Chronic Fatigue & Low Energy: A Comprehensive Nutritional and Natural-Health Reference
1. Definition and Clinical Overview
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a serious, chronic, complex, and systemic disease associated with neurological, immunological, autonomic, and energy metabolism dysfunction (Institute of Medicine, 2015). Within the broader landscape of fatigue medicine, ME/CFS represents the most rigorously studied and severely disabling presentation of chronic low energy, but the term chronic fatigue also encompasses a continuum of persistent, unexplained exhaustion that may arise across many clinical and subclinical contexts.
ME/CFS is characterized by chronic, unexplained fatigue, a disabling payback following exertion ("post-exertional malaise"), and variably presenting multi-system symptoms, making it a complex disease that demands concerted biomedical investigation from disparate fields of expertise.
ME/CFS has been classified as a neurological disease by the World Health Organization (WHO) since 1969, initially under the name benign myalgic encephalomyelitis. Alternatively, on the basis of abnormalities in immune cells, ME/CFS is labelled a neuroimmune condition. The disease can further be regarded as a post-acute infection syndrome (PAIS) or an infection-associated chronic condition.
The condition can also be called systemic exertional intolerance disease (SEID). The prevalence of chronic fatigue syndrome has ranged from 0.2% to 0.7% in the general population. Anyone can get ME/CFS, but it is most common in people between 40 and 60 years old. Adult women are more likely to develop it than adult men.
2. Clinical Presentation and Symptoms
Individuals with ME/CFS experience a range of symptoms including significant impairment in function, post-exertional malaise, sleep impairment, cognitive issues, pain, orthostatic intolerance, flu-like symptoms, sensory intolerance, gastrointestinal and genitourinary issues.
The hallmark symptom is post-exertional malaise (PEM), a worsening of the illness that can start immediately or up to days after even minor physical or mental activity. This "crash" can last hours, days or several months. Further common symptoms include orthostatic intolerance — dizziness or faintness when upright — and pain.
One common symptom is severe fatigue. It does not get better with rest and is not directly caused by other medical problems. Other symptoms can include problems with thinking and concentrating, pain, and dizziness.
Fatigue, a commonly reported symptom, is defined as an overwhelming, debilitating, and sustained sense of exhaustion that decreases the ability to function and carry out daily activities. In the broader context of chronic low energy outside a formal ME/CFS diagnosis, this same definition applies — a persistent reduction in physical and mental capacity not accounted for by ordinary rest.
3. Body Systems Involved
Myalgic Encephalomyelitis is a serious, debilitating, chronic disease that affects multiple body systems, including the nervous system, the immune system, and the body's production of energy. Modern research has substantially expanded this picture:
3.1 Immunological System
Immune alterations include reduced natural killer cell cytotoxicity, T-cell exhaustion, abnormal B-cell subsets, and the presence of diverse autoantibodies, suggesting an autoimmune component. A systematic review showed that patients with CFS have abnormal peripheral blood mononuclear cell (PBMC) function, which typically manifests as decreased NK cell killing activity and imbalance of T cell subsets. In addition, the levels of inflammatory factors such as IL-4, IL-5, IL-7, IL-12p70, and TNF-α are elevated in patients with CFS, indicating a chronic low-grade inflammatory state.
3.2 Neurological and Autonomic Systems
Researchers with the NIH Intramural ME/CFS Study learned recently, in 2024, that infections may trigger immune system problems that lead to chemical changes in the brain, causing ME/CFS symptoms. Endothelial dysfunction driven by oxidative and nitrosative stress, along with autoantibody-mediated receptor interference, may explain orthostatic intolerance and impaired perfusion.
3.3 Energy Metabolism and Mitochondria
Metabolomic and mitochondrial studies identify impaired ATP generation, redox imbalance, and compensatory shifts toward alternative energy pathways underlying hallmark symptoms like post-exertional malaise. Low-grade inflammation induces a metabolic switch from energy-efficient oxidative phosphorylation to fast-acting, but less efficient, aerobic glycolytic energy production; increases reactive oxygen species; and reduces insulin sensitivity. These effects result in reduced glucose availability and, thereby, reduced cellular energy.
