FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, July 5 2023

How to Prevent Sepsis Mortality: Part 2

by Max Langen and Dr. med. Petra Wiechel

To read part 1, click here

OMNS (July 5, 2023) The peer-reviewed scientific literature clearly suggests that global sepsis mortality could be reduced drastically and millions of premature deaths could be prevented. Patients should receive appropriate treatment with standard care, in combination with coenzyme Q10, melatonin, very high dose vitamin C, curcumin, nigella sativa seeds, and optimal doses of other essential nutrients discussed below.

Zinc

A low zinc status is common, affecting 33% of the global population. [1] For a variety of reasons dietary zinc may be insufficient, and zinc absorption in the gut may be inadequate especially in older individuals. Supplementation of zinc can reduce the incidence of infections because zinc is important for the immune system. [2] A recent study with individuals >55 years and a slightly inadequate zinc status showed that supplementation of zinc resulted in a 60% reduction in the incidence of infections and prescriptions of antibiotics. [3] Administration of a zinc nasal spray may also prevent infections by more than 30%, even in people unlikely to be deficient in zinc. [4]

Supplements of zinc reduced the risk of disease progression and mortality by 57% in patients who suffered from severe pneumonia. [5] A study of Covid-19 patients found that zinc treatment reduced the risk of death by 43%. [6] Also, a double-blind RCT showed that twice daily treatment with zinc (25 mg) reduced the risk of admission to the intensive care unit by more than 50%, and reduced the length of the hospital stay. [7]

The antiviral, antibacterial and anti-inflammatory effects of zinc may help prevent and treat infections, and improve and accelerate recovery. Further, by preventing the inflammatory cascade and disease progression, zinc treatment may prevent sepsis. This suggests that, patients at risk of sepsis, especially those with a lower zinc status, should receive zinc treatment.

Evidence shows that zinc treatment (zinc sulfate monohydrate at a dose of 3 mg/kg twice a day orally for 10 d along with standard antibiotics) can significantly reduce mortality by ~ 50% in neonatal sepsis patients. [8,9] A more recent study showed that in children under five years, zinc treatment (≥ 10 mg/d) reduced the risk of mortality from diarrhea, pneumonia, infections and sepsis by 15%, 30%, 44% and 57%. All cause mortality was also cut in half, both in normal weight infants and low birth weight infants. [10]

Zinc treatment would likely also be effective in adult sepsis. Of course, prevention is always better than treatment. Early treatment of infections with zinc will likely help prevent the development of sepsis.

The effectiveness of zinc may be further increased by co-administration of zinc-ionophores which help increase the intracellular levels of zinc (such as quercetin, quinine/quina, or green tea extract and its main compound EGCG). [11,12] For example, studies have shown that robust consumption of green tea reduces the risk of infectious disease. Influenza or Covid-19 infections were reduced by 40% by frequent consumption of green tea. [13,14] Supplementation of the polyphenol quercetin (as quercetin phytosome for improved bioavailability) significantly accelerated viral clearance and reduced the time to recovery in patients with a viral infection. [15] It is likely that at least some of the effects of these substances are due to their consumption leading to increased intracellular zinc levels.

N-Acetylcysteine (NAC) and Glycine

Glutathione is one of the most important antioxidants that helps to prevent many serious conditions and infections by inhibiting oxidative stress and inflammatory processes. However, glutathione levels are low in many individuals, especially in those older, overweight or chronically sick, predisposing them to complications of serious infectious disease. [16,17] Glutathione synthesis requires sufficient amounts of the three amino acids cysteine, glycine and glutamine.

Supplementation of NAC is an efficient way to increase cysteine levels and therefore improve glutathione synthesis. A study of older adults showed that long-term supplementation of NAC (600 mg twice daily) reduced symptomatic episodes of respiratory tract infections. While NAC did not protect from influenza infections, it protected from clinically apparent episodes. Only 25% of the virus-infected people in the NAC group developed symptoms typical of a respiratory infection, while 79% of the virus-infected people in the placebo-group developed such symptoms. [18] By increasing glutathione, NAC improved the immune defense of the body and therefore reduced viral-induced sickness, reducing the severity and duration of the remaining influenza-like symptoms. This suggests that NAC supplements can lower the incidence of serious infectious disease complications like pneumonia and sepsis.

