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Evidence-based medicine

What we know, what remains uncertain, and what has not been proven.

A critical review in U.S. English, with transparent evidence ratings, practical limits, and links to sources readers can verify.

Browse by subject

From the article to its evidence.

All 15 articles in the Knowledge Library are represented here, alongside complementary reviews: 19 topics in 6 areas. Each topic brings together sources, limitations and related MERHI ONE reading.

How we rate evidence

Four levels for communicating science honestly.

This is an educational editorial synthesis—not a formal GRADE assessment of one narrowly framed clinical question. Ratings consider study quality, consistency, applicability, and agreement with recognized guidelines.

Ratings apply to specific claims. Summaries of concepts and methods identify the source type and its limitations, without assigning a single rating to an entire topic.

Strong Convergent guidelines and robust studies.Moderate A probable benefit or association, with relevant limitations.Weak Small, indirect, observational, or inconsistent studies.Insufficient No reliable clinical support for routine use or the promoted claim.

Tests and clinical assessment

Back to topics ↑

Clinical reasoning and test interpretation

Normal results with persistent symptoms

Reference intervals

A range for comparison does not establish a diagnosis. The 95% model is a statistical convention for many quantitative tests, not a person's probability of being healthy.

Timbrell, 2024 — narrative review

The clinical question

A result changes the probability of a hypothesis. Its meaning depends on the question, the test, and the clinical context.

Grimes & Schulz, 2005 — methodological article

Persistent symptoms

A position paper calls for contextual care and reduced stigma. It does not establish the cause of an individual's symptoms or prove that all symptoms have the same explanation.

Toussaint et al., 2025 — position paper, online in 2024

Read the illustrated article and full references →

Guideline and clinical reasoning

Multiple symptoms together

Start with the history, not a test panel

Fatigue, mood changes, hair loss and low sexual desire may have different or coexisting causes. Assessment considers timing, medicines, sleep, diet, examination and clinical hypotheses; further tests depend on the findings. [1]

A vignette teaches; it does not establish efficacy

The article uses a composite vignette to explain how care is organized. Improvement described in a scenario, even one resembling a real case, does not establish which intervention worked or confirm a hormonal or nutritional cause. [2]

Sources supporting this summary

Kornder N et al. Tiredness/Fatigue—S3 guideline update. 2023.Guideline update
Gagnier JJ et al. The CARE guidelines: consensus-based clinical case reporting guideline development. Deutsches Ärzteblatt International. 2013.Reporting guideline; not evidence of treatment effect

KDIGO guideline

Kidney health

Filtration and albuminuria complement each other

Kidney assessment combines clinical context, estimated glomerular filtration rate and urine albumin when indicated. A creatinine value within the laboratory range does not summarize overall kidney health. [1]

Persistence and limitations affect interpretation

Chronic kidney disease requires evidence of abnormalities persisting for at least three months. Muscle mass and other factors affect creatinine; in selected situations, combining it with cystatin C improves filtration estimates. [1][2]

Sources supporting this summary

KDIGO. 2024 CKD Guideline — Top 10 Takeaways for Primary Care Physicians: Evaluation.Official guideline summary
KDIGO. CKD Evaluation and Management.Guideline and update status

WHO and biomarker validation

Beyond your biological age score — clinical assessment

Ability and context

Healthy aging, as framed by the World Health Organization, focuses on the abilities that support well-being and on the environment in which a person lives. That perspective is broader than a laboratory score and allows personal priorities to remain part of the assessment. [1]

Validation and clinical utility

A published association is not enough to answer all of those questions. Biomarker validation is specific to the measure and its intended use; clinical utility requires evidence relevant to the decision being made. [2]

Sources for the article and this summary

Explore each source and its citation in the article. Institutional guidance, scientific reviews and individual studies serve different purposes.