3.4 Neuroendocrine System
Neuroendocrine findings such as hypothalamic–pituitary–adrenal (HPA) axis hypofunction and altered thyroid hormone metabolism further compound metabolic and immune abnormalities. Cancer researchers have been at the forefront of investigating the possible biological mechanisms of fatigue, identifying inflammation, dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, and activation of the autonomic nervous system.
3.5 Gastrointestinal System
Gut dysbiosis and increased intestinal permeability may promote systemic inflammation and contribute to neurocognitive symptoms via the gut–brain axis. An NIH-funded study found that people with ME/CFS have different types of gut bacteria — microorganisms that live in the digestive tract and help the body digest food — that may help diagnose ME/CFS as well as increase understanding about how changes in the digestive system affect ME/CFS.
3.6 Metabolomic Landscape
Previous studies have identified irregularities in metabolites associated with energy metabolism, lipid metabolism, nucleotides, peptides, and cofactors and vitamins in ME/CFS patients. The evidence is mostly comprised of disturbances to immunological and inflammatory pathways, autonomic and neurological dysfunction, abnormalities in muscle and mitochondrial function, shifts in metabolism, and gut physiology or gut microbiota disturbances.
4. Contributing and Associated Factors
4.1 Infectious Triggers
Experts do not yet know the exact cause of ME, but many people start feeling the symptoms of ME after contracting a viral or other type of infection, or following surgery, physical trauma, or a change in hormonal status. A severe viral illness frequently predisposes the onset of CFS, while a number of pathogens have been linked to CFS. Although some patients develop CFS after an acute infection such as mononucleosis, some investigators believe it arises from the reactivation of a latent virus in the host, both resulting in a chronic low-level activation of the immune system.
4.2 Genetic Factors
Variants in multiple genes may affect the body's response to infection or chronic pain. Non-genetic physical, social, and environmental factors that people in the same household share can also affect who gets ME/CFS. Evidence is also beginning to emerge that chronic fatigue syndrome may be familial.
4.3 Immune Dysregulation
It is possible that the symptoms of ME result from an abnormal response by the immune system, most often to an infection. This can impact the brain and other systems of the body.
4.4 Metabolic and Mitochondrial Dysfunction
Based on omics and molecular biology, abnormal energy metabolism, oxidative stress, and mitochondrial dysfunction serve a central role in the pathogenesis of fatigue. The more CFS is investigated, the clearer it becomes that it is probably a metabolic dysfunction resulting in insufficient energy production.
4.5 Low-Grade Chronic Inflammation
A model of an imbalance in energy availability and energy expenditure as a consequence of low-grade inflammation has been proposed. Chronic low-grade inflammation can lead to reduced cellular-energy availability. There is also mounting evidence that behavioral-energy expenditure exceeds the reduced cellular-energy availability in patients with persistent fatigue, suggesting that an inability to adjust energy expenditure to available resources might be one mechanism underlying persistent fatigue.
4.6 HPA Axis and Circadian Disruption
Circadian-rhythm changes and sleep disturbances might mediate the effects of inflammation on cellular-energy availability and non-adaptive energy expenditure. Chronic illnesses are associated with underlying biological changes — inflammation, autonomic nervous system activation, and hypothalamic–pituitary–adrenal axis dysregulation — that appear to be associated with fatigue.
4.7 Heterogeneity of Precipitants
Proposed triggers include acute or chronic viral infections, reactivation of latent pathogens, significant physiological or psychological stressors, and genetic susceptibility. Collectively, ME/CFS appears to arise from a self-sustaining cycle of chronic inflammation, metabolic insufficiency, and neuroimmune imbalance.
5. Micronutrient Deficiencies Associated with Fatigue
Many nutrient deficiencies — including vitamin C, vitamin B complex, sodium, magnesium, zinc, folic acid, L-carnitine, L-tryptophan, essential fatty acids, and coenzyme Q10 — have been reported in patients with ME/CFS. The following reviews the principal micronutrients studied in relation to fatigue.
5.1 B-Vitamins
A key narrative review examined the scientific evidence supporting the role of vitamins and minerals in health outcomes related to fatigue, including nine vitamins (B1, B2, B3, B5, B6, B9, B8, B12, and C) and three minerals (iron, magnesium, and zinc) selected based on health claims authorised in Europe for these nutrients.
