Vitamins

Administrative Information and Communication

• Preferred Communication Channel: Students must use the Canvas Inbox for all course-related "email" communication to Dr. Gerber. Standard MWU email should be avoided.

• Subject Line Protocol: Messages should include succinct subject lines (e.g., "Questions about group project") to facilitate efficient and quick responses.

• Response Timeframe: Every effort is made to respond to Canvas Inbox messages within 48 hours.

• Office Hours: Conducted via Microsoft Teams on Wednesdays from 12:00 PM to 12:30 PM. This is a recurring meeting, and the access link is provided in the Canvas Announcements.

Fundamental Definitions and Nutrient Intake Standards

• Dietary Reference Intakes (DRIs): Developed by the Food and Nutrition Board (FNB) at the Institute of Medicine (IOM) of The National Academies (formerly the National Academy of Sciences). DRIs are a set of reference values used to plan and assess nutrient intakes for healthy people. These values vary specifically by age and gender.

• Recommended Dietary Allowance (RDA): The average daily level of intake sufficient to meet the nutrient requirements of nearly all ($97\%-98\%$) healthy individuals.

• Adequate Intake (AI): This value is established when evidence is insufficient to develop an RDA. It is set at a level assumed to ensure nutritional adequacy.

• Tolerable Upper Intake Level (UL): The maximum daily intake that is unlikely to cause adverse health effects across the general population.

Trends in Dietary Supplement Use (1999–2012)

According to data published in JAMA (2016; 316:1464), overall dietary supplement use among U.S. adults remained stable between 1999 and 2012. However, only $23\%$ of all supplement products were used based on the recommendation of a healthcare provider.

• Decreased Usage:

  • Multivitamins: Decreased from $37\%$ to $31\%$.

  • Vitamin C: Decreased from $42\%$ to $36\%$.

  • Vitamin E: Decreased from $41\%$ to $34\%$.

  • Ginseng: Decreased from $6\%$ to $2\%$.

• Increased Usage:

  • Fish oil: Increased from $1\%$ to $12\%$.

  • Vitamin D: Increased from $5\%$ to $19\%$.

• No Change in Usage:

  • Glucosamine: Remained at approximately $3\%$.

  • Chondroitin: Remained at approximately $2\%$.

Nutritional Supplements for Age-Related Eye Disease (AMD)

Age-Related Eye Disease Study (AREDS - 2001)

• Participants: $4,000$ patients with Age-Related Macular Degeneration (AMD).

• Median Age: $69$ years.

• Follow-up Duration: Average of $6.3$ years.

• Experimental Intervention:

  • Vitamin C: $500\,mg$

  • Vitamin E: $400\,\text{units}$

  • Beta-carotene: $15\,mg$

  • Zinc: $80\,mg$

  • Copper: $2\,mg$

• Efficacy Summary: To prevent one patient from progressing to severe macular degeneration, clinicians must treat $10$-$22$ high-risk patients for $5$ years.

• Outcomes by AMD Stage:

  • Early AMD: No benefit observed.

  • Intermediate AMD (Dry): Benefit demonstrated; reduction in the development of advanced AMD.

  • Advanced AMD (Dry or Wet): Benefit demonstrated; reduced risk for vision loss.

Age-Related Eye Disease Study 2 (AREDS2 - 2013)

• Participants: $4,203$ participants with AMD.

• Intervention Groups:

  1. Lutein ($10\,mg$) + Zeaxanthin ($2\,mg$) added to the original AREDS formulation.

  2. DHA ($350\,mg$) + EPA ($650\,mg$) added to the original AREDS formulation.

  3. Combination of Lutein + Zeaxanthin AND DHA + EPA added to AREDS.

  4. Placebo added to AREDS.

• Conclusion: In primary analyses, the addition of lutein, zeaxanthin, DHA, or EPA to the original AREDS formulation did not further reduce the risk of progression to advanced AMD.

Labeling and Public Perception Issues

• Misleading Labels: many best-selling products do not follow the proven AREDS formula despite marketing claims.

• FDA Status: Because these products are not considered drugs, the FDA does not test or approve them for efficacy before they reach the market.

• Clinical Limitations: AREDS results do not apply to all populations; patients should proceed with caution.

Vitamin D: Guidelines and Clinical Indications

Major Reference Organizations

• Endocrine Society Clinical Practice Guideline (2011)

• World Health Organization (WHO)

• Institute of Medicine (IOM) Systematic Review

• Vitamin D Council

START Criteria (Screening Tool to Alert to Right Treatment, Version 2)

Under Section E (Musculoskeletal System), Vitamin D supplement should be considered for older patients (unless in end-of-life/palliative care) in the following scenarios:

• Housebound individuals.

• Individuals experiencing falls.

• Individuals with osteopenia (Bone Mineral Density T-score between $-1.0$ and $-2.5$ at multiple sites).

FDA-Approved Indications for Vitamin D Supplementation

• Vitamin D deficiency and insufficiency.

• Osteoporosis.

• Familial Hypophosphatemia (including that associated with Fanconi syndrome).