World Health Organization. Ageing. Official topic page.WHO · institutional overview of ageingFind this reference in the article →
Moqri M, et al. Validation of biomarkers of aging. Nature Medicine. 2024;30:360–372. DOI: 10.1038/s41591-023-02784-9.Scientific review · validation of aging biomarkersFind this reference in the article →
World Health Organization. Integrated care for older people (ICOPE): guidance for person-centred assessment and pathways in primary care. 2nd ed. 2025. ISBN 9789240103726.WHO · ICOPE guidance for person-centred assessment, 2nd edition (2025)Find this reference in the article →
Waziry R, et al. Effect of long-term caloric restriction on DNA methylation measures of biological aging in healthy adults from the CALERIE trial. Nature Aging. 2023;3:248–257. DOI: 10.1038/s43587-022-00357-y.CALERIE study · analysis of DNA methylation measures in a randomized trialFind this reference in the article →
U.S. Food and Drug Administration. FDA Facts: Biomarkers and Surrogate Endpoints. Official institutional webpage.FDA · institutional explanation of biomarkers and surrogate endpointsFind this reference in the article →

Muscle strength · Claim-specific assessment

Losing Strength? When to Seek a Medical Evaluation

Strong · Clinical distinction

Fatigue and weakness are not equivalent

Fatigue describes lack of energy; weakness describes reduced muscle strength. They may coexist and need characterization. This is established clinical guidance, not a treatment-effect estimate. [1][2]

Strong · Clinical guidance

Persistent or worsening weakness deserves assessment

History, the pattern of weakness, medicines, and examination guide assessment. This applies to symptomatic adults; it does not diagnose sarcopenia or justify universal test panels. [2]

Diagnostic consensus · Not an efficacy rating

EWGSOP2 assigns different roles to strength, quantity, and performance

Low strength indicates probable sarcopenia; low muscle quantity or quality adds confirmation, and performance helps assess severity. This consensus mainly concerns older and at-risk people, not a universal operational definition. GLIS 2024 is conceptual. [3][9]

Moderate · Benefit with limitations

Resistance training may improve strength and some functional tests

A review of 24 trials in 951 adults aged 60 or older with sarcopenia found average gains in some, but not all, tests. Pooled gains did not exceed the authors’ thresholds for clinically important differences. This does not guarantee regained independence or establish a universal training load. [4]

Insufficient · Universal supplementation

Whey is not a proven solution for every case of weakness

A meta-analysis in older adults found variable results: no consistent improvement in grip strength or physical performance, although some analyses with training favored lower-limb strength. It does not support whey for everyone. ESPEN recommends individualized nutrition; addressing inadequate intake or malnutrition is a different question. [5][6]

Insufficient · Self-diagnosis from a single measurement

A scale alone does not explain loss of strength

Validated bioelectrical impedance can contribute to assessment but depends on the device, equation, population, and hydration. This rating concerns inadequate support for self-diagnosis or determining the cause from one reading—not a claim that the clinical tool is useless. [3]

Strong · Official emergency guidance

Sudden one-sided weakness requires immediate action

This may indicate stroke, whether or not it occurs with changes in speech, face, vision, or balance. Call 911 in the U.S. or SAMU 192 in Brazil. This official guidance applies at any age, not only to people with sarcopenia. Do not wait for a routine appointment. [7][8]