The risk of ventilator-associated pneumonia (VAP), one of the leading causes of hospital-acquired sepsis, was reduced (by 42%) by administration of NAC. [19] However, inhalation of NAC may be even more effective. In mechanically ventilated patients who received aerosolized NAC, the incidence of VAP was reduced by 65%. [20] Therefore, NAC is likely effective for the prevention of both community- and hospital-acquired sepsis. Of note, however, it might not be an effective acute therapy for septic patients. [21]

Since glycine is also required for the synthesis of glutathione, the combination of NAC + glycine may be more effective for the improvement of glutathione status than NAC monotherapy. The combination of glycine and NAC has shown to increase lifespan by 24% (in mice), due to enhancement of glutathione levels and mitochondrial health, reduction of oxidative stress and inflammatory processes. [22] Further, a recent study showed that long-term glycine supplementation dramatically reduces the risk of any respiratory infection (viral, bacterial etc.) by reinforcing the extracellular matrix. Many people who follow a "normal" diet do not get a sufficient supply of glycine -- this seems to be one of the most important risk factors for respiratory infections. And by increasing the intake of glycine, many of the annual infections could be prevented. [23] Supplementing with both NAC and glycine may therefore be a very helpful strategy to prevent infections and reduce the incidence of dangerous infectious disease complications like sepsis.

Probiotics

A recent study with mechanically ventilated trauma-patients has shown that prophylactic administration of a probiotic formula, consisting of Lactobacillus acidophilus, Lactobacillus plantarum, Bifidobacterium lactis and Saccharomyces boulardii through the nasogastric tube and spread on the oropharynx reduced the risk of developing VAP by 66% and the risk of developing sepsis by 78%. [24]

Curcumin

Curcumin (an active ingredient of turmeric) is one of nature's best responses to inflammation. Preclinical data indicated that curcumin can strongly inhibit inflammatory processes in sepsis and improve survival by inhibiting sepsis-induced complications in organs. [25] Since curcumin has a low bioavailability, formulations have been developed that substantially improve gastrointestinal absorption.

Recent studies with septic patients showed that nano-curcumin (160 mg via nasogastric tube twice daily) significantly reduced inflammatory markers, oxidative stress, the severity of sepsis and the progression of organ failure, and it improved endothelial function. This allowed the duration of mechanical ventilation and hospital stay to be reduced, suggesting that curcumin can accelerate the recovery time of septic patients. Therefore, highly bioavailable curcumin formulations (like nano-curcumin or curcumin + piperine etc.) may be an effective therapeutic strategy for critically ill sepsis patients. [26,27]

Many other studies show that curcumin can reduce the risk of developing serious infectious disease complication. In a study with Covid-19 patients, early treatment with nano-curcumin completely prevented disease progression and accelerated the recovery. [28] Patients with Covid-19 who received curcumin had an up to 83% lower risk of death. [29,30] Curcumin may even inhibit malaria. Preclinical results showed that treatment with curcumin may eradicate this parasite and significantly reduce the risk of death. [31]

Nigella sativa (black cumin)

Nigella sativa (raw seeds or seed oil in capsules) is highly effective for the prevention, treatment and eradication of viral and bacterial infectious diseases, including hepatitis-C, helicobacter pylori and respiratory infections. Intake of nigella sativa seeds has shown to modulate the immune defense and reduce the risk of severe infections. Patients with common respiratory infections recover significantly faster when given nigella sativa. Consumption of 40mg/kg/d reduced the risk of symptomatic Covid-19 infections by more than 60%. Also, Covid-19 patients who received early treatment with nigella sativa seeds had a 93% lower risk of progressing to a severe case during their illness. Acutely ill hospitalized Covid-19 patients who received nigella sativa seeds, 80 mg/kg/d (+honey) had a 82% lower risk of death and a faster recovery than those who received a placebo, showing that this treatment can effectively stop the inflammatory progression of infectious diseases. [32]

Preclinical results suggested that high dose treatment with thymoquinone (one of the main active compounds of nigella sativa seeds) may reduce mortality in sepsis by 70 to 90%. Therefore, it may be wise to administer this treatment to (hospitalized) septic patients or to those who are at increased risk of sepsis. [33,34]

Safflower Yellow

Safflower yellow is the main active ingredient derived from Carthamus tinctorius L and has been used in traditional medicine for many diseases. Its anti-inflammatory, anticoagulative and antioxidative effects make it a great candidate for the treatment of sepsis. Very sick patients suffering from severe sepsis or septic shock who received standard care + 200 mg of safflower yellow intravenously had a significantly lower risk of death than those who only received standard care. [35]