• Hypoparathyroidism and Pseudohypoparathyroidism.

• Vitamin D-dependent Rickets.

• Patients with Chronic Kidney Disease (CKD) stages 3-4.

Vitamin Toxicity and Adverse Drug Events (ADEs)

Hypervitaminosis typically results from megadoses of Vitamins A, C, $B_{6}$, or Niacin.

Vitamin A (Retinoid)

• RDA: Males ($900\,\mu g$), Females ($700\,\mu g$), Pregnant individuals ($770\,\mu g$).

• ADE Dose: Long-term ($6$-$15$ months) administration of large dosages, specifically $1200\,\mu g/kg$ daily.

• Signs of Toxicity: Malaise, lethargy, irritability, psychiatric changes (mimicking severe depression or schizophrenic disorder), anorexia, GI distress, mild fever, and excessive sweating.

• Risk Populations: High doses are teratogenic (avoid in pregnancy). In smokers, high supplemental doses are associated with an increased risk of lung cancer.

Vitamin C (Ascorbic Acid)

• RDA: Males ($90\,mg$), Females ($75\,mg$), Smokers (add an additional $35\,mg$), Pregnant individuals ($80\,mg$).

• ADE Dose: > 3\,g daily.

• Signs of Toxicity: Gastrointestinal distress and the formation of kidney stones.

• Risk Populations: Patients with cirrhosis, gout, renal tubular acidosis, or paroxysmal nocturnal hemoglobinuria.

Vitamin E

• RDA: Males and Females ($15\,mg$), Pregnancy ($15\,mg$ of $\alpha$-tocopherol).

• ADE Dose: $\ge 400\,\text{units}$ daily for > 1 year.

• Signs of Toxicity: Increase in all-cause mortality.

• Risk Populations: Smokers.

Micronutrient Deficiencies in Specific Therapeutic Contexts

Metabolic and Bariatric Surgery (MBS)

• Guidelines (2022): MBS is recommended for individuals with a $BMI \ge 35\,kg/m^{2}$ regardless of comorbidities.

• Necessity of Supplementation: Long-term supplementation of Vitamin $B_{12}$, Iron, and Calcium is critical due to malabsorptive changes resulting from the surgery.

GLP-1 Receptor Agonist Therapy

Recent narrative reviews (Clin Obes. 2026) have identified frequent micronutrient deficits in users of GLP-1 receptor agonists:

• Vitamin D: The most common laboratory abnormality. Deficiency rates nearly double over $12$ months; average dietary intake is only about $20\%$ of recommended levels.

• Iron: Over $60\%$ of users consumed less than the estimated iron requirements.

• Calcium: More than $60\%$ of individuals had calcium intakes below recommended levels.

• Thiamine ($B_{1}$) and Cobalamin ($B_{12}$): Deficits increase over time, raising significant concerns for hematologic and neurologic consequences.

Multivitamin Use and Evidence

• General Recommendation (American Heart Association): Healthy people should not rely on supplements. There is insufficient data to suggest that taking supplements in excess of the RDA benefits healthy individuals.

• Indicated Populations for Multivitamins:

  • Individuals with a poor diet.

  • Elderly populations.

  • Vegetarians or vegans.

  • Patients with medical conditions or medications that inhibit absorption (e.g., bowel resection, bariatric surgery).

  • Individuals prone to anemia or those requiring fat-soluble vitamins and calcium.

Media Influence and Regulatory Oversight

The BMJ Study on Medical Talk Shows (2014)

Investigated "The Dr. Oz Show" and "The Doctors" to determine the quality of health recommendations.

• Methodology: Researchers evaluated $80$ randomly selected recommendations from each show.

• Dr. Oz Show Results:

  • Evidence supported: $46\%$.

  • Evidence contradicted: $15\%$.

  • No evidence found: $39\%$.

  • Average recommendations: $12$ per episode.

  • Most common advice: Dietary advice ($39\%$).

• The Doctors Results:

  • Evidence supported: $63\%$.

  • Evidence contradicted: $14\%$.

  • No evidence found: $24\%$.

  • Average recommendations: $11$ per episode.

  • Most common advice: Consult a healthcare provider ($18\%$).

• Key Findings: Potential conflicts of interest were disclosed in only $0.4\%$ of recommendations. Approximately half of the advice lacked evidence or was contradicted by high-quality evidence.

Professional and Legal Status of Dr. Oz

• Academic/Professional Standing: Despite ethical concerns, Columbia University took no academic action, citing principles of academic freedom. Dr. Oz is a board-certified surgeon (Thoracic Cardiovascular, General Surgery).

• The "Dr. Oz Effect": A term coined by Senator Claire McCaskill describing how a product featured on the show experiences a dramatic boost in sales, often followed by scam artists using deceptive ads.

• Regulatory Jurisdictions:

  • Food and Drug Administration (FDA): Regulates dietary supplement labels, package inserts, and accompanying literature.

  • Federal Trade Commission (FTC): Regulates dietary supplement advertising.