Sources supporting this summary

MedlinePlus. Fatigue. Revisão / review: 2025.Clinical information for patients
MedlinePlus. Weakness. Revisão / review: 2024.Clinical guidance; not a treatment trial
Cruz-Jentoft AJ et al. Sarcopenia: revised European consensus on definition and diagnosis (EWGSOP2). Age and Ageing. 2019;48:16–31. doi:10.1093/ageing/afy169.European diagnostic consensus
Yan R et al. Optimal resistance training prescriptions to improve muscle strength, physical function, and muscle mass in older adults diagnosed with sarcopenia: a systematic review and meta-analysis. Aging Clinical and Experimental Research. 2025;37:320. doi:10.1007/s40520-025-03235-w.Systematic review of 24 trials; bibliographic record and abstract checked
Al-Rawhani AH et al. Effectiveness of whey protein supplementation on muscle strength and physical performance of older adults: A systematic review and meta-analysis of randomized clinical trials. Clinical Nutrition. 2024;43(10):2412–2426. doi:10.1016/j.clnu.2024.08.033.Systematic review and meta-analysis; bibliographic record and abstract checked
Volkert D et al. ESPEN practical guideline: Clinical nutrition and hydration in geriatrics. Clinical Nutrition. 2022;41:958–989. doi:10.1016/j.clnu.2022.01.024.Geriatric nutrition guideline
Ministério da Saúde. Acidente Vascular Cerebral (AVC).Official emergency guidance — Brazil
National Institute of Neurological Disorders and Stroke (NINDS). Stroke: Signs and Symptoms.Official emergency guidance — United States
Kirk B et al. The Conceptual Definition of Sarcopenia: Delphi Consensus from the Global Leadership Initiative in Sarcopenia (GLIS). Age and Ageing. 2024;53:afae052.Conceptual consensus; not a universal diagnostic cutoff
Freedman M. Weakness. Merck Manual Consumer Version. 2025.Clinical reference — warning signs

Heart and circulation

Back to topics ↑

Blood pressure

My blood pressure was high. What now?

Guideline recommendation

One reading usually does not confirm hypertension

Correct technique, repeated readings, and out-of-office confirmation help distinguish sustained hypertension from white-coat or masked patterns. Concerning acute symptoms require immediate assessment.

Read the practical guide and references

Key references

Consensus and guideline

LDL-C, non-HDL-C and ApoB

Carried cholesterol and particle number

LDL-C and non-HDL-C measure carried cholesterol; ApoB reflects the concentration of atherogenic particles. Results can be discordant, particularly in metabolic conditions, and add different information to assessment. [1]

Targets depend on risk

Decisions combine medical history, associated conditions, cardiovascular risk and response to care. A laboratory reference range is not automatically a treatment target, and a marker does not replace clinical assessment. [1][2]

Sources supporting this summary

Soffer DE et al. Role of apolipoprotein B in the clinical management of cardiovascular risk in adults. National Lipid Association. 2024.Expert clinical consensus
Rached FH et al. Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose. 2025.Brazilian clinical guideline

Inherited cardiovascular risk

Lipoprotein(a): risk, testing, and treatment uncertainty

Evidence about a risk factor is not the same as evidence that a medication improves health. This update separates what the test tells us, what guidelines recommend, and what the 2026 result showed about one specific intervention.

Strong evidence

What the test tells us

Elevated Lp(a) is a causal, mostly inherited risk factor for atherosclerotic cardiovascular disease and calcific aortic valve stenosis. Risk is continuous: one result does not predict that an event is inevitable or determine treatment by itself.

Strong evidence

What guidelines recommend

The 2026 ACC/AHA guideline and 2024 NLA update recommend at least one adult measurement; the 2025 ESC/EAS update says it should be considered, and Brazil's 2025 guideline recommends it when available. Molar thresholds differ by region and are not a conversion formula.

Topline result; full analysis pending

What has been shown about the intervention

On September 4, 2026, the sponsor reported that Lp(a)HORIZON did not meet its primary cardiovascular endpoint in the overall population despite lowering Lp(a) with pelacarsen. This is a phase 3 headline result; event rates, effect estimates, subgroup findings, and the complete analysis have not yet been presented publicly.

