit a brief meeting of fewer than 45 minutes due to Dr. Mao‘s limited time availability, the audience thanked Dr. Mao for his time and sharing and wished to keep the communication channel open and also able to talk to other clinicians working at the front line against Covid-19.

In a separate meeting, I had the honor to talk to Dr. Sheng Wang, M.D., Ph.D., Professor of Critical Care Medicine of Shanghai 10th Hospital, Tongji University College of Medicine at Shanghai China, who also served at the Senior Clinical Expert Team of the Shanghai Covid-19 Control and Prevention Team. There are 3 lessons that we learned about this Covid-19 infection, Dr. Wang said:
1. Early and large dose IVC is quite helpful in helping Covid-19 patients. The data is still being finalized and the formal papers will gradually be published.
2. Covid-19 patients appear to have a high rate of hyper-coagulability.  Among the severe cases,  ~40% severe cases showed hyper-coagulability, whereas the number among the mild to moderate cases was 15-20%. Heparin was used among those with coagulation issues.
3. The third very important lesson learned is that the time to wear protective clothing for intubation and other emergency rescue measures. If we wait until a patient develops the full-blown signs for intubation, then get ready to intubate, we’ll lose the precious minutes.  So the treatment team should lower the threshold of intubation, to allow proper time (~15 minutes or so) for the team to gear up.  This critical 15-30 minutes could make a difference in the outcome.

Also, both Drs. Mao and Wang confirmed that there are other medical teams in other parts of the country who were using high dose IVC treating Covid-19 patients.

***

Survey Questionnaire for the Research of Vitamin C in Flu and COVID-19. This is a short survey and won‘t take you more than 2-3 minutes.  This research is initiated by Drs. Qi Chen, Hong Zhang and myself, all Chinese American scientists/doctors.

Thank you.

Whether you take Vit C or not, your participation is important and will greatly help our research.

Click below to begin:

https://www.wjx.cn/m/65273635.aspx

Integrative Medical Management of Diabetes and Other Chronic Diseases

-On Essential Metals, Toxic Metals and Diabetes

Richard Z. Cheng, M.D., Ph.D.

Type 2 diabetes (T2DM) is a worldwide major epidemic, affecting hundreds of millions of people worldwide. The world’s most populous country, China, has an estimated 110 million diabetic patients in 2017, according to a World Health Organization’s 2016 estimate, or about 10% of China’s population[1]. A 2017 US CDC report estimates the number of diabetes in the United States at ~ 10% of the US population, or ~ 30 million diabetic patients.  There are an estimated  ~ 84 million pre-diabetic patients, 1 in every 4 persons in US today. Combined, there are currently more than 100 million people in the United States with diabetes or pre-diabetes. By 2050, the total diabetes population will triple, accounting for one-third of the US population. Without intervention, pre-diabetic patients generally develop clinical diabetes within 5 years [2].

Diabetes is a major epidemic, causing huge health and economic burden to all human beings. Comprehensive management of diabetes is urgent. The comprehensive management of diabetes must be a joint effort among the governments, the business sector, the private sector, and the medical and pharmaceutical industry and consumers. Otherwise, diabetes will bring heavy, unsustainable health and financial burden to individuals, families, society, and governments.

Low-carb/ketogenic diet for diabetes management has been received increasing attention worldwide in the past few years among the general public and some healthcare providers. There are more and more clinical studies on low-carb/ketogenic diet demonstrating its effectiveness and utility for the treatment of diabetes, which is the first and foremost step in the treatment of diabetes. The clinical application of low-carb/ketogenic diet for the treatment of diabetes is most definitely a milestone towards the ideal diabetic management, but we shouldn’t stop at low carb/ketogenic diet alone. Those who expect the low-carb/ketogenic diet to be a panacea that can solve all the problems of diabetes may be disappointed down the road.

Like most other chronic diseases, T2DM is also a disease of multiple causes including a variety of exogenous factors (diabetogens), such as excessive sugar in the diet, toxic metals overload, environmental chemical toxins, etc., plus unhealthy lifestyle habits (poor sleep hygiene, stress, lack of exercise, unhealthy diet and poor nutrition). Working together, these extrinsic and intrinsic factors, if without prompt and proper intervention, will lead to a series of metabolic disturbances and wreak havoc to our health.

This is the first of a series of articles attempting to systematically analyze various factors implicated in diabetes including a final Integrative Medical Intervention Proposal for the prevention and treatment of T2DM.