One of the most typical features of pyridoxine (vitamin B6) deficiency is microcytic anemia, due to defective hemoglobin biosynthesis and characterized by symptoms of weakness, tiredness, or fatigue. The importance of maintaining an adequate vitamin B6 status has been highlighted by the observation that iron supplementation could be ineffective in treating iron deficiency anemia in pregnant women who had vitamin B6 deficiency.
Deficiencies in folate (vitamin B9) can result in megaloblastic anemia, which produces symptoms of weakness and fatigue, headache, palpitations, and shortness of breath. Deficiencies in vitamin B12 are associated with mental and cognitive impairment, such as irritability, memory loss, depression, and cognitive disturbances up to dementia. In a hospital-based study, the most common clinical features of B12 deficiency were pallor (56.2%), fatigue (38.1%), anorexia (37.1%), and tingling sensations (32.1%).
5.2 Vitamin D
Recent evidence seems to link vitamin D deficiency to fatigue. The association between vitamin D status and fatigue has been assessed in cohorts of older subjects with and without fatigue. Subjects with fatigue showed lower levels of vitamin D as compared with those without fatigue.
A case report in PMC described a patient whose fatigue resolved following vitamin D supplementation. Possible mechanisms for clinical improvement include effects of vitamin D on components of inflammatory cascades, including tumor necrosis factor-alpha and prostaglandin D2, which result in a decrease in central nervous system homeostatic sleep pressure. More research is needed to determine if patients presenting with fatigue should be routinely screened for vitamin D deficiency, but clinicians should consider obtaining vitamin D levels in patients with unexplained fatigue, nonspecific musculoskeletal pain, and risk factors for vitamin D deficiency.
5.3 Iron
Iron is essential for hemoglobin synthesis and mitochondrial function. Iron deficiency anemia is among the most common reversible causes of fatigue worldwide. Iron is among the minerals whose health claims dealing with energy-related outcomes have been authorized in Europe. Evidence from the B6-iron interaction studies (see above) underscores how co-existing micronutrient deficiencies can render single-nutrient repletion incomplete.
6. Nutritional Supplements and Natural Ingredients
The following section separates traditional use from scientific evidence for each key substance. Evidence strength is characterized honestly according to what peer-reviewed sources show.
6.1 Coenzyme Q10 (CoQ10)
Traditional/Background Use: CoQ10 is not a classical herbal remedy but rather an endogenous lipid-soluble compound produced by the body. Its use as a nutritional supplement arose from biochemical research in the 1970s–1980s demonstrating its role in the mitochondrial electron transport chain. It is not associated with a specific ethnobotanical tradition.
Scientific Evidence: CoQ10 is a popular nutritional supplement, an antioxidant and an essential component of the mitochondrial electron transport chain. Several clinical studies have suggested that fatigue can be reduced by antioxidant supplementation. However, the data on this topic has been sparse to date.
A meta-analysis searched electronic databases for randomized controlled trials (RCTs) published from database inception to January 2022, implementing a random effects model among 13 RCTs with a total of 1,126 participants. CoQ10 was found to be effective in reducing fatigue. However, CoQ10 is effective in reducing fatigue in the CoQ10-only formulation, but not in the mixing compound, which might be associated with the lower dose of CoQ10 used in compound regimens.
A key RCT focused specifically on ME/CFS: A 12-week prospective, randomized, double-blind, placebo-controlled trial was conducted in 207 patients with ME/CFS, who were randomly allocated to one of two groups to receive either 200 mg of CoQ10 and 20 mg of NADH (n = 104) or matching placebo (n = 103) once daily. A significant reduction in cognitive fatigue perception and overall FIS-40 score and an improvement in health-related quality of life (HRQoL) from baseline were observed within the experimental group over time. Statistically significant differences were also shown for sleep duration at 4 weeks and habitual sleep efficiency at 8 weeks. Overall, these findings support the use of CoQ10 plus NADH supplementation as a potentially safe therapeutic option for reducing perceived cognitive fatigue and improving HRQoL in ME/CFS patients. Future interventions are needed to corroborate these clinical benefits.
The accumulating literature has identified a link between mitochondrial dysfunction and low-grade systemic inflammation in ME/CFS. Randomised controlled clinical trials have reported significant symptomatic benefits, particularly for fibromyalgia; further randomised controlled trials are required to confirm the efficacy of CoQ10 supplementation in patients with ME/CFS and long COVID.