Read the full Lp(a) article

Key references

Guideline and observational study

Coronary calcium and overall risk

CAC answers a specific question

Coronary calcium scoring detects calcified coronary plaque. It can refine prevention decisions in selected people without symptoms when meaningful uncertainty remains after risk assessment. [1]

Different tests, complementary information

LDL-C/ApoB, Lp(a) and CAC describe different aspects of risk. Cohort studies show associations between Lp(a), CAC and cardiovascular events; they do not prove that scanning everyone improves outcomes. [1][2]

Sources supporting this summary

Rached FH et al. Diretriz Brasileira de Dislipidemias e Prevenção da Aterosclerose. 2025.Brazilian guideline; selective CAC use
Mehta A et al. Independent Association of Lipoprotein(a) and Coronary Artery Calcification With Atherosclerotic Cardiovascular Risk. JACC. 2022.Observational analysis of MESA and DHS cohorts

Neurologic emergency

Stroke and transient ischemic attack (TIA) warning signs

Stroke can cause sudden trouble with balance, vision, facial droop, arm or leg weakness, speech, or understanding. Time-sensitive treatment can reduce disability.

Strong evidence

Sudden neurologic symptoms require emergency care

Use BE FAST: Balance, Eyes, Face, Arm, Speech, Time. Note the last time the person was known to be well and call emergency services immediately.

Moderate evidence

BE FAST is a screening aid, not a rule-out test

Some strokes cause severe dizziness, poor coordination, double vision, confusion, or other sudden deficits. Missing one classic sign does not exclude stroke.

Weak evidence

Vague symptoms days earlier reliably predict a future stroke

Isolated fatigue, headache, or tingling has many causes. A TIA is different: a sudden focal neurologic deficit that improves still requires emergency evaluation.

Insufficient clinical evidence

Waiting, puncturing fingertips, or giving medicine at home

These actions do not treat stroke and may delay time-sensitive care. Symptoms that resolve still require urgent evaluation.

Key references

Metabolism and diabetes

Back to topics ↑

Integrated assessment and clinical trial

Metabolic health

Metabolic health is more than glucose

Blood pressure, waist size, glucose, lipids, habits and history help describe the overall picture. Metabolic syndrome describes a cluster of risk factors; no single test captures overall metabolic health. [1]

Prevention has evidence within the studied context

In the Diabetes Prevention Program, a structured lifestyle intervention reduced new diabetes cases in adults at high risk. The result supports supervised prevention without promising the same individual benefit for everyone. [2]

Sources supporting this summary

NHLBI/NIH. Metabolic Syndrome.Official clinical information
Knowler WC et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. NEJM. 2002.Randomized clinical trial

Diagnostic criteria and test limitations

Glucose, A1C and insulin

Glucose and A1C answer different questions

Glucose describes the time of sampling; A1C estimates glucose exposure over months. Anemia, changes in red blood cells and some hemoglobin variants can complicate A1C interpretation. [1]

Insulin alone does not diagnose diabetes

Diagnostic criteria use plasma glucose and/or A1C under defined conditions. Assessing insulin resistance has limitations; fasting insulin and HOMA-IR do not replace diabetes criteria or individual assessment. [2][3]

Sources supporting this summary

NIDDK/NIH. The A1C Test & Diabetes.Official information on the test and interference
NIDDK/NIH. Diabetes Tests & Diagnosis.Diagnostic criteria and confirmation
NIDDK/NIH. Insulin Resistance & Prediabetes.Official clinical information

Nutrition and glucose

Diabetes and breakfast

There is no universal diabetes breakfast. The effect of a meal depends on carbohydrate amount and quality, fiber, protein, fat, medications, activity, and individual glucose response.

Strong evidence

The overall eating pattern matters more than one food

Guidelines support individualized plans emphasizing vegetables, legumes, whole fruit, whole grains, and appropriate protein sources while limiting sugar-sweetened beverages and highly refined foods.

Moderate evidence

Protein and fiber may reduce the meal’s glucose rise

Small trials suggest that replacing a refined-carbohydrate breakfast with a meal containing more protein and/or fiber can reduce the post-meal glucose rise in some settings. The effect varies.