Environmental pollution (metal and  chemical pollutants) and T2DM

Proper functioning of human body requires some metals [3]. Some metals (such as magnesium) exist in large amounts and are called macro nutrients [4]. Macro nutrients are nutrients that require at least 100 mg of each in the daily diet [5]. In contrast, some metals such as copper (Cu), zinc (Zn), iron (Fe) and manganese (Mn), chromium (Cr), etc. exist normally in less than 100 parts per million (ppm), so they are properly called trace elements or micro nutrients [6]. Various metals such as magnesium, zinc, chromium, iron, manganese, and copper are considered essential for normal human health [3,7]. Metals are involved in various physiological processes, such as the repair groups of many proteins, water balance, and cofactors of various enzymes, etc. [8]. Several metals are used as metalloproteinases/metalloenzymes as part of proteins/enzymes [9]. Such metal-free repair group proteins cannot perform their physiological functions [10]. Normalizing the content of various metals in the body is a prerequisite for its normal function [11]. Metals contract or relax muscles and transmit impulses through nerves. Most metals exist as soluble salts that regulate the composition of biological fluids. The proper metabolic function of trace elements depends on their normal levels in various body tissues [12]. Drs. Khan and Awan has an excellent review article on this topic [7].

However, the worldwide industrial and agricultural revolutions over the past century and rapid economic development, especially in China over the past three to four decades, have also brought environmental pollution, including various toxic metals and chemicals. These environmental toxins contaminate our food, water, air, and everything we come into contact with in our daily lives. They are an important cause of chronic diseases today. For everyone, especially healthcare professionals, identifying, testing, and taking steps to prevent these toxins from getting into our body, remove them from our body, or to reduce their impact on our health is critical.

Essential metals and their physiological effects

A growing body of evidence exists and shows that these metals are essential for maintaining normal human physiology. These metal imbalances are closely related to diabetes and its complications. If the imbalance of these metals is not corrected, diabetes and other chronic diseases will ensue. 

Iron (Fe): Ferritin is the major storage form of iron. Ferritin is often higher in patients with diabetes and other chronic diseases, suggesting excess iron load. Serum ferritin levels may be a surrogate marker to predict the development of diabetes. 

Iron is an important metal essential for the synthesis of hemoglobin and myoglobin. Iron, like zinc and vitamin C, is also required for the synthesis of elastin and collagen [13]. In the blood, a small portion of serum iron is transported into cells by glycoproteins (called transferrin) [14]. Ferritin is a way of storing free iron in human tissues. Ferritin levels are often increased in newly diagnosed diabetic patients [15,16]. Compared with non-diabetics, patients with diabetes have higher ferritin levels. Recently, it has been reported that the higher the serum ferritin, the more iron deposition in the tissue, which increases linearly with the duration of diabetes [17]. Elevated serum ferritin is considered an indicator of iron overload and can cause hemochromatosis in severe cases [18]. Multiple studies have shown an association between hemochromatosis and type 2 diabetes [19–21]. High iron levels are a major contributor of intracellular oxidative stress, oxidize various biomolecules, such as nucleic acids, proteins, and lipids, which may promote the development of T2DM by reducing insulin secretion from pancreatic beta cells and increasing insulin resistance [22–26]. Studies have shown a strong relationship between serum ferritin levels and insulin resistance in pre-diabetes [27,28]. In addition to elevated glucose, serum ferritin levels may be a surrogate marker of diabetes to predict the onset of disease [29,30].

Magnesium (Mg): Patients with diabetes, gestational diabetes are usually low in magnesium. Magnesium deficiency plays an important role in the development of insulin resistance and diabetes.

Magnesium is one of the most abundant macro nutrients and is essential for proper health. The activity of more than 300 enzymes requires magnesium, and these enzymes have a variety of important physiological functions in the human body [31,32]. Magnesium-containing enzymes are involved in glucose homeostasis, neurotransmission, and DNA and RNA synthesis [33]. Magnesium plays an important role in regulating insulin secretion from β islet cells and improves insulin binding of insulin receptors [34,35]. Magnesium deficiency has been shown to lead to a decrease in insulin-mediated glucose uptake [31,36]. On the other hand, magnesium supplementation can prevent insulin resistance and reduce the development of diabetes [37]. Some studies report that compared with healthy controls, patients with diabetes have lower levels of magnesium in the serum and increased excretion of magnesium in the urine [36]. Studies have shown that oral magnesium supplements can lower blood sugar, blood pressure, and triglycerides [37]. Magnesium deficiency is a major factor in the development and worsening of diabetes. Low magnesium appears to be one of the direct causes of insulin resistance [38].