Evidence Strength: Moderate for ME/CFS when combined with NADH; the evidence base for CoQ10 alone in ME/CFS is preliminary. Trials are small and methodological limitations persist.
6.2 NADH (Nicotinamide Adenine Dinucleotide, Reduced Form)
Traditional/Background Use: NADH is not an herbal remedy. Its study in fatigue arose from observations of impaired tryptophan/kynurenine metabolism and NAD+ biosynthesis in ME/CFS.
Scientific Evidence: Improvements in fatigue were observed for nicotinamide adenine dinucleotide hydride (NADH), probiotics, high cocoa polyphenol-rich chocolate, and a combination of NADH and coenzyme Q10 in a systematic review of nutritional interventions in ME/CFS. The kynurenine pathway plays a central role in cellular energy production through the production of nicotinamide adenine dinucleotide (NADH).
Some interventions — including L-carnitine and guanidinoacetic acid, oxaloacetate, CoQ10–selenium combination, NADH, and NADH-CoQ10 combination — showed significant reductions in fatigue in a 2025 PRISMA-compliant systematic review, though methodological limitations and inconsistent results hinder definitive conclusions.
Evidence Strength: Preliminary to moderate. Combination CoQ10 + NADH has the best current RCT support in ME/CFS, but sample sizes remain small.
6.3 L-Carnitine and Acetyl-L-Carnitine
Traditional/Background Use: L-carnitine is an endogenous amino-acid derivative found naturally in red meat. It has no deep classical ethnobotanical tradition, but has been used in sports nutrition since the 1980s based on its role in fatty-acid transport.
Scientific Evidence: The amino acid L-carnitine and its derivative acyl-L-carnitines are required for the transport of fatty acids into the mitochondria during the breakdown of lipids for the generation of metabolic energy in muscles and in the brain. One of the examined nutritional supplements for treatment in ME/CFS is acetyl-L-carnitine (ALC). It is a transporter of fatty acid and is involved in the energy production by catabolizing lipids in the brain and muscles.
Fourteen studies (N = 809) of heterogeneous designs were included in one systematic review; while some interventions including L-carnitine showed significant reductions in fatigue, methodological limitations, including small sample sizes and missing data, prevent firm conclusions.
Evidence Strength: Preliminary. Mechanistic rationale is clear, but large, well-controlled trials in ME/CFS are lacking.
6.4 Magnesium
Traditional/Background Use: Magnesium has been used since antiquity (e.g., Epsom salts) for muscular relaxation and general tonic effects, though its specific use for fatigue is more modern.
Scientific Evidence: A 2006 updated systematic review concluded that supplements of essential fatty acids and magnesium showed beneficial effects in only one or two trials, and that further rigorous trials of these interventions were required. A systematic review of RCTs has concluded that NADH and magnesium have proven beneficial effects in CFS. However, a 2011 review found insufficient evidence to recommend dietary supplements as a treatment for CFS/ME.
Evidence Strength: Weak to preliminary for fatigue specifically in ME/CFS. Evidence for benefit when correcting confirmed magnesium deficiency in broader fatigue contexts is mechanistically plausible but not well validated by large RCTs.
6.5 Rhodiola rosea
Traditional Use: Rhodiola rosea is grown at high altitudes and northern latitudes. Due to its purported adaptogenic properties, it has been studied for its performance-enhancing capabilities in healthy populations and its therapeutic properties in a number of clinical populations. It has a long history in traditional medicine in Russia and Scandinavia, where it was used to increase endurance, reduce fatigue, and improve resistance to physical and mental stress. The roots and rhizomes were traditionally prepared as decoctions and tinctures.
Scientific Evidence: Of 206 articles identified in a systematic search, 11 met inclusion criteria for review. Ten were described as RCTs and one as a CCT. Two of six trials examining physical fatigue in healthy populations reported Rhodiola rosea to be effective, as did three of five RCTs evaluating it for mental fatigue. However, all of the included studies exhibit either a high risk of bias or have reporting flaws that hinder assessment of their true validity. Research regarding Rhodiola rosea efficacy is contradictory.
An open-label clinical trial examined R. rosea specifically in subjects with prolonged or chronic fatigue symptoms. Rhodiola rosea roots and rhizomes are a herbal medicine for temporary relief of stress symptoms such as fatigue and sensed weakness, according to its herbal monograph context. None of the studies examining Rhodiola rosea for physical or mental fatigue measured outcomes consistently — no two studies reported the same outcomes — such that meta-analysis could not be performed.