Weak evidence

One required meal time or composition for everyone

Meal timing may influence glucose, but studies are heterogeneous. Routine, hunger, medications, hypoglycemia risk, culture, and preferences matter.

Insufficient clinical evidence

A single food causes, cures, or reverses type 2 diabetes

No isolated food does so. One continuous glucose monitor reading also cannot diagnose diabetes or prove that a food must be banned for everyone.

Key references

Read the full breakfast article

Metabolism and weight

Tirzepatide: benefits, risks, and limits

In the United States, Mounjaro and Zepbound contain the same active ingredient but have different FDA-approved indications. Tirzepatide is prescription medication and requires individual screening and follow-up.

Strong evidence

Lower A1C and body weight in the populations studied

Randomized trials show clinically meaningful reductions in A1C and body weight in selected adults with type 2 diabetes and/or obesity. Gastrointestinal adverse effects are common, especially during dose escalation.

Moderate evidence

Benefits beyond the scale depend on the population

Trials support benefits in selected obesity-related conditions, including obstructive sleep apnea. Results from one population should not be assumed for every person seeking weight loss.

Weak evidence

Short-term cosmetic use outside trial populations

Major trials do not establish safety or benefit for normal-weight adults, improvised dosing, a few weeks of use, or unstudied drug combinations.

Insufficient clinical evidence

Guaranteed weight loss or risk-free self-medication

No response is guaranteed. Unapproved, counterfeit, or improperly compounded products may have incorrect ingredients, concentration, sterility, storage, or labeling.

Key references

Read the full tirzepatide article

Nutrition and supplements

Back to topics ↑

Food choices

Bread, “high-protein” products, fiber, and carbohydrates

“Flourless,” “keto,” and “high protein” are product descriptions—not automatic seals of health. Compare the serving size, total carbohydrate, fiber, protein, sodium, saturated fat, ingredients, and the whole meal.

Strong evidence

Fiber-rich foods and whole grains support metabolic health

Eating patterns rich in fiber, especially from minimally processed foods, are associated with better metabolic outcomes. Replacing some refined grains with whole grains and legumes is consistent with major guidelines.

Moderate evidence

Pairing carbohydrate with protein and fiber may blunt a glucose spike

A mixed meal may slow absorption and improve satiety, but the effect depends on the recipe and portion. A “high-protein” item can still be high in calories, sodium, or saturated fat.

Weak evidence

Glycemic index alone determines whether bread is healthy

Glycemic index can be informative, but preparation, processing, other foods, and the person all modify the response. Glycemic load and nutrient density matter too.

Insufficient clinical evidence

Flourless bread causes weight loss or controls diabetes by itself

Removing flour does not guarantee fewer carbohydrates, fewer calories, or a better glucose response. No bread substitutes for an overall treatment and nutrition plan.

Key references

Deficiency, safety and differential diagnosis

Zinc and taste changes

Altered taste does not confirm zinc deficiency

Deficiency can affect taste, but taste changes also have other causes. History, medicines, oral health and risk factors guide assessment. Serum zinc has limitations and needs context. [1][2]

More zinc does not mean more benefit

Excessive exposure can cause digestive symptoms and, over time, copper deficiency and neurological problems. Assessment must consider the sum of supplements and products, not just one label. [1]

Sources supporting this summary

NIH Office of Dietary Supplements. Zinc — Fact Sheet for Health Professionals.Official technical synthesis with references
NIDCD/NIH. Taste Disorders.Official clinical information

Hormones and thyroid

Back to topics ↑

Women’s health

Hormone testing after age 35

There is no single hormone panel every woman needs at 35. Symptoms, menstrual pattern, age, medications, reproductive goals, and personal history guide evaluation.

Strong evidence

Typical menopause is usually a clinical diagnosis

For otherwise healthy people with compatible symptoms and menstrual changes, routine hormone testing is generally not needed to confirm typical menopause. Menopausal hormone therapy can be effective for appropriate symptoms after individualized risk assessment.