A large PREVEND study in the Netherlands this year (2019) studied 5,747 subjects who were initially non-diabetic. After 11 years of follow-up, authors concluded that low plasma magnesium levels were independently associated with a higher risk of diabetes in women [39]. A recent study involving 14,353 participants with a follow-up of over a 29-year showed that extremely low serum magnesium concentrations in American adults were significantly associated with an increased risk of all-cause mortality [40]. Long-term magnesium deficiency significantly promotes insulin resistance, and continuous magnesium supplementation significantly increases serum and intracellular magnesium concentrations. Magnesium supplementation appears to improve insulin-mediated cellular glucose uptake and improve insulin resistance [41–44]. A 10-year study of 13,525 Japanese showed that high magnesium intake reduces the risk of diabetes [45]. After a 28-year comprehensive analysis of more than 200,000 people in 3 cohorts, researchers showed that higher magnesium intake reduces the risk of diabetes, especially when combined with a low-carb diet [46 ].

In patients with diabetes, high magnesium intake and high serum magnesium reduce the risk of coronary heart disease [47]. In animal studies, magnesium seems to not only reduce insulin resistance, but also increase insulin receptors and glucose transporters, which are hallmarks of diabetes [48–50]. In many diabetic patients, there is a vicious cycle of low magnesium leading to insulin resistance and insulin resistance leading to magnesium deficiency [34,51]. A double-blind randomized trial showed that magnesium has been shown to improve the ability of β-cells to secrete insulin as needed in non-diabetic populations [52]. Low magnesium levels can inhibit insulin secretion in non-diabetics [53]. Diabetics with low magnesium levels tend to develop faster and have more complications [54].

Women with gestational diabetes also show low magnesium compared to normal or non-pregnant women [55]. Magnesium and vitamin E supplementation can significantly improve glycemic control and lipid levels in women with gestational diabetes [56].

Manganese (Mn)

Manganese acts as a cofactor in a variety of enzymes, including those related to bone marrow production and the metabolism of carbohydrates, proteins and fats [57]. This is essential for the proper use of choline, thiamine, biotin, vitamin C and vitamin E. Manganese as an enzyme cofactor is also involved in mitochondrial glycoprotein synthesis [58]. When deficient in manganese, the activity of these enzymes is impaired, leading to abnormal cartilage production [59]. Manganese is also a cofactor for pyruvate carboxylase, which plays a role in converting various non-carbohydrates to glucose through gluconeogenesis. In short, manganese is required for normal insulin synthesis, its secretion and manganese imbalance is implicated in the development of diabetes [3]. A study by Forte et al. found a manganese deficiency in patients with type 2 diabetes [60].

Copper (Cu)

Copper is another essential mineral that has multiple biological functions. It is required for the catalytic activity of superoxide dismutase (SOD), and it is involved in protecting cells from superoxide radicals [61]. Copper imbalance is associated with disruption of normal high-density lipoprotein (HDL) and low-density lipoprotein (LDL) balances [62]. Copper also activates the cytochrome oxidase involved in the mitochondrial electron transport chain [63]. In the absence of copper, cytochrome oxidase reduces its activity, which may cause mitochondrial deformation in metabolically active tissues (such as pancreatic acinar cells, liver cells, etc.) [64,65] Existing studies have shown that copper deficiency is one of the causes of the development of cardiovascular disease [66]. Other reports suggest that copper also helps prevent arthritis-related inflammation and epilepsy [67]. Disturbances in copper levels are associated with abnormalities related to the metabolic pathways of diabetes and its complications [3,68]. Copper and zinc metals play a role in protecting human tissues from oxidative damage [69,70].

Zinc (Zn)

Zinc is an essential trace element and is involved in multiple biochemical pathways such as transcription, translation, cell division, and apoptosis [71]. More than 300 enzymes require zinc for their catalytic activity. Removal of zinc from the catalytic site results in the loss of various enzyme activities [72]. About 70% of zinc binds to albumin, and any pathological changes in albumin will affect zinc levels in serum [73]. Zinc malabsorption can cause various types of diseases, including skin, gastrointestinal, neurological, and immune disorders [74].

Chromium (Cr)

The biological activity of chromium depends on its valence and the chemical complexes it forms [12,75]. The trivalent form of chromium has high biological activity and is required for optimal glucose uptake by cells [75,76]. Chromium regulates insulin and blood glucose levels by upregulating glucose transporter (GLUT4) transport in muscle cells to stimulate insulin signaling pathways and metabolism [77]. Chromium deficiency can lead to elevated blood sugar levels and, if persisted for long periods, can lead to the development of diabetes [78]. Some reports suggest that chromium supplements can lower blood sugar levels in patients with diabetes [79]. Prolonged hyperglycemia increases urinary excretion of chromium [3,60].