Xuebijing

Xuebijing is a herbal preparation consisting of: Carthamus tinctorius L., Paeonia lactiflora Pall., Ligusticum chuanxiong Hort., Salvia miltiorrhiza Bge. and Angelica sinensis (Oliv.) Diels. A recent study showed that xuebijing infections can reduce mortality in septic patients. [36] Another recent study confirmed that this treatment significantly reduces the risk of 28-day mortality by 27%. Secondary outcomes showed that ICU- and hospital mortality were significantly reduced as well. [37]

Acupuncture

Acupuncture has also shown to be an effective therapy for sepsis. A new meta-analysis of 17 RCTs indicates that adjuvant acupuncture therapy in addition to standard care can reduce mortality at 28 days by more than 30% compared with standard care alone. Many other parameters, including white blood cell counts and levels of procalcitonin, tumor necrosis factor (TNF)-α, interleukin (IL)-6, lactic acid and intra-abdominal pressure, and CD3+, CD4+ improved as well. [38] The increased survival of septic patients following acupuncture may at least in part be explained by the significant anti-inflammatory effects of this treatment. [39]

Nutrition, fasting, intestinal health, and psychological stress relief

The functionality of the immune system depends on the quality of the diet. Many infections and severe infectious disease could be prevented by an anti-inflammatory diet rich in micronutrients, polyphenols, unsaturated fatty acids, plant protein and fiber. A study showed that people who consume >500 g/d of vegetables and fruits and >10 g/d of nuts have an ~80% lower risk of getting a respiratory infection. [40] Healthcare workers with Covid-19 who followed a mainly plant based diet high in micronutrients had a 70% lower risk of developing moderate or severe Covid-19 symptoms. Individuals consuming diets high in animal protein had a strongly increased risk of a severe case. [41] Furthermore, a study with more than 30,000 adults >45 years showed that a high adherence to the anti-inflammatory mediterranean diet that is rich in plant foods and olive oil was associated with a 25% lower risk of developing sepsis. [42]

One of the mechanisms by which a healthful plant-based diet reduces infections and infectious disease complications is the regulation of intestinal bacteria. A high intake of fiber (vegetables, fruits, nuts, seeds, legumes, whole grains) and polyphenols helps to improve the bacterial composition of the gut. This, in turn, significantly improves the functionality of the immune system. Yet, fiber intake is severely deficient in hundreds of millions of people, strongly predisposing them to severe diseases like sepsis. Those with the highest consumption of fiber, >29 g/day, had a 56 to 59% lower risk of dying from an infectious disease compared with the lowest intake. [43] Similarly, an increase of daily (unsalted) nut consumption of 28 g, especially tree nuts like walnuts, almonds, cashews, hazelnuts, pistachios, was associated with a 75% lower risk of dying from an infectious disease. [44]

While healthy nutrition is extremely important, the frequency of meals should be considered as well. Our bodies are not adapted to modern eating patterns with several meals per day. These eating patterns are disease-promoting and favor the development of metabolic diseases, diabetes, overweight and, even independent from overweight, silent inflammation with slightly increased inflammatory markers like hsCRP. An elevated level of hsCRP in the blood significantly increased the risk of developing sepsis. [45] Time-restricted feeding or intermittent fasting (for example, no food intake for 16 to 18 hours per day, or fasting for 2 days per week without overall caloric restriction) significantly reduced hs/CRP or CRP in the blood. [46,47] Reducing the meal frequency without overall reducing calories helps to decrease chronic inflammation.

Since chronic inflammatory processes are a leading risk factor for many diseases and severe infectious disease, including sepsis, intermittent fasting patterns may significantly help to reduce mortality and sepsis. A recent study showed that people who engage in periodic fasting had a ~40% lower risk of hospitalization or death from a viral infectious disease (Covid-19). [48]

Emotions and thoughts also influence the immune system. The scientific field of psychoneuroimmunology describes how mind/brain, hormones and immune system interact and influence each other. Psychological stress has been found to have a negative and pro-inflammatory effect on the immune system. Increased psychosocial stress is associated with an elevated risk of developing sepsis. [49] Therefore, mental hygiene and relaxation including exercise, visits in nature, meditation, reducing toxic relations, reducing consumption of panic-spreading mainstream media, etc. will result in improved immune health and a lower risk of developing severe infectious disease.

Whether viruses or bacteria that enter our bodies or live inside of us can cause sickness or not critically depends on lifestyle factors such as the supply of micronutrients, diet quality, meal frequency, gut microbiota, stress level, mental hygiene etc. As Dr. Antoine Béchamp said: "The microbe is nothing. The milieu is everything."

What can you do if a relative is in the hospital, has an infection and is at increased risk of developing or has already developed sepsis?