Evidence Strength: Mixed/preliminary. Some positive signals in human trials for mental fatigue and stress-related exhaustion, but all reviewed RCTs have high or unclear risk of bias, preventing firm conclusions.
6.6 Ashwagandha (Withania somnifera)
Traditional Use: Ashwagandha (Withania somnifera) is a herb commonly used in Ayurvedic medicine to promote youthful vigor, enhance muscle strength and endurance, and improve overall health. Ashwagandha holds a significant place in Ayurvedic medicine, recognized as both a "rasayana" — a rejuvenating tonic — and an "adaptogen." In classical Ayurveda, the dried root was powdered and taken with warm milk or ghee, particularly to restore vitality in debilitated individuals.
Scientific Evidence: Multiple RCTs have been conducted. Based on the Chalder Fatigue Scale, there was a statistically significant reduction in fatigue symptoms in the ashwagandha group compared to the placebo group (p = 0.016) in a randomized double-blind placebo-controlled trial in adults with high stress and fatigue. However, in overweight middle-to-older age adults experiencing high stress and fatigue, compared to placebo, ashwagandha did not have a significantly greater impact on perceived stress levels. However, based on secondary outcome measures, it may have anti-fatigue effects, possibly via its impact on the autonomic nervous system. Further research is required to expand on these current findings.
In healthy athletic adults, RESTQ assessment yielded better outcomes for fatigue recovery, lack of energy, and fitness analysis (p < 0.0001). The enhanced antioxidant level was significant (p < 0.0001) in the ashwagandha group. The findings suggest that ashwagandha root extract can successfully enhance cardiorespiratory endurance and improve quality of life in healthy athletic adults. That particular RCT enrolled 50 participants and used 300 mg twice daily for 8 weeks.
Analyzed trials involved 10–590 participants, aged 18–75 years, both healthy individuals and patients with stress-related or functional disorders. Interventions included standardized extracts at daily doses of 120–1,000 mg for W. somnifera and 290–1,500 mg for R. rosea, with supplementation lasting 3–16 weeks.
Evidence Strength: Moderate for stress-related fatigue and physical endurance in healthy or mildly stressed populations. Evidence in clinical ME/CFS is limited. Between-study variability in extract standardization limits generalizability.
6.7 Panax Ginseng
Traditional Use: Panax ginseng (Asian or Korean ginseng) has been used for over 2,000 years in traditional Chinese and Korean medicine as a restorative tonic — classified as a "qi-tonifying" herb — intended to replenish vital energy (qi), improve mental clarity, and combat fatigue. Preparations traditionally involved slow decoctions of the dried root, often combined with other tonic herbs.
Scientific Evidence: Numerous active compounds have been identified in Panax ginseng, including ginsenosides, ginseng polysaccharides, and ginseng protein. Ginsenosides, the most important ingredients of ginseng, have been proven to have various pharmacological activities including anti-fatigue, anti-oxidation, neuroprotection, anti-inflammation, and anti-diabetes effects.
A systematic review of 102 studies reveals that ginsenosides undergo biotransformation mediated by the gut microbiota into bioactive metabolites, enhancing their bioavailability by 3- to 5-fold. Three core mechanisms were identified: inhibition of the TLR4/NF-ÎşB pathway, upregulation of tight junction proteins strengthening intestinal barrier function, and selective gut microbiota modulation increasing short-chain fatty acid production and activating AMPK/SIRT1 signaling.
Evidence for ginseng specifically in ME/CFS fatigue remains limited. A systematic review noted ginseng has been studied for fatigue reduction in ME/CFS and other conditions, with potential gut microbiome-mediated pharmacokinetics noted as a mechanism, but high-quality RCT evidence specifically in ME/CFS populations is sparse. Most human trials showing fatigue-related benefit have been conducted in cancer-related fatigue, general stress, or healthy volunteers.
Evidence Strength: Mechanistically plausible; some clinical evidence for fatigue in cancer patients and general stress-related exhaustion. Evidence specific to ME/CFS is preliminary and insufficient for firm conclusions.
6.8 Probiotics
Traditional Use: Fermented foods containing live cultures (yogurt, kefir, fermented vegetables) have been consumed across many traditional food cultures for millennia, prized for digestive and general health benefits, though their explicit use for fatigue is modern.