The relationship between toxic metals and health, chronic diseases, and especially diabetes

When lead, arsenic, zinc, cadmium, mercury and nickel exceed the normal levels, they are powerful oxidants, which can promote the development of chronic diseases including diabetes and even cancer [80].

The toxic metals lead (Pb), nickel (Ni), cadmium (Cd), and arsenic (As) enter the body and deposit in the tissue and are not degradable. As a result, these metals often remain in the tissues for long periods of time, and the problems they cause are often difficult to eliminate. Human tissues can tolerate a certain level of metals. Exceeding this threshold limit can cause tissue damage due to metal toxicity. Some toxic metals, including nickel and arsenic, have been shown to be carcinogens [81–83].

Lead (Pb)

Some toxic metals (including lead) in biological samples (ie, plasma and urine) of diabetic individuals are reported to be higher than non-diabetic individuals [84]. Lead is harmful to most organs of the human body and interferes with metabolism and cellular function [85]. Studies have shown a linear relationship between blood lead levels and renal insufficiency in age-related diseases. This may be due to frequent exposure to environmental lead [86]. Studies have shown that exposure to lead can severely affect the antioxidant pathway [83]. Existing evidence suggests that metal-induced toxicity may cause disturbances in the antioxidant mechanisms in living tissues. As a result, reactive oxygen species (ROS) are produced. This imbalance of antioxidants can lead to peroxidative degradation of proteins, nucleic acids and lipids. The oxidative attack of ROS on cellular components has been implicated in the pathogenesis of several human diseases, including diabetes [87,88]. In fact, most, if not all, chronic diseases are associated with elevated oxidative stress.

Cadmium (Cd)

Cadmium is a heavy metal that is widely found in air, water, and soil. The increase in cadmium in water is absorbed by plants, animals and humans [84]. Regular exposure to cadmium can lead to its excessive accumulation in the kidneys, leading to kidney damage and kidney diseases [87]. In addition, high levels of cadmium can reduce calcium absorption, and severely cause bone and kidney damage, known as “Itai-Itai Disease” (Itai is Japanese for Painful) , caused by widespread cadmium poisoning was first discovered in Japan [89]. It has also been reported that cadmium may down-regulate glucose transporter 4 (GLUT4) transport through insulin and enhance the induction of pancreatic β-cell destruction in diabetes [80].

Arsenic (As)

Arsenic is a naturally occurring lethal metalloid, mainly used in copper alloys and lead batteries. It is also commonly found in the production of pesticides, herbicides and pesticides. Arsenic is a Group I carcinogen by WHO [80,90–92]. The underground water pollution of arsenic is seriously threatening human beings worldwide [81,84,93]. Arsenic is widely recognized as a carcinogen and a strong oxidant that can damage neurons, liver, cardiovascular, subcutaneous and renal organ systems. Chronic arsenic overdose is the most common epidemic in the world, as is diabetes [94].

Regular exposure to arsenic has been linked to a variety of diseases, including certain types of cancer and diabetes. Studies have shown that glucose metabolism is disrupted due to changes in cell signal transduction, and subsequent translocation of GLUT4 to the membrane may be arrested. Some studies have shown that arsenic is associated with β-cell dysfunction [14,75].

Arsenic is mainly found in underground mineral compounds. It is especially common in the Himalayas. In Bangladesh, with a population of 167 million, more than 100 million people suffer from acute arsenic poisoning, accounting for 2 of every 3 people in this Southeast Asian country! As a result of mining and coal burning, arsenic is released into the atmosphere and surface water on which we live, polluting our living environment. Arsenic, lead, mercury and cadmium accumulate in rice. But arsenic is particularly problematic in rice because arsenic is present in water and soil all over the world, and rice grows in water for a long time. Rice contains vitamins, minerals, and carbohydrates, but rice also has something nasty: pollution of metals, especially inorganic arsenic (arsenic). Rice is a major source of inorganic arsenic contamination in the human diet [93]. Rice absorbs 10-20 times more arsenic than other crops. The arsenic content is highest in rice husks, so brown rice has a higher arsenic content [93]. In the past few decades, China’s rapid economic development has also paid a huge price: environmental pollution, especially cadmium, arsenic, lead, and antimony [95].