Moderate evidence

Testing is useful in selected situations

FSH and other tests may help with suspected primary ovarian insufficiency, unexplained amenorrhea, atypical timing, or genuine diagnostic uncertainty.

Weak evidence

Broad repeated panels in people without symptoms

Testing many hormones without a clinical question increases incidental findings and may lead to unnecessary labels or treatment. Salivary hormone testing is not validated for routine dose adjustment.

Insufficient clinical evidence

Universal anti-aging replacement or “safer” compounded hormones

Hormone therapy should not be sold as a universal strategy for rejuvenation, weight loss, or prevention of dementia or heart disease. Compounded products are not proven safer or more effective than FDA-approved therapies.

Key references

Thyroid health

Hypothyroidism: diagnosis and treatment

Fatigue, weight change, constipation, dry skin, and mood symptoms are nonspecific. Diagnosis requires symptoms, history, examination, and appropriate testing—not an online symptom list.

Strong evidence

TSH and free T4 are the foundation of primary hypothyroidism evaluation

TSH is commonly the initial test, and free T4 helps classify the abnormality. Levothyroxine is the standard treatment for overt primary hypothyroidism, with individualized dosing and monitoring.

Moderate evidence

Subclinical hypothyroidism requires context

When TSH is elevated and free T4 is normal, the TSH value and persistence, age, symptoms, antibodies, pregnancy status, and cardiovascular risk affect decisions.

Weak evidence

T4/T3 combination or desiccated thyroid for every persistent symptom

Studies have not shown consistent superiority over levothyroxine. Selected cases require careful evaluation and review of other causes; switching is not automatic.

Insufficient clinical evidence

Routine reverse T3, thyroid detoxes, or iodine without deficiency

Reverse T3 is not recommended for routine thyroid assessment. Supplements and excess iodine may cause or worsen thyroid dysfunction.

Key references

Memory and cognition

Back to topics ↑

Cognition

Memory concerns and possible early signs of Alzheimer’s disease

Occasional lapses are common. Progressive change is more concerning—especially when it affects independence, finances, navigation, work, communication, or safety.

Strong evidence

Persistent or progressive symptoms deserve a structured evaluation

Evaluation combines the history, input from a trusted person when appropriate, medication review, sleep and mood assessment, a neurologic examination, cognitive testing, and selected laboratory or imaging studies. No single test establishes the diagnosis.

Moderate evidence

Clinicians should look for contributing and potentially treatable factors

Depression, sleep apnea, sedating or anticholinergic drugs, thyroid disease, vitamin B12 deficiency, hearing loss, alcohol use, and vascular disease can contribute. Treating a contributor is appropriate but may not reverse a coexisting neurodegenerative disorder.

Weak evidence

Omega-3 or vitamins as general memory enhancers

Trials do not show consistent cognitive benefit from routine supplementation in adults without a documented deficiency. Vitamin B12 is appropriate when a deficiency or another clinical indication is present.

Insufficient clinical evidence

Online protocols or methylene blue as a routine diagnosis or treatment

No reliable clinical evidence or guideline supports these approaches for routine treatment of memory loss or Alzheimer’s disease. Online quizzes are not diagnostic tests.

Key references

Read the full memory article

Professional responsibility

Health education without remote diagnosis, prescribing, or promises.

This material is general education. Dr. Elias is registered in Brazil, not the United States; this website does not provide U.S. medical services. Professional communication follows Brazilian CFM Resolution No. 2,336/2023.

View the Brazilian CFM rule

Organization, addition of the seven missing topics and source checks for those summaries completed September 20, 2026. BIOAGE: topic labels, sources and related links updated September 27, 2026. Earlier reviews and each article’s scientific review date are preserved. Medical evidence changes; pages are reviewed after major guidelines, safety alerts, or new evidence that may change a conclusion.

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Related reading from MERHI ONE Global, an independent health education project, to explore concepts, evidence and limitations.

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