Scientific Evidence: Improvements in fatigue were observed for probiotics among the nutritional interventions reviewed in the Campagnolo et al. systematic review of ME/CFS. Gut dysbiosis and increased intestinal permeability may promote systemic inflammation and contribute to neurocognitive symptoms via the gut–brain axis in ME/CFS, providing biological rationale for probiotic intervention. However, this review identified insufficient evidence for the use of nutritional supplements and elimination or modified diets to relieve CFS/ME symptoms as a whole, and probiotics were evaluated in very few trials.
Evidence Strength: Preliminary. Mechanistic basis is strong (gut-brain axis), but clinical trial data in ME/CFS specifically are scarce and limited by small sample sizes.
7. Dietary Factors
CFS/ME is characterised by unexplained fatigue for at least 6 months accompanied by a diverse but consistent set of symptoms. Diet modification and nutritional supplements could be used to improve patient outcomes, such as fatigue and quality of life.
Seventeen studies met the inclusion criteria in a systematic review of dietary and nutritional interventions in ME/CFS. Of these, 14 different interventions were investigated. Many studies did not show therapeutic benefit on CFS/ME.
One RCT compared a polynutrient supplement containing several vitamins, minerals, and coenzymes, taken twice daily, with a placebo for 10 weeks, but found no difference in fatigue scores. Supplements may benefit CFS/ME patients with specific nutritional deficiencies. A biochemical test for deficiencies should be performed before treatment in order to guide treatment choices.
The role of elimination diets (e.g., gluten-free, low-FODMAP) has been investigated in ME/CFS given the high prevalence of gastrointestinal symptoms, but the systematic review literature has not established a therapeutic benefit from elimination diets in the absence of a confirmed co-existing condition such as non-celiac gluten sensitivity or irritable bowel syndrome. Overall, the dietary intervention literature in ME/CFS is characterized by small samples, heterogeneous designs, and predominantly negative or inconclusive outcomes.
8. Lifestyle Factors
8.1 Physical Activity and Exercise
A systematic review and meta-analysis targeting structured therapeutic exercise interventions, including aerobic training, resistance exercises, and mind-body therapies, included 11 studies (7 RCTs, n = 2,276 participants), and showed significantly significant reductions in fatigue in both the short term and medium term. However, it is important to note the contested status of graded exercise therapy (GET) for ME/CFS specifically. In populations with confirmed post-exertional malaise, GET has been removed from UK NICE guidelines following evidence that it may worsen symptoms in some patients with ME/CFS. The exercise data apply more broadly to fatigue syndromes without confirmed PEM.
8.2 Sleep
Circadian-rhythm changes and sleep disturbances might mediate the effects of inflammation on cellular-energy availability and non-adaptive energy expenditure. Unrefreshing sleep is among the core diagnostic criteria for ME/CFS. Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) are recommended evidence-based treatments for CFS, with research supporting their effectiveness in reducing fatigue and functional impairment. However, little research has focused on the effect of these treatments on sleep, despite high reported sleep disturbance in CFS.
8.3 Stress and Psychological Factors
Findings to date suggest that physiological and psychological factors work together to predispose an individual to the illness and to precipitate and perpetuate the illness. Disorders in the neuro-endocrine-immune network and dysfunction of the microbiome-gut-brain axis constitute key systemic integration mechanisms through which psychological stress may translate into physical fatigue.
8.4 Limitations of the Evidence Base
Despite the widespread use of dietary supplements among ME/CFS patients to alleviate fatigue and associated symptoms, evidence remains inconclusive. While CoQ10 combined with NADH or selenium, NADH, L-carnitine, GAA, and oxaloacetate showed significant reductions in fatigue, inconsistencies in participant data and methodological limitations were evident in most studies. No firm conclusions can be drawn from the studies' results due to small sample sizes and missing data.
ME/CFS research and patient treatment have been challenged by the lack of diagnostic biomarkers, and finding these is a prominent direction of current work. Due to the variability of non-overlapping symptom presentation or precipitating events, the initiation of body-wide pathological cascades with similar outcomes stemming from different causes may be implicated in the condition. This heterogeneity substantially complicates the interpretation of nutritional and lifestyle intervention trials.
References
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