65% of Chinese people eat rice as their staple food. Of the causes of arsenic excess in Chinese, 60% are thought to be related to arsenic contamination in rice [93]. Half of the world’s population eats rice every day.

About 4% of the 300 million people in the United States have arsenic in public drinking water that exceeds the US Environmental Protection Agency’s (EPA) standard (10ug/L) [96]. The actual number may be well over 4%, as there are many (close to half) water sources in the United States that have not been tested. Globally, it is estimated that superficial groundwater affecting 400 million people has high levels of inorganic arsenic [94]. Seafood, rice, mushrooms, and poultry are the main sources of arsenic in food.

Nickel (Ni)

Nickel is a ferromagnetic element and is mainly used in Ni-Cd batteries. Most people are exposed to nickel in different ways, such as drinking water, air, and eating foods contaminated with nickel [97]. The kidney has been observed to be the main organ of nickel accumulation and therefore the cause of renal insufficiency [98]. Forte et al. found that the nickel content in the blood of patients with type 2 diabetes was significantly higher than that in the normal control group [60].

In short, the researchers analyzed various biological fluids such as serum/plasma, hair, urine, etc. in order to understand changes in metal metabolism in various diseases including diabetes. Among these biological samples, urine is unique because it is easily accessible and non-invasively sampled. In some previously published studies, researchers have shown that the amount of metal in urine corresponds to the amount of metal in their serum [1,14]. Previous studies have shown a link between toxic metals and essential trace metals [78].

References:

Low Carb/Ketogenic Diet has been very hot in the last few years.  Here I share my experiences with Low Carb/Ketogenic diet for myself and a large number of patients for the 4 or 5 years. 

There are 3 reasons why I recommend Low Carb/Ketogenic Diet:

1. Reduce carbohydrate and glucose intake. Low carb/KD is used for the management of metabolic diseases such as T2DM. This is very intuitive and is what most scholars, allied healthcare providers, patients and the general public recognize and are talking about. But even this straightforward appliction of KD (Diabetics have high blood sugar, and low-carbon/ketogenic diet will lower blood sugar level) is still controversial and has not been recognized and accepted by most doctors.

2. Reduce pollution caused by carbohydrate-rich foods, especially pesticides such as glyphosate, which are mainly in crops with high carbohydrate content. This type of contamination is the main cause of Leaky Gut, or Increased GI Permeability and Dysbiosis (gut bacteria imbalance). The latter is the root cause of many chronic diseases and can be found in nearly all chornic disease patients. This is more obvious in many autoimmune diseases. Most patients with autoimmune diseases have Leaky Gut, dysbiosis, increased oxidative stress, and mitochondrial function impairment. Mangement targeting these deficiencies (leaky gut, anti oxidants, mitochondrial nutrition) including low-carb/ketogenic diet, will often result in disease improvement.  In fact, if you ask and check carefully, you will find that most patients with chronic diseases will have gastrointestinal problems. “Let food by thy medicine and medicine be thy food”, our ancestors have long recognized this relationship.  Today this problem is even more obvious: due to the deterioration of our food quality and ever increasing pollution and contaminants.  One can‘t be too careful about the food they eat.

3. Reduce the body’s dependence on glucose as the fuel supply, restore/promote body’s fat as energy supply. Under normal circumstances, we should use both glucose and fat as our fuels.  The two mechanisms for the human body to release and burn glucose and fat as fuel should be efficient and effective. However, due to the excessive amount of calories in todya‘s processed foods, especially the excessive consumption of carbohydrates (glucose and fructose), the demand for our body to release and burn fat as energy is greatly reduced. Our body is supposed to store and release energy on a regular basis.  But due to the excess calories that many people eat today, there is no need for these peoople to release their stored energy (fat).  If they keep doing this for a prolonoged period of time, their body wil forget how to release and burn fat.  Biologically this is called down-regulation of receptors and hormones important in fat metabolism.  Think about this: a typical T2DM patient is overweight (his/her body has lots of fat stored).  But when this diabetic patient misses a meal, s/he may develop low blood sugar, with hypoglycemic symptoms (such as headaches, fatigue, etc). Why? Because his/her body has been relying on sugar as energy for way too long and forgot how to utilized the vast energy source (fat).  This is the root cause of the onset of diabetes, obesity, and many metabolic diseases. 

Therefore, Low Carb/Ketogenic Diet is the FUNDAMENTAL part of my approach to the management and prevention of diseases,  along with other anti-aging/functional medicine principles. For Anti-Aging/Functional Medicine, see my articles elsewhere on this blog.

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