Unfortunately, therapy with truly high dose nutrients and plant extracts is not part of the standard care in many countries --although millions of lives could be saved in this way. There have often been urgent discussions over high-dose nutrient supplements between relatives of a severely sick hospitalized patient who asked for such treatments and responsible healthcare workers who often try to refuse this, because they did not learn this approach in medical school.

However, A case report in the scientific literature describes a severely sick 74 year old Covid-19 patient with acute respiratory distress syndrome in a Michigan hospital who received intravenous vitamin C from her doctors due to a request from her family. This led to greatly improved outcomes and she had a much faster recovery than the average patient. The doctors were so surprised about this result that they published a report about it. [50] She would not have received this treatment if her family not requested it. Maybe showing this report to other healthcare workers can help to convince them.

Of course, most doctors are very good people who only want the best for their patients. But since they did not learn much in medical school about how to treat sepsis by the treatments described above, and since these treatments are not part of standard care, many doctors will refuse requests to administer them. This is a very unfortunate situation -- and threatening someone with legal action is the last step that we should take. But since this is about saving the life of a relative, if nothing else helps in this situation, it might be necessary to follow the advice of Dr. Thomas Levy, who is not only an internist and cardiologist but also an attorney. He recommends that if you have a family member with sepsis in a hospital and want him/her to receive high dose nutrients and plant extracts for which there is evidence of safety and efficacy, you should demand it and "if you are denied this option, make sure the physician understands that immediate legal action to initiate the therapy will ensue, and that the death of your loved one will assure the initiation of a malpractice suit against him/her." [51]

Of course, some medical professionals will argue that the studies are "not large enough" or that "more studies are needed to quantify the effectiveness" etc. The debate about the efficacy will always continue. However, science only progresses slowly and world-wide there are 11 million sepsis deaths every year, which equals more than 30,000 deaths per day. And as Dr. Levy explains, if there is a therapy that has at least some evidence of efficacy (and many of the treatments presented here have more than just some evidence), and which is cheap and usually safe for septic patients, provided it is administered correctly, then no patient should be denied such a therapy.

Conclusion

Co-administration of several of these treatments may be more effective than choosing only one of them. Research indicates that nutrients and herbs work together. For example, an RCT showed that the combined supplementation of omega-3 fatty acids + nano-curcumin reduces inflammatory processes (hsCRP and IL-6) more than monotherapy with either of them alone, suggesting a synergistic effect. [52] Another RCT showed that the combined administration of nigella sativa + vitamin D leads to faster recovery of a viral disease than monotherapy with either of them alone. [32]

Hashimoto-patients with Covid-19 who were treated with vitamin D, zinc and selenium had a 99% lower risk of hospitalization compared to those who did not receive treatment with these nutrients. [53] Also, in severely sick hospitalized patients suffering from a serious viral illness (Covid-19), co-administration of several vitamins, minerals, herbs, algae and probiotics in addition to standard care reduced the risk of death by almost 90% compared with standard therapy alone. A single compound would likely not have been so effective. It was the synergistic combination of several natural immunomodulatory substances that saved so many lives. Such a nutritional support system should also be prioritized to reduce mortality in hospitalized patients from sepsis or to prevent the incidence of sepsis. [54] The earlier the treatment starts during sepsis, the higher the chance of success.

Note: This article does not provide or replace medical advice, as it is for educational purposes only. Before taking any supplements or drugs or before making any lifestyle changes, consult a qualified (natural) therapist or orthomolecular practitioner who can provide personalized advice and details of risks and benefits based on your medical history and situation. Both (prescription-free) supplements and drugs can have side effects that are not listed in this article. Interactions between drugs and supplements can be possible in some cases. This article does not claim to list all potential benefits and risks (including side effects) of the described treatments. Also, some of the treatments described here should not be used before a surgery due to their strong anti-thrombotic efficacy. For example, it has been recommended not to administer curcumin pre-surgery for that reason.

(Max Langen has found that his own health problems were greatly alleviated by orthomolecular medicine. He is currently working on a book about it, and has plans to qualify as a therapist. Dr. Petra Wiechel is chief physician of the Swiss Mountain Clinic in Switzerland [ https://www.swissmountainclinic.com]. She is expert in biological and orthomolecular medicine, and treats her patients holistically.)

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Albert G. B. Amoa, MB.Ch.B, Ph.D. (Ghana)
Seth Ayettey, M.B., Ch.B., Ph.D. (Ghana)
Ilyès Baghli, M.D. (Algeria)
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